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 fumehood …. 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.

Where and when did you obtain your PhD diploma?

I obtained my PhD in “Chemical and Pharmaceutical Sciences” at the University of Siena, Italy in the group of Professor Maurizio Botta. It was the beginning of 2017.

Where are you currently working and what is your current position?

I am currently working for the French company Discngine, in Paris. Discngine develops and provides state-of-the-art IT solutions, mainly for customers involved in life science R&D.

The title of my position is “Senior Consultant”, which, even if it does not seem to tell much, is a pretty good description of what my duties are- helping our customers with, well, a little bit of everything!

What do you like best about your work?

There are multiple aspects I love about my work. For starters, it is never boring! I have the possibility to help our customers in many different areas: from designing a custom solution to handling the administration of an application, to give training on various software, to provide scientific and technical support, to suggest and implement new ways for integration and automation… as I said – a bit of everything.

Another aspect I really like about my job is that it gives me the possibility to interact with many smart and talented people, both co-workers and customers. This often results in producing enriching experiences, allowing me to continuously grow.

Finally, it is really rewarding when I see a customer heavily relying on a piece of work I have done, or helped with. It really shows how much important what we do is.

What kind of tasks does your work involve?

See the previous answer for some examples. More in general, the kind of tasks my work involves are all around the ideation, design, implementation, management, and maintenance of custom IT solutions deployed at customers’ sites. All of this without forgetting the “human factors” as engagement and support of the user community.

What kind of skills does your work require?

My work requires a broad range of competencies. Of course, there is the need for a solid scientific and technical base, but that’s not all. Particularly important skills are also in presentation, project management and people management. It is important to have the capability to quickly grasp - and keep in mind - the “big picture”, so that one can better proceed with all the steps I have mentioned in the previous answer. Mental elasticity is finally crucial; not only is the fundamental to understand the needs, but also what is required to adapt a project when it has already started. In a real-world scenario, we need to be prepared to navigate through an ever-changing landscape of possibilities. Be able to steer in time is the key between success and failure.

What are the features of a successful PhD student or postdoc?

That depends on what one intends with “successful”. Success and sense of achievement are strictly personal feelings. Therefore, my answer here is based purely on my personal idea of success – which, in the case of a PhD student or postdoc, is to put themselves in the best conditions to proceed towards what they would like to do with their next steps. Based on such premise, I would say that to be successful they should be able to not think only about science. They should be able to think about their career path, to create opportunities for themselves, to not waste any occasion to interact with other scientists as well as not-scientists. So, translated into feature, I think that I could say: “communicative planner”.

How would you describe yourself as a supervisor?

I think that many of the ex-students I supervised while working at the university would agree on these 3 words: “tough but fair”. I believe it fits.

Which field of medicinal chemistry do you consider the most promising for the future?

The usage of AI-assisted computational methods to reliably predict 3D protein structures.

Case Study

Mutants of RAS are major oncogenes and are prevalent in many human cancers, however efforts to develop drugs that directly inhibit the corresponding constitutively active RAS proteins have been unsuccessful so far, although there are promising new findings for KRas-G12C covalent inhibitors. We focused on SOS1, the guanine nucleotide exchange factor (GEF), and an activator of RAS. We identified good starting points for medicinal chemistry activities using both high-throughput and fragment screens. Initial optimizations resulted in the discovery of the first nanomolar SOS1 inhibitors, which effectively downregulated active RAS in tumour cells. Here, the key findings on our path to identifying novel potent and cellular active small molecule inhibitors will be described. These inhibitors efficiently disrupted the interaction between KRAS and its exchange factor SOS1, this mode of action was confirmed by a series of biophysical techniques. The binding sites, mode of action and selectivity were elucidated using crystal structures of KRASG12C–SOS1, SOS1 and SOS2. By preventing formation of the KRAS–SOS1 complex, these inhibitors block the reloading of KRAS with GTP and, therefore, showed antiproliferative activity. Our probe BAY-293 selectively inhibited the KRAS–SOS1 interaction with an IC50 of 21 nM and is a valuable chemical probe for further investigations. In cells with wild-type KRAS the complete inhibition of the RAS–RAF–MEK–ERK pathway was observed. In a mutant KRAS cell line, SOS1 inhibition resulted in a reduction of pERK activity by 50%. Together, the data indicate that inhibition of GEFs may represent a new viable approach for targeting RAS-driven tumours.

