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How did you get interested in Medicinal Chemistry/Chemical Biology?
I almost randomly picked my course of study, Chemistry and Pharmaceutical Technology, in Rome, simply because the course titles sounded intriguing. Throughout my studies, I was consistently drawn to organic chemistry. A real lightbulb moment came when a professor introduced us to Nicolaou’s Classics in Total Synthesis, which genuinely inspired me. Wanting to keep chemistry applied to functional, biologically relevant molecules eventually steered me toward a synthesis-focused PhD in medicinal chemistry.
Where did you have your postdoc position?
My PhD in medicinal chemistry didn’t spark enormous inspiration, as I often felt classical med chem was a rather static discipline. I also have to admit that during my PhD, I had plenty of other interests pulling at my attention. Since I didn’t have any brilliant ideas pushing me along an academic track, I decided to join the chemical R&D department at Roche Diagnostics in Penzberg for an industry postdoc. That turned out to be a game-changer: working on bioconjugation, peptide, and oligonucleotide chemistry completely captured my imagination. Re-energized, I decided to return to academia for a second postdoc at MIT in Brad Pentelute’s lab. While I had originally planned to focus on bioconjugation reaction development, I ended up diving headfirst into the world of ultra-large synthetic peptide libraries and chemically engineered proteins.
Where are you currently working and what is your current position?
In September 2021, 5 years ago, I started as an independent group leader at Leiden University, where now I am an associate professor.
What are your current research interests?
One of the core interests of our group right now is building early-stage drug discovery platforms. I have always been fascinated by ultra-large library screening technologies like phage display and DNA-encoded libraries. However, I felt that a fully synthetic alternative could offer unique power. That is precisely what we are exploring: can we screen millions of fully synthetic, drug-like compounds all at once—without any barcodes for hit identification? Alongside platform development, we pursue target-focused programs on demanding targets that require creative, non-traditional chemical modalities to disrupt complex protein–protein or protein–nucleic acid interactions.
How would you describe yourself as a supervisor?
I try to be very involved with each group member, both personally and on a project level. It’s always about finding the right balance: fostering growth and independence, while directing the project firmly enough to achieve maximum impact—both for our program and in general. I really enjoy interacting with my group, and I feel there is still so much for me to learn as a supervisor. Whenever I meet professors I admire, I always try to pick their brains about their supervision philosophy.
Which of your papers are you most proud of and why?
When it comes to publishing, I really don’t care about volume, I only care about putting out work that I truly stand behind. That’s why I can honestly say I’m proud of every paper we've published. If I had to pick the one that made the biggest splash and shaped our future trajectory the most, it’s our paper on barcode-free hit discovery from massive libraries (Nature Communications, 2025), spearheaded by my first-generation PhD student, Edith van der Nol. The external reaction to that work really put our platform on the map and opened up the direction we’re pushing forward today.
Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?
The way things go can often be, or at least appear, unfair. I’ve experienced situations that genuinely almost ended my scientific career. Both during the transition from Master’s to PhD and from postdoc to independent PI, I went through moments that I’d definitely describe as unfair. At the same time, I’ve had unfair luck on plenty of other occasions, starting with the unfair advantage of simply growing up in a very privileged part of the world, but also further along the way. I think the best any of us can do is make the absolute most of the opportunities and talents we’ve been handed. When something unfair happens, it’s completely fine to be mad, just don’t ruminate; move on. We can’t always control everything, and looking forward is almost always the best medicine. Being grateful for the good things we do experience makes keeping that attitude a whole lot easier.
Which scientist do you admire the most and why?
That’s a long list of past and present personalities, and there’s a whole lot of variety in what I admire across different people. I couldn’t pin it down to just one thing or person. I can say that I admire some people purely for their science, while not being so sure about their personalities. Others are fantastic human role models, while some really stand out because they’ve managed to stay humble despite massive success. I think admiring others is important and really helps you grow, but it’s just as important to stay nuanced and differentiated in what you take from them.
Which field of medicinal chemistry do you consider the most promising for the future?
The pace of computational discovery right now is downright dizzying. High-throughput automated and combinatorial wet-lab experiments simply have to keep up, generating the grounded datasets needed to train better models and rapidly validate computational hits. It’s that closed loop, computational discovery paired with rapid empirical validation, that will define the next few years, adding real depth to multiparameter predictions and speeding up drug development. At the same time, I think radical bio-based modalities will continue to shake up the field, especially if intracellular delivery for biologics finally becomes broadly viable, though that's a bit outside my wheelhouse to predict with any certainty.
How did you get interested in Chemical Biology?
My passion for medicinal chemistry and chemical biology started during my Bachelor of pharmaceutical sciences at Utrecht University where I had great medicinal chemistry mentors. During that time, I discovered my passion for organic synthesis in the context of drug development. This interest has been with me ever since.
Where did you have your postdoc position?
I am currently in the fourth year of my PhD at the University of Leiden, Netherlands. The main focus of my PhD work is the development of novel chemical modalities that target G protein coupled receptors (GPCRs). Such modalities include PROTACs and covalent antagonists.
What are your current research interests?
I am currently a PhD candidate in the fourth year. My current research is focusing on discovering novel approaches for the targeted degradation of membrane proteins. My main interest in the field of medicinal chemistry and chemical biology is induced proximity. This concept brought An exciting new approach in drug discovery. Instead of antagonizing a target, we can now decide to degrade it or activate it or relocate it. With the current powerful induced proximity we have in hand and looking at the speed at which this field develops, I believe we will witness great strides in targeting difficult to treat diseases.
How would you explain what your research area is to non-scientists?
My research involves dealing with proteins located on the surface of cells. In healthy conditions, these proteins are important for the cells. However, in disease states, these proteins can contribute to worsening of these diseases. I work on developing chemical LEGOs to bring back these misbehaving proteins back to their normal state. By achieving that, we can cure different cancers, immune diseases or cardiovascular conditions.
What do you like best about your work?
What I like best about my work is that it never gets boring, we are always dealing with scientific puzzles either in the organic chemistry lab or in the pharmacology lab. These puzzles can vary from optimizing synthetic routes, purification techniques, confusing assay data or even data that we did not expect at all. These daily challenges keep me excited about the scientific research work I do during my work.
What kind of tasks does your work involve?
My daily tasks involve being in the organic chemistry lab, synthesizing the compounds that I have designed along with their workups and purification. In addition, I supervise master thesis students in the lab. Moreover, I coordinate with the researchers involved in the biological evaluation of my chemical tools. Such work involves discussing data, suggesting changes in the assay or adjusting the design of my compounds.
What kind of skills does your work require?
I would say that the skills required in my field of work are also skills that I keep improving on everyday in my work. Such skills include critical thinking, leadership, mental resilience, patience, active listening and interdisciplinary mindset.
How many PhD students and postdocs do you currently supervise?
During my PhD I was involved in the supervision of 5 master thesis students and eight bachelor thesis students. This experience provided me with extensive knowledge on teaching novel concepts or techniques to students. Furthermore, I learned how to efficiently delegate tasks. But most importantly I learned how to be a good mentor to inspire the younger generations.
How would you describe yourself as a supervisor?
I would describe myself as a quirky but serious supervisor that not just aims to teach his students but inspire them to pursue their motivations and assist them on their scientific journey.
What do you consider your greatest achievement in your scientific career?
The biggest highlight of my career so far was presenting one of my PhD projects during the EFMC-ACS medi conference in Utrecht in 2024. During the conference I gave a presentation about the work we did on the targeted degradation of GPCRs.
Which of your papers are you most proud of and why?
The paper I am most proud of is the paper I am currently writing. Sadly, I can not disclose more information about it until we submit it.
What are the features of a successful PhD student or postdoc?
I find it difficult to answer that question since I am currently a PhD student. I would say one of the pitfalls PhD students fall into is impostor syndrome (myself included). Thus, I think a successful feature of a PhD student would be great motivation combined with being realistic about the speed but also the failures of life science research.
What advice would you give to someone who wants to know more about your field?
I would say feel free to reach out to me through email or LinkedIn and I will be more than happy to provide you with an overview of the field and prominent scientists in the field that you can follow. Apart from that, connecting with scientists in the field through social media platofrms like LinkedIN is very useful to get aquainted with the field. Setting up publication alerts from journals is also a valuable tool to stay up to date with novel research.
What would you like to ask from other medicinal chemists?
I would like to ask other medicinal chemists about the chemical structure of their favourite drug candidate or which protein do they dream of one day targeting.
Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?
I would say I am grateful that I did not experience any unfair situation during my PhD. My advice if that happens to anyone in the field is to reach out to the confidential advisors within the institute to fix the situation. I can image that this approach can be daunting for some PhD students, thus I would also advise to reach out to the co workers they trust the most and seek their guidance.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
I was once working with a compound that was extremely yellow and I was loading it on the silica column, I did not realize the column was leaking and my fumehood was covered in yellow stains permanently.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
Great lighthearted YouTube organic chemistry content: extractions & Ire, chemiolis.
Great organic chemistry book: The Chemists’ Cookbook: A practical handbook of 201 named reactions for advanced students and researchers of synthetic organic by Lluís Llorens Palomo (a cool scientist that I follow on social media)
Which scientist do you admire the most and why?
The scientist I admire the most is Professor Craig Crews. I remember when I first read his papers on targeted protein degradation, I was astonished and developed a rapid and great interest in the field based on these papers. When I got to meet him in person, he was very friendly and gave me a lot of valuable advice on how to do research in this field.
I would say the same field I am interested in (could definitely be biased) which is induced proximity. I believe we are just starting to open this treasure chest full of opportunities in drug discovery that can help a lot of people suffering from incurable diseases.
What would you expect to be the next major breakthrough in medicinal chemistry?
I believe the next major breakthrough in medicinal chemistry would be a discovery in the area of biocatalysis combined with synthetic organic chemistry. Such discovery can be in the form of biocatalysts that enable common synthetic reactions involved in medicinal chemistry to be done with greener alternatives and better yields. Such discovery can enable the development or production of medicinal compounds that were once considered unachievable or too environmentally unfriendly to produce.
How did you get interested in Chemical Biology?
I began my research journey, during my master’s training, at the Institut Pasteur, in Paris, in the field of synthetic carbohydrate-based conjugate vaccines. I discovered the fascinating combination of organic chemistry and biology. This first experience deeply inspired me and motivated me to continue expanding my expertise in carbohydrate chemistry during my PhD thesis.
Where did you have your postdoc position?
University of Oxford – Organic Chemistry in the group of Prof. David Hodgson
Where are you currently working and what is your current position?
I work at UCB, in Braine l’Alleud (Belgium), as director in medicinal chemistry.
What are your current research interests?
Discovery of novel chemical entities to treat neurological disorders with a focus on epilepsy, neurodegenerative diseases, and& neuroinflammation
How would you explain what your research area is to non-scientists?
Our aim is to bring new drugs to treat patients suffering from severe neurological disorders.
What do you like best about your work?
I love the combination of exquisite science and team work to bring treatments to patients.
What kind of tasks does your work involve?
As project leader of therapeutic projects, I interact with experts from many disciplines involved in the drug discovery process. A key task is to coordinate activities across functions, making sure that the strategy is clear and activities are on track. Communication inside and outside the team is essential.
What kind of skills does your work require?
Good coordination, interpersonal relationship, team leadership, communication skills
How many PhD students and postdocs do you currently supervise?
None
How would you describe yourself as a supervisor?
I believe I’m a mix between democratic supervisor and coaching supervisor. The key is to adapt our leadership style to the level of experience and development need of each team member.
Are you currently looking for a new PhD student or a postdoc?
Not myself, but at department level, yes.
What do you consider your greatest achievement in your scientific career?
As the Associate Project Leader for the D1PAM project that led to the discovery of Glovadalen—an oral, brain-penetrant positive allosteric modulator of the dopamine D1 receptor currently in Phase 2 clinical trials. It was an incredible learning journey that enriched me both scientifically and as a leader.
Which of your papers are you most proud of and why?
‘Evaluation of 18F-UCB-H as a novel PET tracer for synaptic vesicle protein 2A in the brain’, Warnock et al., J. Nucl. Med., 2014, 8, 1336. UCB-H is widely used by many groups, as diagnostic tool to image synaptic density and in epilepsy research.What are the features of a successful PhD student or postdoc?
In my mind what a PhD thesis brings you is a rigorous mindset and great resilience. PhD and postdocs are very tough and demanding experiences, but so rewarding, ultimately. The most important is the journey.
What advice would you give to someone who wants to know more about your field?
Use the many ‘materials’ that are available on line (webinars, EFMC Best practices, …), readings and conferences/workshops. Be curious. Ask speakers if you have questions, connect… People are generally happy to help!
What would you like to ask from other medicinal chemists?
To keep an open mind and stay away from dogma.
Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?
I have been very lucky and was supported in my development. It’s important to listen to your feelings and set your own limits.I recommend to regularly take the time to pause and reflect, to question yourself about your journey.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
On my first day at work, I inadvertently push an open vial from my colleague (we were sharing a hood). The final product it was containing spilt onto the hood bench. Not a good way to start :-)
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
In addition to gaining scientific expertise, I recommend to develop leadership and interpersonal skills. Those are essential to connect people together. TED talks offer high quality presentations on so many topics. More specifically I recommend to read books/watch videos from Simon Sinek.
Which scientist do you admire the most and why?
I admire all scientists who dedicate their life to better understand the world. It requires huge resilience and great humility, as this is never ending… and that’s the beauty of science. Learning is a journey where each discovery opens the door to deeper mysteries.
Which field of medicinal chemistry do you consider the most promising for the future?
Medicinal chemistry… digitally augmented!
What would you expect to be the next major breakthrough in medicinal chemistry?
Medicinal chemistry… digitally augmented!
How did you get interested in Chemical Biology?
I have always been fascinated by topics at the interface of chemistry and biology. During my studies, I got interested in chemistry and chemical biology applied to drug development. I believe that using chemical tools to improve human health is really the most beautiful application of science, as it combines creativity, precision, and purpose with the potential to make a real difference in patients’ lives.
Where did you have your postdoc position?
After my PhD, I joined Philochem as research scientist, working in the field of tumor-targeted therapies such as antibody-cytokine fusions, small molecule-drug conjugates and radioligand therapeutics.
Where are you currently working and what is your current position?
I am Head of Research at Philochem AG, the discovery unit of the Philogen group.
What are your current research interests?
My main research interest is designing and developing new targeted therapies against cancer, to obtain drugs that are safer and more efficacious than currently approved products.
How would you explain what your research area is to non-scientists?
I work on “smart medicines” that can recognize cancer cells and deliver powerful treatments directly to them, while leaving healthy tissues largely unaffected.
What do you like best about your work?
The most rewarding part is seeing an idea grow from a concept at the bench to a therapeutic candidate that can potentially improve patients’ lives.
What kind of tasks does your work involve?
I oversee research programs, design new therapeutic strategies, guide experimental activities, and collaborate with internal and external teams, including clinical researchers to bring these compounds to patients.
What kind of skills does your work require?
Energy, precision, knowledge, passion for science, patience, vision, diplomacy…too many to be mastered, but trying is half the fun.
How many PhD students and postdocs do you currently supervise?
I am currently supervising a research team composed of 40 scientists, with PhD students, Research Associates, Research Scientists, and Senior Scientists.
How would you describe yourself as a supervisor?
I aim at being a supportive, direct and present supervisor. I love motivating good scientists and trying to get the most out of them.
Are you currently looking for a new PhD student or a postdoc?
We are always looking for talented students and postdoc to join our research team at Philochem!
What do you consider your greatest achievement in your scientific career?
I consider the discovery of OncoACP3, a new prostate cancer targeting ligand, one of the greatest achievement in my scientific career.
Which of your papers are you most proud of and why?
