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Yusuf Hamied Department of Chemistry

 

Our dear friend and colleague Chris Abell died suddenly at the age of 62 on Monday the 26th of October. Chris has been a member of the Department since his undergraduate days in the late 70s. He joined the academic staff in 1984 and soon become a major figure in the area of biological chemistry.  Chris was a pioneer in the field of fragment-based drug discovery, a successful entrepreneur, a founding director of Cambridge Enterprise, and the University’s first Director of Postdoctoral Affairs. Latterly he has been the University's Pro-Vice Chancellor for Research, and had been instrumental in preparing the University for next year's REF assessment. Earlier this year he took on an essential role in coordinating the University's response to meet national targets for Covid-19 testing. For a fuller appreciation of the contribution Chris has made, see here.

What we do...

We’ve developed a successful approach to speed up the design of molecules that block the action of enzymes. Many medicines work by blocking enzymes. We are using our approach to make molecules that could lead to new treatments for diseases such as tuberculosis and cystic fibrosis. In our method we use a range of techniques including X-ray crystallography to screen small molecules, called fragments, and learn how they bind to particular enzymes. We use the most promising fragments  to build  or ‘synthesise’ new molecules that bind ever more tightly to the enzyme we want to target. 

In other research, we’ve shown how to use tiny water droplets, called microdroplets, to screen millions of individual cells for biological research. We have also developed ways to create tiny capsules that can carry enzymes or other molecules and deliver these to chosen targets e.g. a plant, human skin or clothing.

We have co-founded three spinout companies to refine and market these products to the pharmaceutical and other industries. 

Fragment based approaches to enzyme inhibition

One of the biggest challenges in biological chemistry is the design of small molecules that interact selectively with macromolecules. We are pioneering the development of the use of fragments to address this challenge. This approach involves close synergistic interaction between synthetic organic chemistry, biophysics and structural biology. We are using fragment-based methods to identify inhibitors of enzymes from Mycobacterium tuberculosis, and to develop small molecules that modulate protein-protein interactions. We are also keen to explore new applications for fragments e.g. to identify molecules that modulate the activity of riboswitches, and to assign function to orphan proteins.

Microdroplets in microfluidics

Our second major area of research is to develop the use of microdroplets in microfluidics as a novel experimental platform for biological chemistry. This research is highly interdisciplinary and involves biological chemistry, microfluidics, nanofabrication, laser spectroscopy and mass spectrometry. We are particularly interested in looking at cells in droplets, e.g. bacteria to study quorum sensing, algae for bio-fuel development.

Publications

A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death.
DE Scott, NJ Francis-Newton, ME Marsh, AG Coyne, G Fischer, T Moschetti, AR Bayly, TD Sharpe, KT Haas, L Barber, CR Valenzano, R Srinivasan, DJ Huggins, M Lee, A Emery, B Hardwick, M Ehebauer, C Dagostin, A Esposito, L Pellegrini, T Perrior, G McKenzie, TL Blundell, M Hyvönen, J Skidmore, AR Venkitaraman, C Abell
– Cell Chem Biol
(2021)
28,
835
Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site.
V Mendes, SR Green, JC Evans, J Hess, M Blaszczyk, C Spry, O Bryant, J Cory-Wright, DS-H Chan, PHM Torres, Z Wang, N Nahiyaan, S O'Neill, S Damerow, J Post, T Bayliss, SL Lynch, AG Coyne, PC Ray, C Abell, KY Rhee, HIM Boshoff, CE Barry, V Mizrahi, PG Wyatt, TL Blundell
– Nature Communications
(2021)
12,
143
Chemical validation of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase using fragment linking and CRISPR interference
J El Bakali, M Blaszczyk, J Evans, J Boland, W McCarthy, M Dias, A Coyne, V Mizrahi, T Blundell, C Abell, C Spry
(2020)
Fragment-Based Design of Mycobacterium tuberculosis InhA Inhibitors (vol 63, pg 4749, 2020)
M Sabbah, V Mendes, RG Vistal, DMG Dias, M Záhorszká, K Mikušová, J Korduláková, AG Coyne, TL Blundell, C Abell
– Journal of Medicinal Chemistry
(2020)
63,
8650
Fragment-based discovery of a new class of inhibitors targeting mycobacterial tRNA modification.
SE Thomas, AJ Whitehouse, K Brown, S Burbaud, JM Belardinelli, J Sangen, R Lahiri, MDJ Libardo, P Gupta, S Malhotra, HIM Boshoff, M Jackson, C Abell, AG Coyne, TL Blundell, RA Floto, V Mendes
– Nucleic Acids Res
(2020)
48,
8099
Using a Fragment-Based Approach to Identify Alternative Chemical Scaffolds Targeting Dihydrofolate Reductase from Mycobacterium tuberculosis
JA Ribeiro, A Hammer, GA Libreros-Zúñiga, SM Chavez-Pacheco, P Tyrakis, GS de Oliveira, T Kirkman, J El Bakali, SA Rocco, ML Sforça, R Parise-Filho, AG Coyne, TL Blundell, C Abell, MVB Dias
– ACS Infect Dis
(2020)
6,
2192
Spatially Controlled Supramolecular Polymerization of Peptide Nanotubes by Microfluidics
A Méndez‐Ardoy, A Bayón‐Fernández, Z Yu, C Abell, JR Granja, J Montenegro
– Angewandte Chemie
(2020)
132,
6969
Viscoelastic Hydrogel Microfibers Exploiting Cucurbit[8]uril Host-Guest Chemistry and Microfluidics.
Z-J Meng, J Liu, Z Yu, H Zhou, X Deng, C Abell, OA Scherman
– ACS Appl Mater Interfaces
(2020)
12,
17929
Fragment-based design of mycobacterium tuberculosis inha inhibitors
M Sabbah, V Mendes, RG Vistal, DMG Dias, M Záhorszká, K Mikušová, J Korduláková, AG Coyne, TL Blundell, C Abell
– Journal of Medicinal Chemistry
(2020)
63,
4749
Spatially Controlled Supramolecular Polymerization of Peptide Nanotubes by Microfluidics.
A Méndez-Ardoy, A Bayón-Fernández, Z Yu, C Abell, JR Granja, J Montenegro
– Angewandte Chemie - International Edition
(2020)
59,
6902
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Research Group

Research Interest Group

Telephone number

01223 336405

Email address

ca26@cam.ac.uk