Edward Tate is currently a Senior Lecturer in Chemical Biology at Imperial College London. Following undergraduate studies at the University of Durham, he gained his PhD with Prof. Steve Ley FRS at the University of Cambridge and then worked with Prof. Sam Zard at Ecole Polytechnique (Paris) as an 1851 Research Fellow. Following postdoctoral research in molecular microbiology at the Pasteur Institute in Paris and in chemical biology at Imperial College he was awarded an independent BBSRC David Phillips Research Fellowship in 2006, and in 2010 he was appointed to his current position in the Department of Chemistry. His research group of over 20 researchers is engaged in multiple aspects of the design and application of chemical approaches to understanding living systems, with an emphasis on the roles of protein modification in disease. He has published around 40 papers and patents in the fields of organic synthesis, medicinal chemistry and chemical biology. Ed is also an integral member of the Institute of Chemical Biology at Imperial College, where he co-convenes the first Imperial MRes in Drug Discovery and Development, a one year course that arms students with the knowledge and insight needed to launch a career in the rapidly evolving landscape of contemporary medicinal chemistry.
The proteome is an extremely dynamic and versatile entity, due in no small part to post- and co-translational modification (PTM) of proteins. Every pathway in the cell is mediated and/or regulated through PTM at some level, and these phenomena emerge from a complex network of enzyme-protein substrate interactions. My group is fascinated by the ways in which organic chemistry can be brought to bear on the formidable challenge of mapping, understanding and manipulating these PTM networks, both to reveal the basic biology of living systems and to leverage new data on druggable targets inside the cell. The main projects in our lab are dedicated to developing novel reagents for bioorthogonal ligation, and applying them to profile the targets of PTM and to profile the activity of enzymes that mediate PTM. For example, we have recently demonstrated new approaches for labelling protein lipidation in living cells, and have profiled the downstream targets of prenyl transferase inhibitors and the impact of genetic defects on protein prenylation in vivo in disease models.
In collaboration with researchers at Imperial we have also described the first example of activity-based protein profiling (ABPP) in the hospital superbug Clostridium difficile, using this powerful approach to identify and characterise the function of key proteases that remodel the surface layer of the organism. Our second major area of activity is in developing inhibitors for enzymes implicated in mis-regulated PTM in disease, and as drug targets in important pathogens such as the protozoan parasites that cause malaria and leishmaniasis. In collaborative drug discovery projects we have reported the first drug-like inhibitors of the enzyme NMT (N-myristoyl transferase) in the malaria parasite, and the first crystal structure of this enzyme in Leishmania donovani. The final area we are involved in is the engineering of peptide and peptidomimetic scaffolds for the disruption of protein-protein interactions (PPIs) related to PTM. For example, we hav e re-engineered macrocyclic cystine-knot microprotein scaffolds for selective inhibition of a range of therapeutically important proteases, and explored the dynamics of an essential PPI in the motor that drives red blood cell invasion by the malaria parasite.
• T. H. T. Dang, L. de la Riva, R. P. Fagan, W. P. Heal, C. Janoir, Neil F. Fairweather, and E. W. Tate, ‘Chemical probes of surface layer biogenesis in Clostridium difficile’, ACS Chem. Biol., 2010, 5, 279-285.
• A. F. H. Berry, W. P. Heal, Abul K. Tarafder, T. Tolmachova, R. A. Baron, M. C. Seabra and E. W. Tate, “Rapid multi-label detection of geranylgeranylated proteins using bioorthogonal ligation chemistry”, ChemBioChem, 2010, 11, 771-774.
• J. C. Thomas, J. L. Green, R. I. Howson, P. Simpson, D. K. Moss, S. R. Martin, A. A. Holder, E. Cota and E. W. Tate, “Interaction and dynamics of the Plasmodium falciparum MTIP/MyoA complex, a key component of the invasion motor in the malaria parasite”, MolBioSyst, 2010, 6, 494.
• J. A. Brannigan, B. A. Smith, Z. Yu, A. M. Brzozowski, M. R. Hodgkinson, A. Maroof, H. P. Price, F. Meier, R. J. Leatherbarrow, E. W. Tate, D. F. Smith, A. J. Wilkinson ‘N-myristoyl transferase from Leishmania donovani as a Target for Drug Discovery: Structural and Functional Characterisation’, J. Mol. Biol., 2010, 396, 985-999.
• P. Thongyoo, C. Bonomelli, R. J. Leatherbarrow and E. W. Tate, “Potent inhibitors of β-tryptase and human leukocyte elastase based on the MCoTI-II scaffold”, J. Med. Chem., 2009, 52, 6197-6200.
• W. P. Heal, S. R. Wickramasinghe, P. W. Bowyer, A. A. Holder, D. F. Smith, R. J. Leatherbarrow and E. W. Tate, “Site-specific N-terminal labelling of proteins in vitro and in vivo using N-myristoyl transferase and bioorthogonal ligation chemistry”, Chem. Commun., 2008, 4, 480-482.
Information and contact
Dr Edward Tate
Tel: +44 (0)20 7594 3752
Personal website: www3.imperial.ac.uk/people/e.tate