“Discovery of high-affinity ligands for prostatic acid phosphatase via DNA-encoded library screening enables targeted cancer therapy” by Georgiev et al. (in which I am corresponding author together with Dr. Sebastian Oehler), published in 2025 in Nature Biomedical Engineering. In this paper, we describe the discovery on new ACP3-targeting ligands by DEL technology.What are the features of a successful PhD student or postdoc?
A student which invests energy and intelligence in the project will always be a successful PhD student / post-doc!
What advice would you give to someone who wants to know more about your field?
Read literature, look at what companies are doing, go to conferences, and talk to medicinal chemists that are working in top groups (if you have the chance).
What would you like to ask from other medicinal chemists?
How do you balance creativity and risk-taking with the practical constraints of drug development?
Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?
Unfair situations happen to everyone. My advice would be to seek mentorship, build supportive networks, and don’t let setbacks define your trajectory.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
Once I mislabelled mice when doing an in vivo experiment. The compound was not showing targeting, and I was trying to explain to my colleagues that, in my opinion, the molecule was not promising.. when we realized that I picked the wrong mouse and in the right animal the test compound was showing the expected effect! We have just successfully completed a Phase I trial with the same molecule… very embarrassing..
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
Book: “Flatland: A Romance of Many Dimensions” (by E. A. Abbott)
Podcast: “The basement” (Italian podcast) / “On Purpose” by Jay Shetty
Which scientist do you admire the most and why?
I have great admiration for Prof. Dario Neri, my PhD mentor. He is an incredible source of knowledge, motivation, and ideas for new therapeutic approaches. Dario has been trained by two Nobel prize winners, Sir. Gregory Winter and Prof. Kurt Wüttrich, two scientists who I also greatly admire.
Which field of medicinal chemistry do you consider the most promising for the future?
Targeted therapies, particularly small molecule-drug conjugates hold great promise as an alternative to antibody-drug conjugates. Their potential for precision medicine is enormous.
What would you expect to be the next major breakthrough in medicinal chemistry?
I believe that the use of Artificial Intelligence applied to DNA-Encoded Chemical Libraries and affinity measurements could revolutionize the way drugs are discovered.
How did you get interested in Medicinal Chemistry?
I developed a general interest in the interface of organic chemistry, biology and pharmacology during my pharmacy undergraduate degree.This led me to seek specific post-graduate opportunities in this area, including an MSc in medicinal and biological chemistry at the University of Edinburgh, a PhD in organic chemistry at Rhodes University, and a Post-doctoral Fellowship at the University of Stellenbosch. These combined experiences as well as the opportunity to interact with students and academics across related disciplines helped me to develop my specific interests in chemical biology and medicinal chemistry.
Where are you currently working and what is your current position?
I am currently an Associate Professor of Organic Chemistry at the University of Cape Town.
What are your current research interests?
The main interest of our group is to apply skills in organic synthesis and biophysical chemistry (particularly native mass spectrometry) to investigate ‘difficult-to-access’ and underexplored chemical space. Examples of this include characterization and modulation of transient protein-protein interactions and small molecules, which are confined to the extracellular environment. The aim of this work is to develop creative solutions for addressing neglected diseases in Africa, particularly those without validated pharmacological targets. Our recent focus has been to develop small molecules which modulate the interaction between the Hsp90 chaperone protein, and its co-chaperone HOP as a strategy for developing inhibitors onco-viruses (e.g. KSHV).
What do you like best about your work?
I enjoy the open-ended nature of academic research. I always find it amazing, how curiosity-driven research projects don’t end up progressing exactly as you planned. Somehow, the process of conducting well executed experiments produces unexpected results and delivers different but equally important scientific insight.
What kind of skills does your work require?
Typically, our contributions to collaborative projects require skills in synthetic organic chemistry and /or analytical chemistry skills. Our group also place high-value on communication, teamwork and cooperation. In addition, being able to problem-solve and figure out what is going on when ‘something weird’ happens is very important.
What do you consider your greatest achievement in your scientific career?
A few years back I was the recipient of a Royal Society Future Leaders – African Independent Research (FLAIR) Fellowship. This fellowship acted like a springboard for advancing my science and my career in general.
Which of your papers are you most proud of and why?
These would have to be the series we published on the Hsp90-HOP PPI, where we developed native mass spectrometry methods to identify PPI modulatory compounds, and further developed these to facilitate PPI interfacial characterisation. This led to a very satisfying translational result, where we demonstrated that our Hsp90-HOP PPI inhibitory compounds disrupted the activation of KSHV lytic replication, thus providing the first potential validation of this PPI as a host-based target for KSHV drug discovery. From a basic sciences perspective, it represented an important step in understanding viral interactions with the host regulatory machinery and is a key idea we are taking forward into our future chemical biology programme.
What are the features of a successful PhD student or postdoc?
Unfortunately, failure is a big part of research. Students and post-docs who are not closed books, but to seek help when it is needed, communicate success and failure to their advisors regularly and understand that failure is not a reflection on them personally, tend to be more successful.
What advice would you give to someone who wants to know more about your field?
Join the EFMC mailing list!
What would you like to ask from other medicinal chemists?
Please keep in mind that insightful science is still achievable using ‘old-school’ approaches. Particularly in resource constrained environments. Judge the actual science, not the perception.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
I really enjoy the Naked Scientists Podcast. They are experts in distilling the essence of cutting-edge science and keeps me abreast of many different fields.
Which scientist do you admire the most and why?
Aaron Klug, and not just because he is South African. His ability to harness insights in fundamental chemistry and physics to study viral structure, is for me the essence of chemical biology.
Which field of medicinal chemistry do you consider the most promising for the future?
Medicinal chemistry and chemical biology together have made some outstanding dogma breaking progress in the last two decades. Introducing covalent warheads and the large non ‘drug-like’ molecules for proximity-based pharmacology are two particular successes. I think this dogma breaking trend will continue into host-based targets for antimicrobial drug discovery for numerous infectious pathogens.
What would you expect to be the next major breakthrough in medicinal chemistry?
The role of drug design in personalised medicine will be fascinating to follow.
How did you get interested in Medicinal Chemistry?
During my university studies in Chemistry, my early interest in (Bio)Organic Chemistry led me to pursue a PhD in synthetic organic chemistry in the field of carbohydrates. The group had a strong focus on nucleosides and nucleotides, and my project centred around synthetic methods to produce phosphorylated sugars in a highly controlled manner. These structures are found, for instance, on the surface of parasites that cause divers pathologies, and they may have potential in vaccine development. Building on the chemical synthesis skills I had developed during this time, I then moved into the field of antiviral nucleotides for my postdoc. There, I expanded my skillset and got the opportunity to evaluate the compounds I had synthesized in cell-based infection models. It has always been my interest to truly work at the interface of chemistry and biology, and the idea to drive pharmaceutical innovation is a great motivation. I am deeply thankful for the opportunities that I got during these early steps of my career which I consider a great privilege.
What are your current research interests?
With my background in Chemistry and my experience in cell-based assays, my current work encompasses the development of innovative assays and screening, as well as compound library design and the continuous development of our small molecule screening collection for various drug discovery projects at Fraunhofer ITMP.
To be more specific, my main projects evolve around new drug modalities. Targeted protein degradation, for instance, is a novel pharmaceutical paradigm that promises to overcome some of the critical limitations of traditional drugs. Unlike the classical enzyme inhibitors or receptor (ant)agonists, small molecule degraders don’t modulate the biochemical function of their target protein but instead, they induce a “chemical knock-down”. This means that upon degrader treatment, the target protein is depleted. Thus, the effect reaches beyond blocking, e.g., an enzymatic activity, and covers protein scaffolding functions etc.
Regarding my work environment, the Fraunhofer-Gesellschaft is Europe’s leading applied research organization and has ~75 institutes covering diverse areas in research and engineering. We typically team up with academics and companies in projects to facilitate the translation of basic research findings into innovative technologies. Having been trained in Chemistry and Biology, I continue to expand my knowledge-base by closely working with Cheminformaticians and Data Scientists. Additionally, I greatly enjoy working with academics as well as the industry sector and contributing to the innovation process at this critical intersection.
What do you consider your greatest achievement in your scientific career?
Generally, I find it hard to rank. Of course, there are obvious achievements, and I am proud and thankful to have been awarded generous prizes and prestigious grants. But of no less importance for me are the less visible - or less measurable - achievements: I feel highly rewarded by mentoring young scientists during part of their journey and seeing them push forward and thrive in their career.
Overall, and at the complete danger of sounding all too cliché, I consider science a team sport and I am highly motivated by the process of “doing science”, achieving goals and celebrating the wins as a team.
What advice would you give to someone who wants to know more about your field?
Depending on your background – and personal preference – one possible resource might be the Dana-Farber Targeted Protein Degradation webinar series, that you can follow on their YouTube channel. The Ciulli lab at the Centre for Targeted Protein Degradation (CeTPD) in Dundee publishes a Journal Club that you can access openly via their website and that is intended for the wider scientific community. Both resources, and there surely are many more options, may give you an idea of important or recent work in the field and you could take it from there to dig into the primary literature.
What is the most embarrassing thing you have done in the lab while doing experiments?
Well, there might have been once a very small-scale fire during the quenching of some very minor amount of residual sodium hydride… But again, and I’m not getting tired of this: science – and lab work – is a team sport and I have been lucky to work in great teams where during such a (did I say very small-scale?) lab accident there were immediately great colleagues by my side giving a helping hand (with a bucket of sand).
Which field of medicinal chemistry do you consider the most promising for the future?
Novel drug modalities. Yes, I am biased. But I also truly believe that to achieve the goal of modulating biology beyond what is possible now – i.e., therapeutic innovation - requires to expand into novel mechanisms. Exciting examples are proximity-inducing compounds or RNA-targeted therapeutics.
How did you get interested in Chemical Biology?
I have always been fascinated by the power of chemistry in probing and modulating fundamental biological processes relevant to human health and disease. In my doctoral studies at ETH Zürich in the group of Prof. Erick Carreira, I utilized strategies rooted in total synthesis to develop chemical probes for cannabinoid receptors. I obtained my Ph.D. in 2021 and joined the lab of Prof. Nathanael Gray at Stanford University as an SNSF Postdoctoral Fellow the same year. My postdoctoral work focused on the development of chemical inducers of proximity for context-specific gene modulation.
Where are you currently working and what is your current position?
I am currently transitioning from my Postdoc at Stanford to starting my own research group as a Max Planck Group Leader in Heidelberg, Germany, in January 2025. My lab will develop chemical inducers of proximity that induce new protein-protein interactions to rewire disease drivers and activate therapeutic signaling. A particular focus will be on molecules that re-localize epigenetic activators and transcription factors on chromatin to enable selective activation of therapeutic genes without the need for genetically altered cells and organisms. I envision these molecules to serve both as chemical probes and as a basis for new therapeutic strategies.
If you are intrigued to work in chemically induced proximity, appreciate interdisciplinarity and collaboration, and have a background in chemistry, pharmacology, or molecular biology, please get in touch!
What do you consider your greatest achievement in your scientific career?
At Stanford I have been fortunate to work on bivalent molecules that turn kinase inhibitors into context-specific activators of cell death in cancer cells. Looking back, this was a risky endeavor that paid off and now opens many venues in which kinase inhibitors may be used for new therapeutic applications beyond that of target-centric silencing of catalytic activity.
What is further gratifying about this work is that it inspired the foundation of a new biotechnology startup company in the San Francisco Bay Area, which aims to develop the molecules into new precision therapies for cancer patients.
What are the feaures of a successful PhD student or postdoc?
“Never talk yourself out of an experiment” is advice from my PhD advisor that keeps on paying dividends. Science is experimental, and I have seen it time and time again that fortune does indeed favor the bold. Another one, slightly adapted from my Postdoc mentor in California that applies to any career stage: ”A good academic always has a good tan and a plan B.”
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
The weekly ‘Targeted Protein Degradation’ webinar, hosted by the Dana-Farber Cancer Institute, is a must watch for all aficionados of chemically induced proximity. In terms of books, I have greatly enjoyed reading ‘The Emperor of all Maladies’ by Siddhartha Mukherjee and ‘Dark Remedy’ on the history of the notorious thalidomide.
Which field of medicinal chemistry do you consider the most promising for the future?
I think what makes the present so exciting for us working in chemical biology and medicinal chemistry is that, by working across disciplines and the academic-industry boundary, we are rapidly discovering new chemical strategies for addressing previously challenging drug targets and diseases.
Admitting a little bias, I trust chemically induced proximity will continue to be playing a leading role in “drugging the undruggable”. The developments in targeted protein degradation, the most established instance of induced proximity, serve as impressive example – and yet it barely scratches the surface of what is possible!
How did you get interested in Medicinal Chemistry?
During my studies in pharmaceutical sciences, I was quickly fascinated by how protein and small molecules interact and how we could rationally optimize a compound to fit into a protein cavity. This drew me to join a medicinal chemistry lab as soon as I had the opportunity to do so.
Where and when did you obtain your PhD diploma?
I obtained my PhD in 2020 from the Catholic University of Louvain (UCLouvain, Belgium). I worked in both a pharmacology lab (Pr. P. Sonveaux) and a medicinal chemistry lab (Pr. R. Frédérick). During my doctoral studies, I became particularly interested in biophysical and biochemical assays and how they can allow scientists to probe interactions.
What was the topic of your PhD project?
During my PhD, I designed peptidic tool compounds able to target the tetramerization of lactate dehydrogenase (LDH), a target for cancer therapy. The main part of my PhD was to successfully set up a panel of biochemical and biophysical assays allowing to study LDH tetramerization process. These assays were essential to help us understand how the tool compounds were working, and to optimize their potency.
Where did you have your postdoc position?
Following the completion of my PhD, I remained a year as a postdoctoral researcher in the laboratories where I conducted my doctoral research. During that year, I focused on adapting the assays I had developed during my PhD to the discovery of small molecules that could potentially interfere with LDH tetramerization.
Afterwards, I took on a second yearly postdoctoral position at the Institute of Cancer Research in London, UK, under the guidance of Dr. M. Douglas. During this period, I studied recombinant heteromeric complexes involved in DNA replication. This research involved a range of techniques and approaches in biochemistry and molecular biology. This second postdoc gave me the opportunity to expand my skillset and broaden my research experience.
After my postdoc in London, I decided to transition to industry and started working as a scientist specialist in biophysics at Galapagos, an integrated drug discovery company based in Belgium.
What are your current research interests?
I am fascinated by the current biophysical and biochemical technologies that enable scientists to study the most complex interactions. I am also excited about new paradigms in drug discovery, such as protein degraders, stabilizers, and destabilizers.
How would you explain what your research area is to non-scientists?
My work involves developing new methods to understand how different chemical compounds interact with their target. By studying these interactions, we can gain insights into how different compounds work and potentially identify new treatments for diseases. This is particularly important for developing new drugs, as it helps us understand how a drug might work in the body and how it can be optimized to be more effective.
What do you like best about your work?
I really enjoy the freedom to be creative and find new ways to interrogate the different targets we are working on. I'm always learning new things and trying new approaches, which keeps the work exciting.
What kind of skills does your work require?
My work involves a lot of experimentation in the lab, where I use a variety of skills related to biophysics, biochemistry, molecular biology, and protein biochemistry. I am responsible for designing and executing experiments, analysing data, and presenting my findings in a way that makes sense to both technical and non-technical people.
Which of your papers are you most proud of and why?
I am proud of my first paper as first author in the Journal of Medicinal Chemistry. It was a challenge to get it accepted, but I was happy and relieved when we received the acceptance letter. This research also led to the development of two patents that are currently being utilized by a pharmaceutical company. I find it highly rewarding and motivating to see the direct impact of my work on practical applications.
What are the features of a successful PhD student or postdoc?
In my opinion, pursuing a PhD requires a great deal of resilience and a willingness to step outside of your comfort zone to acquire new skills. It's important to keep in mind that a PhD programme is a unique opportunity to learn and develop skills, as you may not have as much time for learning later in your career.