Round Table Discussion

Join our panel of various scientists to hear about their experience as foreigner. Ask questions and learn the tips & tricks to succeed in moving to, working, and living in Germany.

• Eleonora Diamanti (Helmholtz Institute for Pharmaceutical Research Saarland, Germany)
• Louise Eagling (Nuvisan, Germany)
• Dr Keith Graham (Boehringer Ingelheim, Germany) 
• Katarina Iric (DyNAbind, Germany)
• Andrea Unzue-Lopez (Merck, Germany)

Register for free here: Webinar Registration - Zoom

#GDCh (MedChem Division), #NextGenMedChem.

The rapid emergence of antibiotic resistance (AMR) in bacteria is one of the most pressing global health threats. Despite its significance, the potential impact of this phenomenon remains largely underappreciated by a large portion of the population. The recent Covid-19 pandemic has further intensified the use of antibiotics, often without clinical justification, which is expected to further impact on future AMR statistics. In Europe alone, >33,000 deaths per year are attributable to resistant infections (700,000 world-wide), resulting in a substantial clinical and financial burden on healthcare providers, clinicians, patients, and patients’ families. The cost associated with the management of these infections is estimated at $ 11.3 billion. If we do not strengthen our efforts to stem the tide of antimicrobial resistance, it is predicted that by 2050 antibiotic resistant infections may cause 10 million deaths worldwide.

Fortunately, many academic groups and a small number of biotech companies, have chosen to take up the exciting challenge of replenishing the antibiotic development pipeline with innovative molecules. Experts in drug discovery and microbiology will talk about their recent advances in presentations targeting a multidisciplinary audience.

Confirmed speakers

• Dr Florence Séjourné, Beam Alliance, France
• Dr Giulia Manina, Institut Pasteur Paris, France
• Prof. Paul Hergenrother, University of Illinois, United States
• Dr Glenn Dale, Bioversys, Basel, Switzerland
• Dr Robert Bates, GSK, Tres Cantos, Spain
• Prof. Klass Martinus Pos, Goethe University Frankfurt, Germany
• Dr Tim Opperman, Microbiotix, Massachusetts, United States
• Dr Kevin Pethe, Nanyang Technological University, Singapour
• Dr Cédric Couturier, Evotec, France
• Prof. Paul Race, Bristol University, United Kingdom
• Prof. Michel Arthur, Centre de Recherche des Cordeliers, Paris
• Dr David Davies, Antabio, France
• Dr Garrett Moraski, Montana State University, United States

Registration fee: 25€
Contact: amrmeeting@sct-asso.fr
Website: click here
Registration link: click here

VIRTUAL - 3^rd RSC / SCI Symposium on Antimicrobial Drug Discovery

15^th and 16^th November 2021

Last chance to register

Website:  https://www.rscbmcs.org/events/antimicrobial/   

Synopsis:  Coinciding with WHO’s World Antibiotics Awareness week, this two-day meeting will examine the latest advances in antimicrobial drug discovery from a medicinal chemist’s perspective, focusing on the particular challenges associated with developing antimicrobials whilst also showcasing emerging strategies for tackling infection.

5^th RSC / DMDG / DMG New Perspectives in DMPK   

22^nd and 23^rd February 2022, Liverpool, UK

The call for abstracts will close on 25^th November (oral) and 13^th January 2022 (oral)

Website:   https://www.rscbmcs.org/events/dmpk/   

Synopsis:    Members from across the DMPK research community are encouraged to join colleagues from across academic, industrial, and third-sector institutions and contribute to the ongoing discussion, evolution and application of DMPK in various scenarios.

Fragments VIII:  8^th RSC-BMCS Fragment-based Drug Discovery meeting

27^thand 28^th March 2022, Churchill College, Cambridge

Registration is now open

Website:  https://www.rscbmcs.org/events/fragments/

Synopsis:  The aim of the meeting is to continue the focus on case studies in Fragment-based Drug Discovery that have delivered compounds to late-stage medicinal chemistry, preclinical or clinical programmes. Over three-quarters of the presentations will be focused on case studies.