What advice would you give to someone who wants to know more about your field?
Ask around! Scientists are always eager to share their passion and will often enjoy helping and guiding new people in the field. Going to conferences/congress is also a good way to get new ideas and meet members of the scientific community working on similar topics.
Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?
While I have not personally experienced unfair situations, I have witnessed many of them during my PhD. I would advise scientists who are facing such situations to remember that their worth is not defined by the discrimination they may face. Remember that there is always a place where you can feel valued and have opportunities to grow.
Which field of medicinal chemistry do you consider the most promising for the future?
It is difficult to choose from the numerous avenues that are currently being developed, but I would say that I am especially excited about bifunctional molecules such as PROTACs. In my opinion, such molecules open new possibilities beyond the classical inhibition/activation of a target. They have the potential to revolutionize what we consider a druggable target.
How did you get interested in Medicinal Chemistry?
As I wrote in my very recently published scientific autobiography in the Serie Lives in Chemistry (https://l-i-c.org/horst-kessler.html), I was trained as Organic Chemist (synthesis of small ring compounds) at the University of Tübingen under the guidance of Eugen Müller in my Ph.D. After my thesis I studied rapid intramolecular rearrangements by NMR-spectroscopy. After habilitation I obtained a call to the Johann-Wolfgang-Goethe-University in Frankfurt as Full-Professor at the age of 31 years.
There I became interested in peptide synthesis and conformational studies by NMR. After 18 years in Frankfurt I moved as professor of Organic Chemistry and Biochemistry to the Technical University Munich (TUM). We developed a number of novel multidimensional NMR techniques in combination with molecular dynamics to achieve reliable pictures of peptide conformations. This knowledge was used to design biological active conformationally restrained peptides with super-activities and receptor subtype selectivity.
My interest shifted to application of those peptides as drugs of for molecular imaging (after radiolabeling for SPECT and PET). Finally my main interest was in the design of orally active peptides (via conformational restraints and multiple N-methylation.
Where are you currently working and what is your current position?
After my official retirement in 2008, I became a member of the IAS and member of the Senior Excellence Faculty and was granted to do lab work until 2019.
My main interest was the development of super-active and selective ligands for RGD-recognizing the cell-adhesion receptors, the integrins. We were able to develop (in our opinion the ligands with highes affinities (sub-nanomolecular) and very high selectivities (several orders of magnitude) against other integrin subtypes (for αvβ3, αvβ6, αvβ8, α5β1 and αIIbβ3). Some of these ligands are now used in the clinics are in clinical phase I – III, e.g. for the detection of cancer (see trivehexin for αvβ6 or pentixafor for the the chemokine CXCR4).
My general interest was the modification of bioactive peptides in compound for medical use. For this we introduced very early the concept of conformational restraint and used it under conformational control by NMR. Peptidic drugs should be at best orally available. In some cases it was possible to pin down the essentials for oral availability.
I am over 83 years old and am retired.
What do you consider your greatest achievement in your scientific career?
How did you get interested in Medicinal Chemistry?
I studied chemistry and while I enjoy organic chemistry and synthesizing compounds, my most motivation relies on knowing that the compounds we make could be useful to treat diseases. I performed my PhD studies at the Medicinal Chemistry institute from CSIC in Madrid, under the supervision of Dr. Ana Martinez and Dr. Carmen Gil from 2008 to 2012, where I developed compounds that were able to protect neurons from toxic insults and promote neurogenesis to create new neurons. Afterwards, I did my postdoc at The Scripps Research Institute in La Jolla, US, under the supervision of Dr. Phil Dawson, working on peptides and Quantum Dots.
Where are you currently working and what is your current position?
Currenlty I am the head of the lab Biosensors in Neuroscience at IMDEA Nanoscience. We are working on developing sensors that allow us to efficiently select future drugs for neurodegenerative diseases that protect neurons and improve their homeostasis in models of neurodegeneration. In addition, we work in the development of multifunctional drugs.
How would you explain what your research area is to non-scientists?
We try to understand whether a drug will protect damaged neurons in neurodegenerative diseases and could ultimately stop or slow down neurodegeneration.
What kind of tasks does your work involve?
I supervise my students, help them make the experiments work and analyse with them the data. A lot of my work consists in writing, from reports to grant proposal to publications and posters. I also spend a considerable time preparing and giving talk and seminars and finally I try to keep up with the recent literature in my area.
How many PhD students and postdocs do you currently supervise?
I currently supervise 4 PhD students, 1 master student and 1 undergrad.
Are you currently looking for a new PhD student or a postdoc?
Yes! I am looking for a PhD student to work in a Doctoral Network (TClock4AD) and a Postdoc, as part of the Ideal postdoctoral call from IMDEA Nanociencia.
How would you describe yourself as a supervisor?
I try to guide my students as best as I can, showing them how to properly design and perform experiments and giving them solutions when things fail. Also I try to make a friendly environment in the lab, we have group meeting every week with pastries and make a fun activity every year together. A PI does not only need to be a valuable scientist knowing how to design experiments and analyse them but also you need to be able to manage people and projects that make the whole research group function.
What do you consider your greatest achievement in your scientific career?
I believe my achievements are related to using chemical tools to tackle complex aspects of biology such as understanding the role of GSK-3 enzyme in neurodegenerative diseases, that was discovered through the synthesis of chemically and biologically diverse inhibitors, or the use of dynamic sensors to understand key biological processes.
Which of your papers are you most proud of and why?
I am particularly proud of the development of multitarget compounds against Alzheimer’s disease (Angew. Chem.2021, 60, 19344) in which not only we discovered promising compounds but we used in situ click chemistry with BACE1 as a template.
What are the features of a successful PhD student or postdoc?
Curious, hard-working, innovative and meticulous. I have to say that maybe one does not excel at all of those but if they are not imperative, just know and exploit your strengths and work on your weaknesses!
What advice would you give to someone who wants to know more about your field?
There are plenty of learning resources and outreach activities organised for example from my research centre, IMDEA Nanociencia. Come to any of those and we would love to explain our science to you.
Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?
Sometimes the rejection of a grant or paper is difficult but if you believe in the project, keep on improving it and working hard and results will come. Also not everything is about the prestige of journals or awards, it is more important to be a good supervisor and train new good scientists for tomorrow’s problems. Finally we live in a very competitive world and with many talented scientists, and sometimes it is overwhelming if you do not achieve everything your colleagues do. Here I would say that keep on working, believe in yourself and keep up the good work. Results will come naturally and we don’t need to be obsessed with them but with doing the best we can as scientists.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
I have had to extract the rotavap water and purify again a compound after droping it there….
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
I recommend the books from María Dueñas, I love In the Pipeline blog from Derek Lowe and I am a fan of tiny desk concerts.
Which scientist do you admire the most and why?
I admire many, especially the ones I collaborate with now, the ones that have trained and supervised me and those that have given me opportunities during my career. And to name a well-recognized researcher I will say I admire Rafael Yuste, one of the initiators of the brain initiative, that not only works towards the progress of neuroscience but also to protect human rights.
Which field of medicinal chemistry do you consider the most promising for the future?
I am fascinated about Protacs and am excited to see what they can achieve in the clinic. In addition, I also believe multitarget drugs are highly promising for the treatment of complex diseases specially when they process a synergistic targeting different pathways.
What would you expect to be the next major breakthrough in medicinal chemistry?
Another fascinating therapeutic approach in central nervous system diseases is targeting our microbiome. The connexion it seems to have with neurodegenerative diseases is fascinating and I am sure we will see nice discoveries in this area.
How did you get interested in Chemical Biology?
Early on in my chemistry studies I became intrigued by the synthetic potential of enzymes and our budding capability to engineer them into even more useful catalysts.
Where and when did you obtain your PhD diploma?
I obtained my PhD diploma from ETH Zurich in 2011 with Professor Donald Hilvert. I worked on the “Directed Evolution of Artificial Enzymes”: Using an in silico designed enzyme as a starting point, we evolved the new-to-nature biocatalyst to exhibit “natural” enzyme-like activity.
After my PhD, I started to work in industry (Firmenich SA) and led a laboratory for biocatalytic transformations to obtain fragrance and flavour compounds.
Where are you currently working and what is your current position?
I’m a Professor at the Zurich University of Applied Sciences and lead the Competence Center for Biocatalysis (www.zhaw.ch/ccbio) where we work on engineering enzymes for challenging chemistries (e.g., stereocontrolled halogenation) and developing new enzyme engineering techniques.
How would you explain what your research area is to non-scientists?
Enzymes are Nature’s catalysts and drive chemical processes in all living things. Enzymes possess many desirable characteristics: they are highly specific, work in water, are biodegradable and can be produced sustainably.
Nature has optimized enzymes for their tasks over many billions of years and found solutions to highly complex problems. Our goal is to tailor the biocatalysts to address challenges in the chemical industry, e.g., the sustainable production of drugs, flavours, or agrochemicals.
In a way, the development of a biocatalytic reaction can be compared to top-level sports. In a first step, one scouts for talent – in our lab that means to identify wildtype enzymes that are in principle capable of catalysing the desired reaction. Next comes training: In our case, this corresponds to the directed evolution of enzymes through recurrent cycles of diversification and selection in the laboratory. Finally, we develop a “game strategy” for the tailored biocatalysts by optimizing reaction parameters such as temperature, pH, substrate, and solvent concentrations.
What do you like best about your work?
The freedom to constantly learn and discover new things leading to wonderful “Heureka” moments.
How many PhD students and postdocs do you currently supervise?
Currently, we are a team of 6 PhD students & 10 postdocs/ research associates; We are always happy to welcome new enzyme enthusiasts to our team. Currently, we are looking for a bioinformatician and a biocatalysis postdoc.
How would you describe yourself as a supervisor?
Curious, excitable, willing to listen and learn.
What do you consider your greatest achievement in your scientific career?
I am proud of developing enzymes which find meaningful practical applications.
Which of your papers are you most proud of and why?
J. Büchler, S. Honda Malca, D. Patsch, M. Voss, N. Turner, U. Bornscheuer, O. Alleman, C. Le Chapelain, A. Lumbroso, O. Loiseleur and R. Buller, Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens, Nat Commun 2022, 13, 371.
The paper highlights how elegantly enzymes can do very complex chemistry.
M. Eichenberger*, S. Hüppi*, D. Patsch*, N. Aeberli, R. Berweger, S. Dossenbach, E. Eichhorn, F. Flachsmann, L. Hortencio, F. Voirol, S. Vollenweider, U. Bornscheuer and R. Buller, Asymmetric Cation-Olefin Monocyclization by Engineered Squalene-Hopene Cyclases, Angew Chem Int Ed2021, 60, 26080 – 26086.
Leveraging our understanding of the enzymatic mechanism, we employed substrate engineering to access the desired product enantiomer.
What are the features of a successful PhD student or postdoc?
Curiosity, drive, resilience, and passion for science.
What advice would you give to someone who wants to know more about your field?
Attending conferences and getting in touch with experts in the field. I feel that interdisciplinary discussions are the most rewarding!
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
The most embarrassing experience was during my diploma thesis: When plating bacterial cells next to a Bunsen burner I set a bit of my hair on fire. I looked funny for the rest of the semester.
What would you expect to be the next major breakthrough in chemical biology?
How did you get interested in Chemical Biology?
I got fascinated about chemical biology when realizing that (i) we don’t know the molecular mechanism of action of many approved drugs and (ii) many drugs are non-selective and in fact block different proteins and associated pathways. To me, this was absolutely stunning.
What was the topic of your PhD project? Where and when did you obtain your PhD diploma?
I conducted my PhD studies at CeMM under the supervision of Prof. Giulio Superti-Furga, mostly focusing on chemical proteomics, functional genomics as well as drug combination studies to understand the mechanism of action of anti-cancer drugs. For my postdoc, I worked with Jay Bradner at the Dana Farber Cancer institute. This is when I fell in love with the paradigm of targeted protein degradation.
Where are you currently working and what is your current position?
I am currently a principal investigator at CeMM where I lead a multi-disciplinary research team of 12 scientists working in chemistry, molecular biology, and bioinformatics.
What are your current research interests?
We are excited about the concept of “chemical neomorphs” or, in other words, small molecules that allow us to endow a target protein with a novel function. This includes target protein degradation via PROTACS and molecular glues where we functionally reprogram E3 ubiquitin ligases to induce the degradation of disease-relevant proteins. But increasingly, it also goes beyond that.
What kind of tasks does your work involve?
Unfortunately, I don’t find the time to do experiments anymore. Hence, most of my tasks are around communicating, brainstorming, and organizing our research. Thinking about a scientific problem and discussing it with my students and postdocs is what I like best. Of course, it also includes presentations at meetings and conferences, and writing research grants.
How many PhD students and postdocs do you currently supervise? Are you currently looking for a new PhD student or a postdoc?
7 postdocs and 4 students. We are always excited for curious and courageous people that want to work in our team.
How would you describe yourself as a supervisor?
I think I am very approachable and easy to excite and, hopefully, empathic. However, I think I am also somewhat demanding but try to ignite intrinsic motivation rather than applying external pressure.
What are the features of a successful PhD student or postdoc?
You need to love what you are doing, and you need to constantly check if you are asking the right/most interesting questions. Talk to your peers. Get them excited. Don’t be afraid to cross scientific boundaries and involve different disciplines. Dream big and be resilient.
What do you consider your greatest achievement in your scientific career?
My postdoctoral work (Winter, Buckley et al. Science 2015) where we could show, for the first time, in vivo degradation of a protein via an all-chemical degrader is probably the most influential work (>1200 citations).
Which of your papers are you most proud of and why?
Among others, the following come to mind:
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
I once ordered a large flask of ethanethiol and opened it outside the fume hood. We had to evacuate the lab due to the horrific smell.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
I enjoyed reading “empire of pain”, telling the shocking story of the Sackler family, Purdue Pharma and OxyContin. I also loved “for blood and money”, a book that details the fascinating development of the clinically highly successful BTK inhibitors.
What would you expect to be the next major breakthrough in medicinal chemistry?
Proximity-inducing small molecules. I am convinced that targeted protein degradation is just chapter one. We will find more and more strategies to rationally rewire biological circuits and I think we will witness a convergence of chemical biology and synthetic biology. Of course, aspects of that will be critically empowered by artificial intelligence and machine learning.
How did you get interested in Medicinal Chemistry?
I became interested in medicinal chemistry during my undergraduate studies in Biotechnology (National University of Rosario, Argentina), where I was fascinated by the potential for chemistry to address important problems in healthcare. As I learned more about the role of chemistry in drug discovery and development, I became increasingly interested in the interdisciplinary nature of medicinal chemistry and the potential for collaboration between chemists, biologists, and clinicians to develop new therapies.
My passion for medicinal chemistry continued to grow during my graduate studies, where I had the opportunity to work on a project focused on the design and synthesis of novel small molecules for the treatment of neglected tropical diseases (NTDs), such as leishmaniasis, Chagas disease, HAT, malaria, etc., as well as for cancer. This experience solidified my interest in drug discovery and showed me the potential impact that medicinal chemistry research can have on patients' lives.
Since then, I have been fortunate to have the opportunity to work on a range of projects in medicinal chemistry and chemical biology, from designing inhibitors of infectious disease targets to developing novel chemical probes for target discovery in NTDs. The diversity of these projects has allowed me to develop a broad perspective on the field and has reinforced my passion for using chemistry to address important problems in healthcare.
What was the topic of your PhD project?
My interest in prenylated compounds, a privileged structure in nature, together with the enormous experience of my supervisor in the prenylated’s world, Prof Guillermo Labadie, led me to pursue a PhD focused on using these compounds as a basis for generating novel chemical and biological tools to expand our understanding of foundational biology, particularly regarding organisms that produce neglected tropical diseases (NTDs). Through my research, I aimed to develop new strategies for identifying and targeting NTD-producing organisms, which pose a significant public health threat in many parts of the world.
My PhD thesis was completed in 2015 at National University of Rosario, and was recognized and awarded by the Argentine Society of Organic Chemistry as the best Argentine thesis of the biennium (2015-2016). This recognition was a testament to the innovative approach and significant contributions of my research, which has the potential to drive new discoveries in the field of medicinal chemistry.
My first postdoctoral experience was in Argentina, working at the Rosario Chemistry Institute and the Institute of Molecular and Cellular Biology of Rosario. My second postdoctoral position was at the Department of Chemistry of Durham University, in the United Kingdom.
Where are you currently working and are your current research interests?
Currently, I am working at Durham University (United Kingdom) as a Research Fellow (Marie Sk''.chr('322').''odowska–Curie actions, Durham University, and the Network for Neglected Tropical Diseases).
My current research interests focus on the use of activity-based protein profiling (ABPP) to develop new strategies for identifying and targeting enzymes involved in the pathogenesis of neglected tropical diseases (NTDs). ABPP is a powerful chemoproteomic tool that allows us to selectively visualize and measure the activity of enzymes within complex biological systems, providing valuable insights into the mechanisms underlying disease.
My research in this area aims to expand our understanding of the molecular mechanisms driving NTD pathogenesis, with the ultimate goal of identifying new therapeutic targets and developing more effective treatments for these devastating diseases. I am particularly interested in exploring the use of ABPP in combination with other technologies, such as high-throughput screening and medicinal chemistry, to accelerate the discovery and development of new drugs for NTDs.
How would you explain what your research area is to non-scientists?
My research area focuses on studying diseases that are often overlooked and underfunded, called neglected tropical diseases (NTDs). These diseases affect more than 1 billion of people in low-income countries and can cause a lot of suffering and disability.
To help find better treatments for NTDs, I use a special technique called activity-based protein profiling (ABPP), which allows me to study the specific proteins in the pathogens that are involved in causing these diseases. By understanding how these proteins work and interact with each other (this is called the interactome), we can identify new ways to stop the disease from progressing and develop more effective drugs.
To help explain my research approach, I often use the analogy of archery. Just as an archer uses a bow and arrow to hit a target, I use specialized techniques and chemical probes to study proteins in the body that are involved in disease. In this analogy, the bow represents the various techniques I use, such as activity-based protein profiling (ABPP), while the arrow represents the chemical probes that I use to target specific proteins of interest. The target itself represents the sum of all the proteins in an organism, and the centre of the target is the specific proteins that I want to study. Just as an archer aims for the centre of the target, I aim to use my techniques and chemical probes to study the proteins that are most relevant to disease. By hitting these targets, I can gain a better understanding of the mechanisms behind disease and identify new ways to develop more effective treatments.
What do you like best about your work?
As many scientists in the field of medicinal chemistry, I enjoy the opportunity to make a meaningful impact on human health by developing new treatments for diseases that can have a major impact on people's lives. This sense of purpose and contribution to society can be incredibly rewarding.
Additionally, I enjoy the intellectual challenge and creativity that comes with designing new chemical compounds and developing innovative approaches to studying disease. There is always more to learn and discover in this field, which can make for a stimulating and engaging work environment. Also, I am grateful for the collaborative nature of the work, which often involves working with other scientists and researchers across different disciplines to tackle complex problems. The opportunity to work with others who are passionate about advancing scientific knowledge can be a fulfilling and motivating experience.
Of course, collaborating with other scientists and networking is also critical to successful research in this field. Finally, writing reports and publications and supervising PhD and Master students are important aspects of communicating research findings and mentoring the next generation of scientists.
What do you consider your greatest achievement in your scientific career?
It can be difficult to pinpoint a single greatest achievement in my scientific career. While I have received individual awards that I am proud of, I would say that one of the most fulfilling experiences was the day my first master's student, Dr. Jaime Isern, obtained his degree. Being able to train and mentor the next generation of scientists is incredibly inspiring and rewarding. It's exciting to see my students grow and develop their own research interests, and I feel a sense of pride and satisfaction in their accomplishments. Ultimately, they will carry on the work and push the boundaries of scientific discovery even further, and I am honoured to have played a part in their journey.
Which of your papers are you most proud of and why?
One of the papers that I am most proud of is "Discovery of Leishmania Druggable Serine Proteases by Activity-Based Protein Profiling," which was published in Frontiers in Pharmacology in 2022. This paper is particularly meaningful to me because it represents the first of a series of publications that will highlight the use of chemoproteomic tools in NTD-producing parasites, a project that I am currently leading at Durham University. Through this research, we are exploring new ways to identify and target the proteins that are responsible for causing diseases like leishmaniasis, and I am excited about the potential impact that our work could have on global health.
Porta, E.O.J., Isern, J.A., Kalesh, K., Steel, P.G. 2022. Discovery of Leishmania Druggable Serine Proteases by Activity-Based Protein Profiling. Front Pharmacol. 13, 929493. doi: 10.3389/fphar.2022.929493.
What are the features of a successful PhD student or postdoc?
PhD students and postdocs need to be self-motivated and have a strong work ethic to be successful. They need to be able to work independently and manage their time effectively. Another key feature is critical thinking and problem-solving skills, adaptability, and resilience. Also, a clear communication of ideas, results, and challenges is essential to succeed as a PhD student or postdoc. PhD students and postdocs often work as part of a larger research group, so the ability to work effectively in a team is critical for the sharing of ideas, knowledge, and resources to accomplish research goals. Finally, a love for science and a genuine curiosity about the world are key ingredients for success in a PhD program or postdoc position.
What advice would you give to someone who wants to know more about your field?
If someone wants to know more about my field, I would suggest several things: Start by reading review articles and textbooks on medicinal chemistry to gain a solid foundation of the field's principles and techniques. Attend conferences, workshops, and seminars to learn about the latest research and network with other scientists. Consider pursuing an internship or research experience in a medicinal chemistry lab to gain hands-on experience with the techniques and methods used in the field. Join professional organizations and subscribe to relevant journals to stay up-to-date on the latest research and news in the field. Finally, be curious and ask questions! The field of medicinal chemistry is constantly evolving, and there is always something new to learn.
Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?
Unfortunately, unfair situations can occur in any career, including scientific research. However, if a scientist is facing an unfair situation, my advice would be to first seek support from colleagues or mentors or institutional resource, and document the situation as much as possible. It may also be helpful to reach out to relevant professional organizations or advocacy groups for guidance and resources. It is important to remember that addressing unfair situations can take time and persistence, but seeking help and speaking out can ultimately lead to positive change. I have personally witnessed and experienced unfair situations in my scientific career, and I believe it is important to seek guidance and support in such situations.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
When I first started working in a laboratory, in my very first day, I accidentally broke a mortar. But it taught me a valuable lesson - that mistakes and accidents are an inherent part of the scientific process and that it's often through failure that we learn the most. As a result, I've always believed that if you're not breaking something in the lab, you're probably not pushing the boundaries of what's possible.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
Films: Radioactive; Breaking bad (series); Perfume, the Story of a Murderer.
Books: The Disappearing Spoon: And Other True Tales of Madness, Love, and the History of the World from the Periodic Table of the Elements by Sam Kean; H2O: A Biography of Water by Phillip Ball; Vector by Robin Cook.
Which scientist do you admire the most and why?
There are many scientists who have made significant contributions to the field of medicinal chemistry, and it is difficult to choose just one. However, if I had to pick, I would say Carolyn Bertozzi, because she is a renowned chemist and biochemist who has made significant contributions to the fields of chemical biology and glycobiology. I admire her not only for her ground-breaking research but also for her commitment to promoting diversity and inclusion in science. As a leader in her field, she has inspired many young scientists to pursue careers in STEM and has worked to create opportunities for underrepresented groups in academia. Her dedication to interdisciplinary research and her ability to combine chemistry, biology, and medicine in innovative ways is truly remarkable, and I am inspired by her work and her vision for the future of science.
Which field of medicinal chemistry do you consider the most promising for the future?
Currently, there are several exciting areas in medicinal chemistry that show great potential for future developments. Some of the most promising fields of medicinal chemistry for the future include the development of targeted therapies for cancer and other diseases, the discovery of novel antibiotics and antiviral drugs to combat emerging infectious diseases, the design of new drugs for neurological disorders, proteolysis targeting chimera (PROTAC), nanotechnology-based drug delivery systems, and the development of personalized medicine approaches based on genomics and proteomics. They are all promising areas that could have a significant impact on human health in the future. Additionally, the use of artificial intelligence and machine learning in medicinal chemistry is also a rapidly growing area that holds great promise for accelerating drug discovery and development.
What would you expect to be the next major breakthrough in medicinal chemistry?
I would say that personalized medicine is one the most promising area in medicinal chemistry and, possibly, the next major breakthrough. Recent advances in genomics, proteomics, and related fields are making it possible to tailor treatments to an individual's specific genetic and disease profile. This will be further accelerated by the integration of artificial intelligence into medical development programs, which can help identify personalized treatment options based on large-scale data analysis.
How did you get interested in Medicinal Chemistry?
It was during my bachelors. I remember perfectly the first time I saw a compound co-crystallized with its protein target and how well it was fitting. In that moment, I became fascinated by the fact that we can design and synthesize molecules that perfectly fit into a protein pocket and exert a biological effect.
Where and when did you obtain your PhD diploma?
I obtained my PhD from the University of Barcelona / IRB Barcelona in 2020. After my PhD, I shifted to industry right away.
After my bachelor, I became interested in finding new methodologies to target intrinsically disordered proteins (IDPs). IDPs are a class of proteins that do not have a stable tertiary structure, therefore are not amenable to structure-based drug discovery methods. Because of that, these targets have been historically considered to be “undruggable” even if they represent 30-50% of our proteome and are drivers of many diseases. During my PhD, I designed and synthesized small molecules to modulate the function of the intrinsically disordered region of androgen receptor to treat advanced prostate cancer. Tuning the propensity of the IDP to form biomolecular condensates emerged as a promising strategy.
Where are you currently working and what is your current position?
I am currently a senior scientist at Dewpoint Therapeutics, a biotechnology company advancing the knowledge on biomolecular condensates to identify new targets and mechanisms of action across multiple biological pathways to develop new therapies.
I am interested in the intersection between biology and chemistry, deciphering new mechanisms of action to tackle diseases without a current cure and/or treatment.
How would you explain what your research area is to non-scientists?
The cell is like a factory, where everything needs to work in a regulated manner to deliver a product. However, the cell factory is very crowded and at first glance it seems not very well organized as there are only a few walls and people, departments and machines all share one same open space. So, how can the cell be so efficient in delivering the right products? In 2009, the lab of Anthony Hyman (co-founder of Dewpoint Therapeutics) discovered that cells concentrate activities without the need of building walls by creating a wall-free but separate environment, which we call biomolecular condensates.
Biomolecular condensates bring all the molecules that are needed to perform an activity together in time and space. For example, a biomolecular condensate for packaging can be created on demand, but only when a product is ready to be packaged. At this moment, all the people, machines, and materials would be brought together, and the product would be put into boxes. Once the job is finished, it would disassemble.
Later, in 2015, the Hyman lab also discovered that aberrant condensates are hallmarks of diseases with unmet medical needs. His lab focused on neurodegenerative diseases. Subsequently, the lab of Rick Young (also a co-founder of Dewpoint Therapeutics) showed similar results in cancer. I am now studying aberrant condensates in disease to discover new therapies.
What do you like best about your work?
I love the interdisciplinary nature of drug discovery and the constant learning that goes with it. Moreover, drug discovery is a team sport and I enjoy leading and being part of an international multicultural team.
What kind of skills does your work require?
For the technical side of the job, I would say good hypothesis testing, strong data analysis, no fear to innovate and constantly learning. For the people side of the work, excellent communication, pro-activity/leadership and humbleness.
What do you consider your greatest achievement in your scientific career?
To know that the work I do will hopefully deliver novel drugs into the market and help patients.
Which of your papers are you most proud of and why?
The work that I am most proud of is not part of a paper but a patent. I believe basic research is a must, but I thrive when we can translate our laboratory findings into treatments.
What are the features of a successful PhD student or postdoc?
Resilience and curiosity. I would like to emphasize that a successful PhD or postdoc is not measured by the impact of the papers (at least in industry) but the hard and soft skills one acquires during their PhD.
What advice would you give to someone who wants to know more about your field?
Reach out to anyone who can tell you more about it! I am personally always happy to discuss science and career development - and I am sure that everyone else is, too! So don’t be shy!
What would you like to ask from other medicinal chemists?
I imagine a world in which everyone is given the right opportunities because of their capabilities and not based on their gender or background. Unfortunately, there is still a lot of work left to do to achieve (gender) equality in science and we can only achieve it if we all work together.
What is the most embarrassing thing you have done in the lab while doing experiments?
The most embarrassing experience was one day during my first summer internship in which, after the lab, I took the subway home and no-one wanted to sit next to me, although the subway was very crowded. Once home, I realised that I was smelling very bad, like rotten fish, as I had been working with large amounts of an amine all day.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
Which field of medicinal chemistry do you consider the most promising for the future?
The whole pharma world is now investing heavily in RNA therapeutics. Given the large interest in this field, I expect it to yield positive outcomes in the near future.
How did you get interested in Medicinal Chemistry and Chemical Biology?
I was intrigued by the question which structural features make small molecules bioactive and relevant to biology? We then devised new principles and concepts for bioactive compound design (inspired by natural product structures, i.e. classes of compounds that are biologically relevant by definition), developed the corresponding synthesis programs (including new enantioselective catalysis methods), evaluated the new compounds in unbiased phenotypic assays, identified and validated the targets, and finally explored the most promising compounds in disease-relevant settings. This continuum of investigations defines chemical biology research leading straight into medicinal chemistry.
Where and when did you obtain your PhD diploma?
I graduated from the University of Mainz in 1985. My thesis focussed on the development of new protecting group strategies for glycopeptide synthesis. Working in the group of Horst Kunz, I introduced the allyl ester into glycoconjugate synthesis. Afterwards, I did my Post Doc with George Whitesides at Harvard University in 1985-1986.
Where are you currently working and what is your current position?
I jointly hold positions as Director of the Department of Chemical Biology at the Max-Planck-Institute of Molecular Physiology in Dortmund and as Full Professor of Biochemistry in the Faculty of Chemistry and Chemical Biology at TU Dortmund.
My work requires being a scientist and researcher, teacher, mentor, manager, advisor, consultant, company founder, ….. (as holds for many, if not all of my peer group).
What are your current research interests?
The underlying question described above has been a consistent motivation for my group. We are a team of organic chemists, biochemists, biologists and computer scientists which fuse these disciplines into chemical biology research. We develop new concepts for bioactive compound design (now integrating underlying principles of chemical evolution), synthesize these compounds, including the development of new methods, e.g. in enantioselective catalysis, investigate the resulting compound collections in target-agnostic phenotypic and morphological cellular assays and then identify the cellular targets and modes of actions of the new bioactive compounds, and if these are related to human disease we advance them into drug discovery. This multidisciplinary program has given rise to a “Chemical Evolution of Natural Product Structure”, and “Pseudo-Natural Products” now in preclinical investigation.
What do you like best about your work?
The freedom to work on what interests me most, and the singular moments of discovery and insight.
What kind of skills does your work require?
Most important is the ability to repeatedly generate good ideas, see underlying principles behind data sets and derive new concepts and principles from them which will then guide future research. But people skills and the ability to motivate come next. In science being a good communicator is of high importance. And, finally, a certain degree of robustness, both mental and physical, is required. Personally, for long-time success, I try to consistently operate at 95% of my maximal capacity (which requires that the 100% threshold has been identified), which leaves sufficient bandwidth to go beyond 100% on short notice and whenever required.
How many PhD students and postdocs do you currently supervise? Are you currently looking for a new PhD student or a postdoc?
Currently, we are a group of ca. 25 students, Post Docs, Senior Scientists and associates. Applications by excellent Post Doc candidates are always welcome. Since I will adopt Emeritus status in the coming years, I do not accept Ph. D. students in my group anymore.
How would you describe yourself as a supervisor?
Good science needs the air of freedom to explore own ideas and to be creative, and I leave my students and Post Docs the required room. Certainly, I am demanding, and all members of my group work hard. But I will always welcome a good beer on a Friday afternoon and a barbecue on the terrace adjacent to the lab. The social atmosphere in a group is of high importance.
What are the features of a successful PhD student or postdoc?
Be rich in creative ideas, boldly tackle them, work hard to reach your goals and differentiate the doable from the unreachable. In other words: inspiration, motivation, transpiration.
What would you like to ask from other medicinal chemists?
Don´t be dogmatic (dogma never helps), and don´t be shy to embrace new developments and new fields. After all, the ultimate goal is to cure diseases. The patient does not care whether this is achieved by a small molecule, a peptide, a protein or a nucleic acid vaccine. These are all chemical entities, hence their discovery and development needs medicinal chemists.
Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?
At times reviews (for instance of papers and applications, or by company-internal Boards) are perceived unfair, but I cannot say that I faced such an outcome too often. In my experience, taking such situations easy and not being too annoyed (of course, there is annoyance; nobody wants to be rejected) helps. Take out emotions, sleep over it once, and then react, tomorrow will be a new day. You win a few, you lose a few … let´s continue.
What do you consider your greatest achievement in your scientific career?
I consider the discovery of general concepts to guide organic synthesis for chemical biology and medicinal chemistry, as the work that will have widest and long-lasting impact. We progressed from natural products and Biology-Oriented Synthesis to Pseudo-Natural Products and a chemical evolution of natural product structure.
Which of your papers are you most proud of and why?
The concepts have been developed and proven in a series of papers. They are detailed in three Concept articles in Nature Chemistry (2020), Angewandte Chemie Int. Ed. (2021) and the Journal of the American Chemical Society (2022). The original Biology-Oriented Synthesis idea was developed in three papers in the Proceedings of the National Academy of Sciences in 2004-6, and the Pseudo-Natural Product principle was first described in a Nature Chemistry paper in 2018.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
In the introductory organic chemistry lab course, I managed to explode a small flask I held in my hand. Fortunately, there were no serious consequences. This experience taught me to be cautious, and I never had to face such an accident again.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
For Medicinal Chemists I recommend “The Billion Dollar Molecule” and its congener “The Antidote” (both by Barry Worth). This case-study showcases the rise of the Biotech era in the few square meters around Kendall Square, Cambridge, Ma since the mid-eighties. It is entertaining to read (you will know the main characters), and gives an insight into the early days of the Biotech Industry. Those who know Kendall Square in 1986 and 35 years later may have good stories to tell at dinner.
Which scientist do you admire the most and why?
I am fascinated by Justus von Liebig and Emil Fischer. Liebig is considered the Founder of Organic Chemistry and of Agricultural Chemistry and worked on Physiology as well. Fischer raised Organic Chemistry to unprecedented heights (beautifully showcases for instance in his first total syntheses of carbohydrates), and his research ranged from amino acids and saccharides through heterocycles and peptides to proteins and enzymes. He proposed the “lock and key” principle.
Which field of medicinal chemistry do you consider the most promising for the future?
Among the therapeutic areas I note a rising interest and promise in targeting immunological disorders, and I have shifted much of my own interest there. In terms of targets, modulation of RNAs and of transcription factors hold a lot of promise. We will have to be open to different chemical modalities.
What would you expect to be the next major breakthrough in medicinal chemistry?
We will learn how to systematically identify and develop small molecules that will not inhibit or activate their targets, but that will induce modulation of their activity by different mechanisms and modes of action. Induced target degradation is a first example for this generation of drug discovery programs.
Can you tell us more about your background?
I received my PhD diploma in chemistry (cum laude) from Utrecht University on April 2002. My thesis was about the metabolism and neuroprotective properties of anandamide, an endogenous ligand of the cannabinoid receptors. After a post-doctoral position in cell biology in the lab of Prof. dr. Vincenzo di Marzo, I worked for almost eight years in the Research Laboratories of Merck (former Organon) in the Netherlands. I was a group leader in the medicinal chemistry department of Prof. dr. Stan van Boeckel and served as project leader for several programs ranging from hit identification up to clinical candidate selection. In 2012, I decided to go back to academia to start my own research group, where I combine medicinal chemistry with chemical biology at Leiden University.
Where are you currently working and what is your current position? What are your current research interests?
Currently, I am a full professor and chair of Molecular Physiology at the Leiden Institute of Chemistry and a principal investigator of Oncode Institute. Our aim is to design, synthesize and apply chemical tools to study important biological and biomedical questions. We have a focus on kinase and lipid signalling. We use techniques from different fields, including chemical biology, computational chemistry, medicinal chemistry and molecular biology, to determine and predict the interaction of small molecules with proteins in physiological and disease processes.
Our long-term aim is to discover drug candidates to treat cancer, (drug-resistant) infections and brain disorders. The group consists of two assistant professors (Dr. Stephan Hacker and Dr. Anthe Janssen), 4 post-docs, 16 PhD-students & technicians and >20 M.Sc and B.Sc students. We are embedded in the Leiden Early Drug Discovery network (https://www.universiteitleiden.nl/en/science/led3). Finally, I am the workstream leader of small molecule drug discovery from Oncode-PACT, an (inter)national consortium that has recently been awarded 325 million Euros from the Netherlands government to accelerate preclinical drug discovery for oncology (https://www.oncode.nl/Oncode-PACT).
What do you consider your greatest achievement in your scientific career?
Van Esbroeck et al., Science, 2017, 356, 1084
https://www.science.org/doi/abs/10.1126/science.aaf7497
Ogasawara et al., Proc. Natl. Acad Sci. USA, 2016, 113, 26
https://www.pnas.org/doi/abs/10.1073/pnas.1522364112
Mock et al., Nature Chem. Biol., 2020,16, 667
https://www.nature.com/articles/s41589-020-0528-7
Van der Wel et al., Nature Comm., 2020, 11, 1
https://www.nature.com/articles/s41467-020-17027-5
To have a successful PhD, it is important that you are intrinsically motivated and are curious to learn new topics and techniques. Read the literature, go to conferences and talk to people. You are venturing into new, unknown territory; therefore, it is important to be perseverant, not to give up when something is not working the first, second or even a third time. If it was easy, then somebody else would already have done it.
I like to work on the interface between chemistry and biology, because I am convinced that new chemical tools and methods will allow us to address important biological questions. In my group chemists and biologists work closely together and they have to learn to speak each other’s language to move their projects forward. Thus, team spirit, collaboration and good communication skills are important as well. If you share success, it will become bigger.
What is the most embarrassing thing you have done in the lab while doing experiments?
At the first day of my PhD, I made use of a magnetic stirrer to dissolve some components of a buffer. I put the bottle next to a flask of a colleague. I did not know the magnetic stirrer was also a heating block. By turning it on, I accidently denatured her precious protein preparation, which had taken her several weeks to obtain…. that was quite an introduction. Fortunately, we could still get along after this embarrassing mistake.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
Of course, everyone working in medicinal chemistry should read the blog ‘In the pipeline’ from Derek Lowe.
Which scientist do you admire the most and why?
As a medicinal chemist/chemical biologist, I think it is important to develop technologies that will allow us to predict and characterize the interaction of small molecules across the entire human proteome in a living cell. Computational chemical biology (such as machine learning) combined with chemical proteomics, metabolomics and molecular & structural biology will allow us to make a molecular encyclopaedia of ligand-protein interactions and their function. Single molecule resolution imaging techniques using specific fluorescent probes will allow us to localize where these interactions take place in cells or tissues. Together, this will provide a better molecular understanding of human biology in health and disease and will lead to more efficacious and safer drugs in an efficient manner.
How did you get interested in Medicinal Chemistry?
Through natural product total synthesis; I was always impressed by what Nature’s bounty could achieve in modulating biology and wanted to try my hand at it.
Where and when did you obtain your PhD diploma?
Boston College, 2007
What was the topic of your PhD project
Total synthesis of a marine natural product of no known use
Where did you have your postdoc position?
ETH Zürich, with Prof. Donald Hilvert
Where are you currently working and what is your current position?
Associate Professor of Chemistry, University of Basel
What are your current research interests?
Performing complex chemistry on DNA as well as using small molecules to degrade proteins
How would you explain what your research area is to non-scientists?
Designing precision tools on the molecular scale to change biological processes
What do you like best about your work?
Always new problems to solve, always new stuff to learn
What kind of tasks does your work involve?
Considering problems in biology and designing molecules to study those problems
What kind of skills does your work require?
Synthetic chemistry, cell biology, molecular biology, analytical chemistry
What do you consider your greatest achievement in your scientific career?
I can’t point to one discovery. Looking back over an area of research with many discoveries is what I consider achievement.
Which of your papers are you most proud of and why?
https://pubs.rsc.org/en/content/articlelanding/2015/sc/c5sc00921a
This paper outlines our discovery that suitably placed boronic acids accelerate and improve oxime formations. We studied it as a bioconjugation tool and it continues to be used in many areas.
https://pubs.rsc.org/en/content/articlehtml/2016/sc/c6sc03502g
An unusual and unexpected discovery for us: copper carbenes, which we thought would be extremely reactive, can actually deliver clean synthetically useful modifications of nucleic acids.
https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201902513
We executed a large complex synthesis on DNA, pushing the synthetic limits of on-DNA chemistry.
How many PhD students and postdocs do you currently supervise?
Are you currently looking for a new PhD student or a postdoc?
Currently we are 13 people and could expand to 15.
What are the features of a successful PhD student or postdoc?
Fearlessness: The willingness to step outside of your comfort zone and learn new things.
How would you describe yourself as a supervisor?
Curious, attentive, willing to help.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
Refluxing reaction exploded, stunk out the whole building…leading to an “investigation”.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
Anything by Steven Pinker, Richard Dawkins, Hans Rosling
Which scientist do you admire the most and why?
Steven Pinker – For his ability to change the world with simple logic and accessible argumentation.
Have you experienced any unfair situations during your scientific career?
Absolutely, but many people of different skin colour or gender than me have had it much worse.
Which field of medicinal chemistry do you consider the most promising for the future?
Building molecules that are capable of executing complex functions.
What advice would you give to someone who wants to know more about your field?
Come and work in my lab.
What would you like to ask from other medicinal chemists?
Send your best students to my lab.
What would you expect to be the next major breakthrough in medicinal chemistry?
Small molecules collaborating with biologics in immune-oncology
Where and when did you obtain your PhD diploma?
I obtained my PhD in Biological and Medicinal Chemistry in 2009 from the University of Queensland, Brisbane, Australia.
What was the topic of your PhD project?
Peptide Engineering – Controlling the folding of disulfide-rich peptides. My PhD focussed on developing new methodologies to accelerate the discovery and characterisation of bioactive peptides from animal venoms. Such venom peptides are valuable molecular probes and promising therapeutic leads due to their exquisite potency and selectivity.
Where did you have your postdoc position?
2009-2011: in the laboratory of Prof. Paul Alewood (venom peptide drug discovery) at the Institute for Molecular Bioscience, at the University of Queensland, Brisbane, Australia.
2011-2013: as a Marie Curie Fellow in the laboratory of Prof. Philip Dawson (inventor of native chemical ligation) at the Scripps Research Institute in La Jolla, California.
2013-2015: as a Marie Curie Fellow in the laboratory of Prof. Fernando Albericio (peptide chemistry) at the Institute for Biomedical Research, Barcelona, Spain.
Where are you currently working and what is your current position?
I am an Associate Professor and lead two research laboratories, one at the Institute of Biological Chemistry at the University of Vienna, Austria, and one at the Institute for Molecular Bioscience at the University of Queensland, Australia.
What are your current research interests?
My research interests are centred around neuropeptides and natural product drug discovery with a particular focus on bioactive peptides derived from animal venoms. We take advantage of these vast natural peptide libraries to identify new molecular probes and therapeutic leads for the study and treatment of neuropathic pain, gastrointestinal disorders, breast cancer and autism.
How would you explain what your research area is to non-scientists?
We investigate how diseases work and develop therapeutic strategies to treat them.
What do you like best about your work?
The intriguing links between nature, chemistry, biology and medicine.
What kind of tasks does your work involve?
Going on field trips, collecting venom, discovering and synthesising new bioactive compounds, understanding their interactions with human physiology, and developing drug candidates to improve human health.
What kind of skills does your work require?
Scientifically: a good understanding of chemistry, pharmacology, biology
Equally important: perseverance, curiosity, optimism, and a good team to work with.
What do you consider your greatest achievement in your scientific career?
Still in the making, but it is already great to be finally in a position where I can pursue and translate several of my ideas. The next few years will be highly interesting to see if these new approaches also pan out!
Which of your papers are you most proud of and why?
There are several publications that come to my mind for different reasons, but two are certainly special to me: my first JACS paper: Solving the α-conotoxin folding problem: efficient selenium-directed on-resin generation of more potent and stable nicotinic acetylcholine receptor antagonists –– as it describes key aspects of my PhD work and provided me with confidence that I can produce innovative and high quality of work; and our latest Nature Reviews Drug Discovery Review, Trends in Peptide Drug Discovery – as it provides an in-depth overview of the field I work in covering the peptide drug discovery and development landscape from its beginning to its future.
How many PhD students and postdocs do you currently supervise? Are you currently looking for a new PhD student or a postdoc?
11 postdocs and 6 PhD students. Yes, I am always looking for talented people with the right background and passion.
What are the features of a successful PhD student or postdoc?
I would be lying if hard-working wouldn’t be part of the top three. Cutting-edge research is highly challenging and a strong science education with well-developed laboratory skills is necessary to start tackling significant challenges. A positive can-do-attitude coupled to independent and innovative thinking is also very important.
How would you describe yourself as a supervisor?
Supportive, facilitating, with high expectations. I like to see people succeed.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
Yes, I did blow up a fume hood …. luckily no-one got hurt.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
Book: Perfume, by Patrick Süskind
Movie: Memento
Blog: In the pipeline https://blogs.sciencemag.org/pipeline/
Which scientist do you admire the most and why?
Stephen Kent – highly innovative and advanced our field in many new directions.
Have you experienced any unfair situations during your scientific career?
I am sure I have – the trick is to forget them fast and not let them get to you – there are always bigger and more important things to focus on.
Which field of medicinal chemistry do you consider the most promising for the future?
Peptides of course ;) I don’t think there is one specific field that stands out, it's the diversity and complementary nature of many approaches and technologies that counts.
What advice would you give to someone who wants to know more about your field?
A good place to start would be our review: Trends in peptide drug discovery. Nature Reviews Drug Discovery; take some online Medicinal Chemistry or Chemical Biology lectures.
What would you like to ask from other medicinal chemists?
Keep up the good work!
What would you expect to be the next major breakthrough in medicinal chemistry?
That’s a tough one – I think more advanced drug delivery technologies will play an important role as this remains a limiting step for many otherwise promising therapeutic approaches.
How did you get interested in Medicinal Chemistry?
I always loved chemistry; my mum is an analytical chemist and I always loved to visit her at work. I had hard time deciding whether to study Chemistry or Pharmacy. I ultimately decided to study Pharmacy since I not only wanted to learn how the molecules are made but also understand what they do with the human body. Medicinal Chemistry allows me to combine these two aspects: great organic chemistry and pharmacology.
Where and when did you obtain your PhD diploma?
In 2013 at the University of Münster, in the group of Prof. Dr. B. Wünsch.
What was the topic of your PhD project?
Synthesis of Novel Chemokine Receptor 5 Antagonists by Late-Stage Diversification and Evaluation of their Structure Affinity Relationships. It was the perfect topic for me, combining novel chemistry (C-H activation) with interesting pharmacology. The work was also highly interdisciplinary, which I particularly enjoyed.
Where did you have your postdoc position?
My first postdoctoral position was in the group of Prof. Dr. C. E. Müller, Bonn University, working on a project within the Neuroalliance Consortium´. It was a collaboration project with UCB pharma, which provided me with the opportunity to get insight into the industrial site of research.
My second postdoc position was in the group of Prof. Dr. K. A. Jacobson at the NIH, Bethesda. Here I worked on several projects: adenosine receptor ligands, P2Y14 receptor antagonists and had the opportunity to start the project on CD73 inhibitors in collaboration with C. E. Müller.
Where are you currently working and what is your current position?
My own research group, funded by the Emmy-Noether program of the German research foundation, is located at the European Institute for Molecular Imaging (EIMI) at the University of Münster. We design, synthesize, and pharmacologically characterize novel receptor ligands for diagnostic and therapeutic applications in the fields of cancer, inflammation, and neuropathic pain.
How would you explain what your research area is to non-scientists?
We create molecules to answer diagnostic questions and help to develop new therapies.
What do you like best about your work?
It is never dull or boring. Every day you learn something new, get a new piece of the puzzle.
What kind of skills does your work require?
My work consists of teaching and research. For teaching, you need good communication and presentation skills. For research, besides enthusiasm and perseverance, you require a lot of management skills: you have to be in the moment and think ahead at the same time.
What do you consider your greatest achievement in your scientific career?
Well, I more or less recently started my independent career; therefore, I hope my greatest achievement is still to come.
Which of your papers are you most proud of and why?
The one I am currently preparing on the imaging of CD73 expression in cancer.
How many PhD students and postdocs do you currently supervise?
6 PhDs, 2 Master students, no postdocs at the moment
What are the features of a successful PhD student or postdoc?
I always tell my PhD students 6 months in their project, they should be able to tell me something about their target that I do not know. Knowing the literature and good planning is in my opinion as important as enthusiasm and perseverance in research.
How would you describe yourself as a supervisor?
I try to create a productive environment and enough space for every group member to pursue their research projects and develop themselves. I think it is important to treat every person with equal respect and decency regardless of their position or status from intern to professor. This is the mantra I live by as a private person and as a supervisor. I don’t take myself too seriously.
When I get an idea, I go straight to the lab to discuss it. One of my PhD students just recently told me:’What’s up? You have that look on your face again.’ We laughed, discussed, and a new subproject was born. I think this pretty much describes me as a supervisor.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
Well, during my time at the NIH, I quenched what I thought was a little bit of NaH on the balance with isopropanol (standard procedure of traces of NaH), overlooking that a bigger piece of NaH got under the balance. The moment it got in contact with some isopropanol, it caught fire. Besides burning down the balance and the mess caused by the fire distinguisher, nothing bad happened. I was embarrassed and devasted. Ken Jacobson laughed it off and told me ‘I wish this will be the worst and the only bad thing happening to you throughout your career.’ So far, his wish came true.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
I like the novel Cantor’s dilemma by Carl Djerassi, Dr. GPCR podcast. I cannot think of a recommendation for a film for science, but don’t get me started on recommendations for movies in general unless you want to hear everything about Quentin Tarantino’s work.
Which scientist do you admire the most and why?
There are many scientists I admire and look up to, but Ernest Rutherford would be the one I admire the most, not only for his immense contributions in Physics and Chemistry but also for his inspirational leadership (eleven of his students received a Nobel prize) and for his modesty.
Have you experienced any unfair situations during your scientific career?
Fairness is a complex matter. I do not consider myself experiencing unfair situations with a significant impact on my career so far. In my opinion, sometimes situations can be quickly diffused by addressing the issue upfront.
Which field of medicinal chemistry do you consider the most promising for the future?
Incorporation of AI in drug development.
What would you expect to be the next major breakthrough in medicinal chemistry?
The development of checkpoint inhibitors for cancer therapy, it has already provided some great results, but I am certain there is more to come.
How did you get interested in Medicinal Chemistry?
I came first into contact with molecules that interfere with a biological system during a Biology lesson at school. Then we were tasked to write an assay-like text about antibiotics. A glimpse into lexica showed fascinating molecules and fascinating modes of action. This fascination never died, but shifted over the years to the question how to find such molecules in the first place.
Where and when did you obtain your PhD diploma?
I obtained my PhD in the group of Prof. Christa Müller (University of Bonn) in 2007. The topic of my PhD project was the design and synthesis of nucleotide mimetics as ectonucleotidase inhibitors.
Where did you have your postdoc position?
In the groups of Prof. Christa Müller (University of Bonn) and Prof. Jonathan Hall (ETH Zürich)
Where are you currently working and what is your current position?
I am currently a research group leader at TU Dortmund University.
What are your current research interests?
My group is working on the technology of DNA-encoded screening libraries. Basically, we are wondering how to populate the chemical space of these libraries. Is there something like an ideal screening library? In the light of the theoretically synthesizable chemical space, design of screening libraries is a daunting and intellectually stimulating task. Yet, finding novel biologically active chemical matter on a challenging target is so highly rewarding.
What do you like best about your work?
The freedom to pick a scientific problem and the freedom to walk new ways to work on this problem. A fantastic aspect of a small molecule screening platform technology is that you can venture into many (though certainly not all!) biological targets.
What do you consider your greatest achievement in your scientific career?
There is not the one greatest achievement, but rather a gradual learning process how to combine best the different scientific disciplines required for library design, screening, and then the follow-up once a molecule has been identified.
Which of your papers are you most proud of and why?
Difficult to answer, but I would say they fall into the category of “first-time disclosures”, and they raise a lot of questions that need to be answered in further studies. I would pick the identification of a microRNA-lnc-RNA interaction by a chemical biology strategy (Nat Chem Biol, 2015), the demonstration that a certain DNA design enables a broad chemistry scope on oligonucleotide conjugated starting materials (Chem Sci, 2017), the observation that micelle-promoted catalysts enable on-DNA reactions (J Am Chem Soc, 2019), and the identification of TEAD-YAP inhibitors from a small, designed DEL (ACIE, 2020).
What are the features of a successful PhD student or postdoc?
Curiosity and passion, and a lot of discipline and affinity for the written word.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
Nothing to report here. I am sorry. DNA and RNA do not explode, they die a silent death.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
I enjoy reading the blog “In the pipeline” by Derek Lowe. A must-read is the book “In search of the magic bullet”.
Which scientist do you admire the most and why?
I would rather say that I am fascinated by the early era of drug research. How was it possible at all to venture into trying to cure disease with so little knowledge about physiology and toxicology, and they did not even have an NMR machine to fully and timely understand what they were making. Did nobody tell these researchers that drug research is impossible under these circumstances?
Which field of medicinal chemistry do you consider the most promising for the future?
I do not know whether it is the “most” promising field, but in my opinion the modulation of intracellular protein-protein interactions holds much promise, and with technologies that enable handling unprecedented chemical space - be it virtual or real - I hope we will witness more breakthrough stories in this field.
What would you like to ask from other medicinal chemists?
Don´t underestimate the impact of technologies but readily embrace them, and the value of innovative chemistry for compound design.
How did you get interested in Medicinal Chemistry?
I got interested in chemistry quite early, around the age of ten. At that time, however, I was more fascinated by let's say the reactions of compounds in high oxidation states. Later, towards the end of secondary school, I became more and more interested in the interactions of chemical compounds with biological systems, which was also partly due to my very passionate chemistry teacher who always established a link between chemistry and biology. When I started studying chemistry, it was already clear that I wanted to specialize in Medicinal Chemistry or Chemical Biology later on.
Where and when did you obtain your PhD diploma?
After studying chemistry in Karlsruhe, Heidelberg, and Montpellier, I went to Tübingen University to join the group of Prof. Stefan Laufer where I obtained my PhD in 2014. My main project aimed at the synthesis of non-covalent and covalent inhibitors of Janus kinase 3 (JAK3).
Where did you have your postdoc position?
I did my postdoc in the group of Prof. Karl-Heinz Altmann at ETH Zürich. I had a great time working on the total synthesis and investigation of the molecular mode of action of mycolactones, a class of natural products known as the virulence factors of Mycobacterium ulcerans causing the neglected disease Buruli ulcer.
What are your current research interests?
Most of my research centers on targeted covalent inhibitors for protein kinases as well as the chemistry enabling covalent targeting approaches. Besides, my group is also working on some other target classes including HECT-type E3 ligases. Currently, my major focus is on the development of chemical probes for understudied targets, but I'm also aiming for more translational research projects.
What do you like best about your work?
The diversity of challenges, the freedom to choose my own research fields, and the possibility to discover new things every day.
What kind of tasks does your work involve?
Research, teaching, leading a team, acquisition of funding and (unfortunately too many) administrative tasks.
What kind of skills does your work require?
Many! Curiosity is probably the most essential one but knowledge, creativity, critical thinking, commitment, persistence, social-, communication-, and team leader skills as well as intuition are also quite important.
What do you consider your greatest achievement in your scientific career?
I think that one is still about to come. :)
Which of your papers are you most proud of and why?
I've been involved in many interesting projects resulting in publications on covalent inhibitors for kinases like JAK3 and BMX, but also on the elucidation of the molecular mechanism of the neglected disease Buruli ulcer. Still, the paper I'm most proud of is my Perspective article on covalent "warheads" published 2019 in J. Med. Chem. It took me a lot of effort to write this paper but once it was published, it really received much attention in the community and I got very positive feedback. At the end, it was absolutely worth the investment!
How many PhD students and postdocs do you currently supervise? Are you currently looking for a new PhD student or a postdoc?
I'm currently supervising four PhD students and one postdoc. I'm always happy to receive interesting applications, but I cannot offer any funded positions at the moment.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
In the first months of my PhD thesis, I made a few beginner's mistakes. For example, I was a bit overambitious in scaling up a heterocycle chlorination reaction to generate larger amounts of my core scaffold. Unfortunately, a 2L beaker full of ice wasn't enough for quenching 300 mL of phosphoryl chloride and it came to a runaway reaction. Cleaning the fume hood was awful! Around the same time, I also had a little accident spilling a portion from a large scale Parikh-Doering Swern oxidation. You can imagine that my popularity in the lab wasn't very high on that day!
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
I can recommend the #MedChemCASES webinars organized by the GDCh Medicinal Chemistry Division's NextGenMedChem group (which I'm glad to be part of)!
Which field of medicinal chemistry do you consider the most promising for the future?
I would not dare to select a single one. We are currently seeing a rise of new enabling technologies such as cryo-EM, DNA-encoded libraries, AI-driven drug discovery and protein structure prediction and substantial advances in chemoproteomic profiling techniques, which I expect to trigger significant transformations in the field. Moreover, novel modalities like molecular glues or PROTACs open up new targeting paradigms and expand the scope of what we consider druggable. At the same time, I think a lot of discoveries remain to be made in traditional target families. If you consider, for example, that so far roughly a third of the human kinome is severely understudied and the same applies to many other target classes, this suggests that a lot of "hidden treasures" are still waiting to be discovered.
What would you expect to be the next major breakthrough in medicinal chemistry?
If I could predict that, I would be rich! I think medicinal chemists will keep pushing the boundaries in many different areas and emerging technologies like cryo-EM, CRISPR-Cas or AI will facilitate this process. One thing I'm definitely very excited about is the outcome of the ongoing clinical trials with the first PROTAC degraders.
Our first interviewee for 2021 is the winner of the EFMC-YMCS 2020 presentation prize, Ms Jessica Reynolds from the University of Oxford, United Kingdom. She is currently writing her DPhil thesis and has been awarded the EPSRC Doctoral Prize, allowing her a further six months after hand in to complete her work with Professor Stuart Conway, and explore new ideas.
What is the topic of your PhD project?
My project focuses on exploring different chemical tools to probe the function of TRIM proteins. We have developed small molecule probes targeting the bromodomain of TRIM33, and have incorporated these ligands into the design of proteolysis-targeting chimeras.
What do you like most in your job?
I enjoy the collaborative and interdisciplinary nature of medicinal chemistry, which provides so many opportunities for learning new skills. Sharing knowledge and expertise is certainly the best way to advance science!
Which scientist do you admire the most and why?
I really admire Frances Arnold for her work on directed evolution of enzymes, the applications of the work are astounding and will definitely change our world for the better.
Which field of medicinal chemistry/chembical biology do you consider the most promising in the future?
I think PROTACs are fascinating tools for probing protein function. I am very interested to see the results of the cancer-targeting PROTACs currently in clinical trials. If they are successful, it will open up a whole new path for cancer treatment.
How did you get interested in Medicinal Chemistry?
During my PhD and Postdoc training I have worked at the interface between biology and chemistry and during that time I have become intrigued to pursue my scientific career at this interdisciplinary interface. In addition, I felt it is highly motivating and rewarding to work towards solutions to improve human health.
Where and when did you obtain your PhD diploma?
My PhD thesis I have carried out in the membrane biochemistry unit under the supervision of Dieter Oesterhelt at the Max-Planck-Institute for Biochemistry in Martinsried near Munich in Germany. I have joined Dieter Oesterhelt’s lab in 1987 after I had completed my Master thesis with Dieter Seebach at ETH. My wish at the time was to complement my training in organic chemistry at ETH with a biology/biochemistry focused thesis.
What was the topic of your PhD project?
During my thesis I have investigated the role of the protein environment to facilitate electron transfer in the photosynthetic reaction center of bacteria. The focus of my thesis was to create protein mutants of the reaction center and thereafter to study mutated proteins by a number of biophysical methods including femtosecond spectroscopy and x-ray analysis. The work was stimulated by the groundbreaking work in Martinsried in the mid-late 80ies leading to the first crystal structure determination of a membrane protein.
Where did you have your postdoc position?
For my Postdoc studies I have joined the laboratory of Peter Dervan at the California Institute of Technology in Pasadena. My work was focused on establishing a new modality to selectively target DNA.
Where do you work at the moment and what is your current position?
At present I’m leading a cross-functional R&D unit for Novo Nordisk out of Boston. My scientific focus is to ideate and advance new therapeutic concepts/modalities to treat cardiometabolic and rare diseases.
What do you like most in your job?
My job involves both scientific and business development tasks. We are looking into new emerging science in academia and at Biotech companies to identify new opportunities to develop jointly novel therapeutic concepts. Once we have come across promising new scientific opportunities we envision and negotiate suitable partnership frameworks to collaborate with our partners. We thereby focus on partnerships where both the partner and us contribute with scientific knowledge and capabilities.
Every day I enjoy learning about new and exciting science and at the same time to have the opportunity to interact and work together with many wonderful colleagues around the globe.
What kind of skills your job requires?
It is a science focused job which requires a broad scientific insight into biomedical research and drug development. In addition, my role requires business insight, business development skills, and the ability to build teams and collaborate across organizations and diverse backgrounds.
What do you consider your biggest achievement in your scientific career?
Over a long career in industry I had the opportunity to contribute to more than 50 drug candidates which have progressed into various stages of clinical development. It has been a stimulating and rewarding experience to work together and mentor many talented scientists during this journey.
What is the most embarrassing thing you did in the lab while doing experiments?
As students we were running a distillation and inexperienced as we were we did not take the needed precaution to capture non condensing solvent vapor. The solvent vapor was crawling back on the bench and ignated at the heating plate. A flame went up to the ceiling and a heat wave went through the laboratory which could be felt several meters away. Luckily no one was severely injured as the amount of solvent involved was very small. This accident left a lasting impression on me and was teaching me to take great care to anticipate potential adverse events in the laboratory to prevent accidents from happening.
Which scientist do you admire the most and why?
Over the course of my carrier I have met many remarkable scientists and colleagues. Naturally, my academic supervisors and mentors Dieter Seebach, Dieter Oesterhelt, and Peter Dervan had a great influence on me as a young scientist.
Did you experience any unfair situations during your scientific career?
There will always be biases in personal judgements. At the same time my experience is that in sound and healthy organizations checks and balances including escalation mechanisms are in place to mitigate those biases. There is no time to waste leaving an organization where this is not the case.
Which paper of yours you are the proudest of and why?
My very first paper was published during my Master thesis at ETH. We had studied the effect of hyperconjugation on directing nucleophilic attacks at carbonyl groups by synthesis of model compounds and subsequent crystal structure analysis. The paper was accepted in JACS (Journal of the American Chemical Society) and it was a rewarding experience to be part of the scientific debate around the role of stereoelectronic effects to direct stereoselective reactions at such an early stage of my career.
Which field of medicinal chemistry do you consider the most promising in the future?
We will see progress on many frontiers. One of the areas I’m excited about are our efforts as a community to innovate new drug discovery modalities with superior target and tissue selectivity over what we have been able to achieve with small molecules so far. This is a field where we are just at the beginning and I foresee that interdisciplinary initiatives will drive future progress.
What would you like to ask from other medicinal chemists?
As scientists I believe we will have to play a very active role to communicate and explain scientific progress and context to society. Each one of us can play a role in this need to communicate scientific advances in an objective, balanced, and understandable way more widely.
What would you guess to be the next major breakthrough in medicinal chemistry?
Medicinal chemistry will continue to make progress on many frontiers. Nevertheless, I would point at two areas where a breakthrough might have a transformative impact:
Our ability to selectively target tissues improving the risk/benefit of new therapeutics
Novel molecular approaches to interfere selectively with the transcription machinery to capitalize on emerging insights on how gene transcription is orchestrated within cells.
How did you get interested in Medicinal Chemistry?
The research areas that I was involved in for my master and PhD theses work and postdoctoral training were not Medicinal Chemistry. However, I was fortunate to be trained in two fields, organic chemistry and mechanistic enzymology, by some of the greatest pioneers and erudite scientists in these fields. So when I began my own lab and launched a program to develop technologies that would allow researchers to decode the biological behavior of natural reactive electrophiles with precision, I became more and more aware of how these accumulating data in this field and our own insights directly impinge on covalent drug design. So we started thinking about understanding the precise mode-of-action of emerging electrophilic pharmacophores. This avenue ultimately drew me further into medicinal chemistry and I became very excited about how our work can directly contribute to this field.
What was the topic of your PhD project?
I did my PhD with Professor David A. Evans at Harvard University, USA - The topic was In the area of asymmetric catalysis & new reaction discovery: more specifically, ‘development and applications of organosilanes as stable, environmentally-benign & versatile cabanion equivalents’.
Where do you work at the moment and what is your current position?
At EPFL, I am an associate professor and the director of the laboratory of electrophiles and genome operation (LEAGO) https://leago.epfl.ch
What are your current research interests?
They have always been rather broad and deeply interdisciplinary. For the most recent years/near future, we are keenly pursuing new knowledge regarding reactive electrophile/covalent-ligand signaling at individual protein-and-ligand-pair-specific and context-specific manner. In parallel, we are also actively researching unexpected moonlighting functions of disease-relevant proteins. In both directions, we strive to see comprehensive mechanistic understanding both in vitro and in relevant living models.
What do you like most in your job?
The simultaneous opportunity to be an educator and an innovator: in terms of the former, the chance to inspire and educate some of the young minds; for the latter, ability to bring something crosscutting to the table that has potential to improve human life and medicine
What kind of skills your job requires?
In science: thinking, critical evaluation (usually questioning conventional wisdom), innovating non-conventional solutions, seeing the big-picture, finding impactful/relevant problems to work on and designing most-insightful experiments, and last but not least, having a strong work ethic. In team-leading and all other services, good mentors/educators manifest excellent communication skills, team-playing, empathy, selflessness, and giving opportunities for the trainees/mentees to thrive in challenging environments, helping mentees prepare for the good times and the tribulations of the next-step of their careers
What do you consider your biggest achievement in your scientific career?
Over the 8-year-span of our lab thus far, it would most likely be the opportunity to have offered to the field the previously-inaccessible ability to quantitatively track the ramifications of non-enzyme-assisted covalent protein modifications by reactive electrophiles. This is the idea behind our T-REX technology, and the underlying concept was not thought of before. With T-REX and related techniques, we began to accumulate paradigm-shifting insights into how electrophile-/covalent-ligand-guided signaling functions at low-occupancy and how these individual ligand-guided events control decision-making
What is the most embarrassing thing you did in the lab while doing experiments?
During my graduate school, shaking a litre-scale separatory-funnel while working up a Shapiro reaction (that was needed for me to prepare a particular vinyl-silane substrate precursor), resulting in N2(g)-driven explosion. Clearly, I wasn’t engaging my brain thereSeveral living and deceased, but perhaps the late Dorothy Hodgkin because I was an undergraduate chemist at Oxford University, Somerville College, where Hodgkin once studied as well as tutored chemists. I thus felt I was directly inspired by Dorothy Hodgkin’s scientific legacy. Furthermore, as a student having not had access to proper education before my arrival to the UK at 17, her legacy made a long-lasting impact on my future career goals since my high-school days in the UK.
Did you experience any unfair situations during your scientific career?
It is surprising to me how many of the common unfair situations we find ourselves in are a projection of our own, or someone else’s interpretation of, our own expectations, situation, or status. It is also surprising how the same gripes are pretty common across different scientific career stages/geolocations/situations. So, the answer is, of course, yes, there are many unfair situations out there; and I still frequently encounter situations I consider to be unfair, both to me, and to others. It is just that the ways these manifest, and to some extent what I choose to tolerate that have changed. But regardless of your situation, I think it is important to keep your chin up and find effective ways to overcome/preempt such situations, especially if you’re in a leadership/group-leader role as this is important for students/trainees. At the end of the day, intelligence along with facts should always (though sadly they do not always) win over.
Which field of medicinal chemistry do you consider the most promising in the future?
Medicinal chemistry is one of the few industries where billions, or even trillions, of dollars are exchanged every year trying to turn something off. We’ve spent years turning enzymes off. Now we’re trying to do the same with scaffolding proteins, oncogenes, shallow binding pockets, and so on. We really need to start to look to mining the resources of the proteome actively (i.e., turning something ON), learning how to harness large gains at small loading, for instance. Such power would be revolutionary.
What would you like to ask from other medicinal chemists?
In one phrase, the answer would be ‘improve real-world relevance’. I think that in this field, one can often get carried away with a lot of in-tube studies or using less relevant models, optimizing Kd with not much else, etc. Once some initial hits/lead data have been obtained, it is quite important to move onto more relevant models/start to answer most relevant questions. As a field, we can do better by not being too bogged down with monodimensional readouts, and by being more broad-minded, having a forward-looking outlook, and taking a multi-disciplinary approach. Prior to initiating a project/model system or an assay, it is first useful to ask to what extent what we are designing/pursuing is of relevance to real-world scenarios. We are better off not pursuing a project/set-up/assay, only because of convenience and of it being within our comfort zone.What would you guess to be the next major breakthrough in medicinal chemistry?
It would be how we understand and manipulate/alter signaling and pathway intersections, and ultimately cell fate/decision making, through gain-of-function activities, i.e., when a ligand binds a target only at low-occupancy. Many drugs and mechanisms-of-action are proven quite effective at substoichiometric target engagement. A similar low-occupancy idea also bodes well for targeting essential genes where complete inhibition is disastrous. However, neither from systems-level or mechanistically, have we even scratched the surface of selectively profiling such proteins (and ligand frameworks) that can be responsive to such gain-of-function druggability.
How did you get interested in Medicinal Chemistry?
As an undergraduate I enjoyed the language and logic of organic chemistry and was motivated to use these skills in an applied setting. I began to explore biomedical sciences and saw Chemical Biology as an opportunity to use chemistry to study life at a molecular level, whilst helping to discover transformational medicines for patients.
Where and when did you obtain your PhD diploma?
At the University of Oxford under the supervision of Prof. Christopher Schofield.
What was the topic of your PhD project?
Chemical biology approaches to study the pathways that cells use to sense oxygen.
Where did you have your postdoc position?
At the end of my PhD, many opportunities appealed to me. I loved the environment of academia but had also become increasingly interested in the translation of research. An opportunity at GSK was advertised and at the interview I was impressed by the freedom to work creatively, and to use innovation to have an impact on the lives of millions of patients. GSK has proved a fantastic place to work, with many outstanding scientists and a culture that follows the science.
Where do you work at the moment and what is your current position?
I am a team leader in a newly formed Chemical Biology department at GSK. My focus is on the development and industrialisation of new technologies to accelerate the discovery of potential new medicines. A big part of my role is to develop collaborations with academia which helps us harness a broader range of ideas to solve difficult scientific problems. I recently joined the Crick-GSK LinkLabs which is a chance to work with world-leading experts in biomedical sciences.
What are your current research interests?
Currently, we are building platforms to rapidly develop inhibitors for targets emerging from genomic studies - an area we are investing in significantly to identify and validate targets. We are also combining chemoproteomic and chemogenomic approaches to discover new targets with therapeutic potential. One focus area is using covalent fragments. Advances in proteomic technologies have created an opportunity to perform covalent fragment screening directly in live cells, providing more comprehensive and biologically relevant information of ligand interactions, while also circumventing the requirement for protein production and assay development. Such approaches enable exploration of unchartered biological space, and generation of large databases of ligand interactions across the proteome.
What do you consider your biggest achievement in your scientific career?
Machine learning and artificial intelligence are two of the most exciting technologies impacting drug development. One of the highlights of my career has been exploring the application of machine learning algorithms to accelerate drug discovery. Right now, I am excited to be at the forefront of the data-rich technologies we are building in chemical biology and to see how these new technologies will impact this field in the next year or so.
How many PhD and postdoc students do you have at the moment?
Are you currently looking for a new PhD and postdoc students?
I work with a team of PhDs at GSK and a team of post docs in the LinkLabs at the Francis Crick Institute. We are always looking for outstanding scientists, look up the GSK-Strathclyde collaborative PhD programme and the GSK-Crick LinkLabs on the GSK website.
What are the features of a successful PhD student or postdoc?
Understanding the context of your work and how it fits in with the research environment around you is essential to help prioritise workflows and focus your efforts for maximum impact. Also, working collaboratively and sharing your science and ideas is hugely beneficial, as well as more enjoyable.
Which scientist do you admire the most and why?
Carolyn Bertozi is doing some fantastic work in chemical biology and glycobiology. If you get the chance to catch one of her lectures or podcasts, I’d recommend it, she presents her work in a remarkably accessible and inspiring way.
Which field of medicinal chemistry do you consider the most promising in the future?
Tough question. I anticipate a shift away from studying one compound at a time in biochemical assays. There are so many exciting technologies and approaches emerging: chemoproteomics, chemogenomics, DNA encoded libraries, machine learning, covalent fragments, PROTACs and other bifunctional molecules. With all of these though, it will be important not to assume the technology will offer all the solutions, but to ensure it amplifies traditional medicinal chemistry.
This week, our #Iamamedicinalchemist is the winner of the Presentation Prize at the EFMC Young Medicinal Chemist Symposium 2019.
Today, our #Iamamedicinalchemist is the winner of the 2019 EFMC Prize for a Young Medicinal Chemist in Academia.
How did you get interested in Medicinal Chemistry?
After studying biochemistry, it was actually our current DPhG president, Prof. Dr. Laufer, and my later supervisor, Prof. Dr. Werz, who rose my interest in this fascinating field.
Where and when did you obtain your PhD diploma?
2009 in Tübingen under supervision of Prof. Dr. Oliver Werz
Where did you have your postdoc position?
In the lab of Takao Shimizu at the University of Tokyo.
Where do you work at the moment and what is your current position?
I am currently group leader and head of the lipidomics facility at the Chair of Pharm./Med. Chemistry in Jena but I will move on October to the Michael Popp Research Institute at the University of Innsbruck, where I was offered a position as professor.
What are your current research interests?
By studying lipid signaling pathways using chemical probes, we aim to identify new drug targets, phytopharmaceuticals and bioinspired lead structures at the interface of cancer, inflammation and homeostasis.
What do you like most in your job?
To confirm revolutionizing hypotheses in collaborative efforts.
What kind of skills your job requires?
First of all, enthusiasm combined with patience and endurance.
How many PhD and postdoc students do you have at the moment?
Are you currently looking for a new PhD and postdoc students?
My team of four PhD students will expand in the near future, and we are currently looking for highly motivated PhD and postdoctoral students.
Which field of medicinal chemistry do you consider the most promising in the future?
I do not think that a single field will stand out but believe that interdisciplinary interactions within medicinal chemistry, chemical biology and beyond will be the key.
What would you guess to be the next major breakthrough in medicinal chemistry?
The dawn of OMICS screening platforms.
Today, our #Iamamedicinalchemist is the winner of the 2019 EFMC Prize for a Young Medicinal Chemist in Industry.
Discover her full-story below!
How did you get interested in Medicinal Chemistry?
Medicinal chemistry is the start of an incredibly long and complex story about getting a drug to the patient. I find being involved at the ‘birth’ of the project and being able to influence and impact how this molecule is made from such an early stage, whilst always keeping an eye on maintaining flexibility and optionality for future production scale, to be fascinating role.
Where and when did you obtain your PhD diploma?
In 2007 – it was a joint program between Vienna University of Technology and University of Chemistry and Technology in Prague.
What was the topic of your PhD project?
Asymmetric Baeyer-Villiger Oxidations using 2nd Generation Biocatalysts.
Where did you have your postdoc position?
1st York Structural Biology Laboratory, University of York, UK as Erwin-Schrödinger Fellow
2nd Dept. of Biotechnology and Enzyme Catalysis, Greifswald University, Germany
Where do you work at the moment and what is your current position?
Novartis Institute for Biomedicinal Research, as a group leader focused on driving progress and adoption of biocatalysis across the entire portfolio and at all stages in a compounds evolution.
What are your current research interests?
Biocatalysis is a subject that I believe has huge value for the synthesis of complex molecules, complementing traditional organic chemistry and providing a way for the pharma (and broader chemical industry) to change their image to one of an industry focused on sustainability and positive environmental impact. My research interests revolve around finding game changing biocatalysis solutions for the production of API’s, which we achieve through application of existing technologies and a constant drive to expand and develop the science though techniques such as protein engineering and bio-conjugations.
What do you like most in your job?
I find the scientific creativity and constant innovation to be very satisfying. Looking at a route and working with synthetic teams to reimagine what’s possible creates an energy and motivation to succeed that is addictive! There is a strong angle on people development in my role that occurs when people engage with biocatalysis and want to learn more and participate in what is naturally a very multi-disiplinary science, operating across a very wide research area.
What kind of tasks your job includes?
Discovery and implementation of novel and established biocatalysis technologies into drug discovery/development, which of course results in the ultimate goal of offering access to late-stage functionalisation capabilities, and the ability to support the drug development process in many tangential ways, such as the synthesis of metabolites. As a group leader, I have line management and various leadership roles, which broaden my role into many other aspects of the Novartis business, into areas as diverse as leading the promotion team, evaluating ‘strategic joint ventures with academic/industrial counterparts and leading a team of people to develop transformational science.
What kind of skills your job requires?
You need to love what you do – as in any field of science the progress is rapid and so staying on top of that becomes a lifestyle rather than a ‘job’! Following the literature, building networks and relationships and constantly looking for opportunities to apply the science is key. Equally being realistic and knowing the limitations of what is possible is key to maintaining credibility :)
Additionally, my job involves dealing with people from many disciplines and backgrounds at various levels in their career, so empathy, an open mind and good listening and communication skills are all vital (maybe a good dose of patience as well)!
What do you consider your biggest achievement in your scientific career?
Outside of being selected for this prize, which I view as an amazing honour, last year our team created a proposal for, and won a “Genesis Labs” award. This is a global competition for independent scientific pursuit, sponsored by Novartis, with the goal of delivering transformational science. We are currently half way through the project, in a very exciting phase.
How many PhD and postdoc students do you have at the moment?
Within my group are many highly experienced researchers who have attained academic excellence at different levels from apprentice to multiple post-docs, and who continue to grow their knowledge and capabilities on a daily basis, solving problems which directly impact the value of the Novartis portfolio. Outside of Novartis I lead a number of academic collaborations, including cooperations with PhD and postdoc students, as well as undergraduate lab courses in the local university.
What are the features of a successful PhD student or postdoc?
What separates a good from a great student is someone who has developed the confidence in their abilities to conduct independent research but maintains a critical internal ‘review process’ so they know when to keep pushing through a challenge or realise a topic is no longer worth pursuing. Being enthusiastic, a good communicator, resilient and supportive of others are all features that make a researcher, at any level, successful in their field. People who understand the impact and purpose of their research always seem to find the ability to ‘keep pushing through’ much better than those who are less involved in the bigger picture of what they are contributing towards.
How would you describe yourself as a supervisor?
I would like to think my team finds me to be the person they can come to when they have a problem, a success or a question. I prioritise finding time to listen to my team, understand their objective/motivation and finding ways to support them as they develop personally and professionally. Seeing people achieve what they thought was impossible, deliver excellence and enjoying their job is what makes me the happiest.
What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?
I think as a researcher, we all have a little bit of a ‘cowboy’ in us and sometimes the drive to get things done quickly overcomes our more rational selves.. leading most people to have had a least a little drama in the lab – I created a little excitement one morning when washing out unreacted sodium from a Birch reactions into the sink...
I also seem to be on a bit of a roll currently with embarrassing acts outside the lab involving pouring coffee over myself, or my boss, or his boss... I don’t think I’m clumsy, but sometimes I gesticulate a little too much with my hands...
Which scientist do you admire the most and why?
Prof. Uwe Bornscheuer! My postdoc boss, he is a wonderful and kind person, 1st class scientist and has a great sense of humor!
Did you experience any unfair situations during your scientific career?
On being awarded a postdoc fellowship, I was told by several of my peers that I had won it only because I am woman.
That had a huge impact on me, as until that point I only considered my competition to be better scientists, and progression or recognition being awarded solely on that basis. When I heard comments around my fellowship being awarded on the basis of political or optical reasons, I found it very unfair. Taking a step back from this, when listening to feedback from the grant agency about the exceptional quality of my scientific proposal and knowing the effort I put in during the two months time it took to write it, I was able to disconnect myself from comments which I attribute to ‘sour grapes’ and an outdated mentality. There will always be situations that can be interpreted as being unfair, I only hope it’s not me causing it or that I have the strength of character to get past it.
Which paper of yours you are the proudest of and why?
The one I’m currently writing – a tutorial review. Being able to bring together a whole subjects worth of science in a comprehensive and easily accessible manner, building interest in the topic and sharing my enthusiasm for it is a great reward for the pain of summarising and coherently bringing together 1’000’s of papers and decades of research!!
Which field of medicinal chemistry do you consider the most promising in the future?
Medicinal chemistry is the start of the drug development process – it is a wonderfully multidisciplinary field of science and needs to solve many problems. I am always keen and motivated to find ways to leverage the work and results generated by medicinal chemistry teams in later stage development and finding technologies that are as applicable to the development chemist, as they are the medicinal chemist, builds in a layer of efficiency and effectiveness that streamlines the drugs development and production. Anything that supports this broadly applicable and scalable technology creation and adoption is going to deliver meaningful results in any organisation.
What would you like to ask from other medicinal chemists?
As a medicinal chemist you have the pressure to deliver to sometimes near impossible timelines, but please take a chance sometime to try biocatalysis and see what it can do for you and your project! You won’t be disappointed :)
What would you guess to be the next major breakthrough in medicinal chemistry?
Utilising the advances we have made in understanding topics such as protein folding and SAR I see the future of rationale based drug design being very bright.
Today, our #Iamamedicinalchemist is professor Adam Nelson from the University of Leeds, UK. Do you know what is the activity-directed synthesis which he is working on? Read more below!
How did you get interested in Chemical Biology?
My interest in the chemistry/biology interface was sparked as a seventeen year-old when I read James Watson’s “Molecular Biology of the Gene”, and was introduced to some of the molecular mechanisms that underpin life. This, and other books, made me realise that the physical sciences can enable fundamental biological discoveries and understanding.
The UK schools system, however, forces people to specialise early. This meant that I had actually dropped biology at the age of 14, and was only taking chemistry, physics and maths in the final two years of school. Fortunately, a degree in natural sciences at Cambridge enabled me to pursue cell biology and biochemistry at university in parallel with the physical sciences.
Where and when did you obtain your PhD diploma?
University of Cambridge, UK. PhD obtained in 1996
What was the topic of your PhD project?
Synthetic organic chemistry
Where did you have your postdoc position?
University of Manchester, UK
Where do you work at the moment and what is your current position?
I’m Professor of Chemical Biology at the University of Leeds, UK. I work within the Astbury Centre at the University of Leeds that brings together about 400 researchers working at the interfaces between biology, chemistry and physics. It’s a remarkable research environment that has enabled me to collaborate on a huge range of exciting problems!
What are your current research interests?
My main interest is in developing efficient chemical approaches that can enable the identification of novel, distinctive and biologically-relevant regions of chemical space.
What do you like most in your job?
Working with intelligent and enthusiastic early career researchers who are willing to embrace exciting new approaches.
What kind of tasks your job includes?
What kind of skills your job requires?
What do you consider your biggest achievement in your scientific career?
I’m proud of many things that my research team has achieved. However, our realisation of a new discovery approach, that we call activity-directed synthesis, is a real highlight for me. Here, the idea is to execute arrays of reactions that have many possible outcomes. We screen the products to identify reactions that yield bioactive structures. But the structures are only revealed after they have been optimised. I like the approach because it uses a completely different reaction toolkit to conventional medicinal chemistry, and you tend to discover functional molecules with unexpected structures!
How many PhD and postdoc students do you have at the moment?
Are you currently looking for a new PhD and postdoc students?
I have about 20 or so co-workers, most of whom are co-supervised with colleagues at Leeds with complementary expertise (particularly colleagues within the Astbury Centre). I’m always looking for talented PhD students, and postdocs who are willing to secure a fellowship. Other postdoc opportunities are advertised formally.
What are the features of a successful PhD student or postdoc?
Which paper of yours you are the proudest of and why?
Probably our paper describing our activity-directed synthesis discovery approach for the first time: Nature Chem. 2014, 6, 872-876
What would you guess to be the next major breakthrough in medicinal chemistry?
The realisation of autonomous discovery platforms in which AI-enabled molecular design, synthesis and evaluation are fully integrated.
The first #Iamamedicinalchemist of 2019 is Maria Duca from the Institute of Chemistry of Nice. She thinks doing research should be also fun. Do you agree?
How did you get interested in Medicinal Chemistry?
I performed my undergraduate studies at the Faculty of Pharmacy of the University of Bologna (Italie) because I had an interest in chemistry and its applications, but without a clear idea of what I really wanted to do later. It was during the second year that I met an organic chemistry professor, Pr. G. Gottarelli, who made me realize how organic chemistry could be fascinating, extremely rich of surprises and discoveries and actually very useful when applied to the research for new drugs. Following courses of medicinal chemistry further consolidated this consciousness, and since then I pursued and realized the objective to work in this field.
Where and when did you obtain your PhD diploma?
I obtained my PhD in Molecular Biochemistry in 2005 in Paris working under the supervision of Dr. Paola Arimondo and Dr. Claude Monneret both at the Pharmacochemistry lab in Institut Curie and in the Biophysics lab in Natural History Museum.
What was the topic of your PhD project?
During my PhD, I worked on the synthesis of new analogs of etoposide, an inhibitor of topoisomerase II, directed against specific sequences on the DNA thanks to their conjugation to triplex-forming oligonucleotides. This was a very original approach for site-specific chemotherapies combining medicinal chemistry with biochemistry, biophysics and cellular biology toward the discovery of potential anticancer agents.
Where did you have your postdoc position?
The experience acquired during undergraduate and graduate studies at the interface of chemistry and biology for the study of conjugations and interactions between small molecules and nucleic acids, led me to Pr. Sydney Hecht lab at the Department of Chemistry of the University of Virginia (USA) for the chemical synthesis of modified tRNAs bearing natural and non-natural amino acids for site-directed mutagenesis of proteins.
Where do you work at the moment and what is your current position? What are your current research interests?
I currently work at the Institute of Chemistry of Nice as a CNRS Research Scientist and I lead a research group entitled “Targeting of Nucleic Acids”. More specifically, I work on the design and synthesis of new small-molecule RNA ligands targeting therapeutically relevant RNA targets such as viral, bacterial and oncogenic RNAs. This is a very fascinating field of medicinal chemistry that has not been sufficiently explored so far but that is in great expansion. There is several challenges in the specific targeting of RNAs using small molecules but also extremely promising perspectives for innovative therapies.
What do you like most in your job?
What I love being a medicinal chemist/chemical biologist is looking for a better understanding of the ways to affect living systems with chemistry. This can lead to interesting discoveries in terms of bioactive compounds but also to new insights about intracellular molecular mechanisms of actions, especially in the field of non-coding RNAs that are at the center of my research projects.
What kind of tasks your job includes?
My work involves a great deal of writing and reading, teaching to students in the lab and of course the never-ending search for financial support. This latter takes a lot of time but is also extremely rewarding since it stimulates the search for new and better ideas, it increases the potential for new collaborations and of course it allows for new recruitments when successful.
What kind of skills your job requires?
First of all, a lot of curiosity and perseverance followed by patience and will to work with colleagues coming from different fields. Second, the ability to communicate clearly and effectively scientific concepts and projects (especially when filling grant applications!).
How many PhD and postdoc students do you have at the moment?
Are you currently looking for a new PhD and postdoc students?
I currently have 3 PhD students and 1 post-doc and I am looking for another post-doc.
What are the features of a successful PhD student or postdoc?
Passion, determination, curiosity and of course the ability to have fun doing research and working with the group.
How would you describe yourself as a supervisor?
I guess we should ask this to my students, but I would say understanding, respectful and flexible even if a little too speedy and thus sometimes lacking patience….
Which scientist do you admire the most and why?
I of course admire a number of scientists excelling for their outstanding discoveries but probably I admire even more the large number of scientists contributing with smaller and less recognized discoveries that are however essential for the most important ones.
Which paper of yours you are the proudest of and why?
A Nucleic Acid Research of 2006 (Nucleic Acids Res. 2006, 34, 1900) which is the most representative paper of my PhD work and includes a lot of the experiments I performed during the PhD.
Which field of medicinal chemistry do you consider the most promising in the future? What would you guess to be the next major breakthrough in medicinal chemistry?
We are currently exploiting only a small portion of existing potential therapeutic targets, thus I guess the most promising field will be the validation of completely new and unexploited targets (such as RNA of course!) combined with innovative chemical approaches to discover effective therapeutic agents. A number of great scientists are currently working toward these directions, so we will likely have major breakthroughs in the near future. Beside this, the precise manipulation of the genome or the specific degradation of relevant targets inside cells probably will lead to revolutionary therapies.
This week's #Iamamedicinalchemist is Matija Sambol from CRO company Fidelta. He is working on the synthesis of new anti-cancer drugs, and you can read more about his work and research interests below.
Where and when did you obtain your PhD diploma?
I’m currently writing my thesis so I will obtain my PhD diploma this year. 
What is the topic of your PhD project?
The topic of my PhD project is new antiproliferative agents based on photochemical formation of quinone methides (QM). The main objective is to synthesize and fully characterize several classes of compounds which contain QM precursor subunits and 1,8-naphthalimide as non-covalent DNA targeting group. The molecules with the best performances in in vitro testing will be screened for antiproliferative activity, with the aim of finding new lead molecules for the drug development.
Where do you work at the moment and what is your current position?
I’m currently working in CRO company Fidelta Ltd. located in Zagreb, Croatia. My current position is associate scientist – medicinal chemist.
What are your current research interests?
I have been so far during my PhD work as well as in medicinal chemistry at my company involved in oncology as therapeutic area, therefore this area I found the most interesting.
How did you get interested in Medicinal Chemistry?
Well, I became interested in chemistry when I was in elementary school thanks to my enthusiastic chemistry teacher and the experiments which we did in classes. I enrolled a secondary chemistry school and after that Faculty of Science, Department of Chemistry in Zagreb. After I obtain my master degree, I started to work at the Ruer Boškovi Institute, and later in Fidelta where I first encountered medical chemistry. How I get interested in medchem? The answer is very simple. If you want to help people and develop a new molecule with druggable properties you have to enroll in medicinal chemistry. In my opinion, medicinal chemistry is characterized by a dual approach of looking at organic chemistry synthesis, while also contemplating biological applications and activity. I'm just at the beginning of the medicinal chemistry road and I hope that I will someday participate in a development of novel biologically active molecules. Someday maybe that active molecule will become a drug which will help and cure a lot of people.
How would you describe yourself as a supervisor?
During my postgraduate study I have supervised undergraduate students in their experimental part of organic chemistry and I have always been objective, fair, easy to approach and willing to help each student in their progress.
What is the most embarrassing thing you did in the lab while doing experiments?
The most embarrassing thing that happened to me in the lab is the neutralisation reaction with sodium hydrogencarbonate. I bet you all know how things can get when you don’t add something portionwise…
Which scientist do you admire the most and why?
I will pick two scientist that I admire the most. The first one is Vladimir Prelog who was Croatian organic chemist. Vladimir Prelog received the Nobel Prize in chemistry (1975) for his research in the area of organic molecules stereochemistry and reactions. If we look outside the box, we can imagine how stereochemistry is important for drug discovery and also for the interaction of all chiral organic molecules. Therefore, in my opinion Vladimir Prelog had a major importance in drug discovery at the very beginning. The second one I admire is also Croatian chemist - Lavoslav Ruži ka. Ruži ka was also a Nobel Prize laureate. His research interests were in the field of chemistry of natural products.
What do you like the most about your job?
Creativity, diversity and interdisciplinary approach at my job are the most precious values!
What kind of task your job includes?
The most of the working time I spend in the lab and I love it! The tasks in a lab usually involves organic synthesis and isolation of the high purity target molecules. The molecules are usually obtained using different synthetic transformations and functional group inter-conversions. Furthermore, I’m also performing synthesis of an advanced intermediates, optimisation of reaction conditions, larger compound quantities for in vivo studies and any other request from milligram to gram scale. Modern techniques such as GC-MS, UPLC-MS and spectroscopic techniques are great help in doing the synthesis. Also, I daily update and record all of my data in e-lab notebook and perform NMR structural studies of synthetized compounds. Most of the projects that I was working on demanded the weekly update so I also prepared presentations about my work for the clients.
What kind of skills your job requires?
From a professional standpoint, the skills that are required for easier and better work is a good organic synthesis knowledge as well as good handling with the lab equipment and instruments as well as handling spectroscopic data like mass spectroscopy and NMR. Also, a good teamwork and communication skills are nothing less important for achieving a desired result.
Which field of medicinal chemistry do you consider the most promising in the future?
In my opinion, one of the most promising fields of medicinal chemistry is immuno-oncology since cancer is a widespread, vicious disease and is one of the leading causes of death in the world. Immuno-oncology is using a unique approach that uses the body's immune system to fight cancer and for that reason it changes the standard of cancer patient’s care, paradigm of cancer treatments and also the drug development. In addition, a lot of pharma companies are entering the field of immuno-oncology.
