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Yusuf Hamied Department of Chemistry

 

Professor of Biological Chemistry / Pro-Vice-Chancellor for Research

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

Microdroplets confined assembly of opal composites in dynamic borate ester-based networks
J Zhang, Y Qin, OJ Pambos, J Zhang, S Chen, Z Yu, C Abell
– Chemical Engineering Journal
(2021)
426,
127581
A fragment-based approach to assess the ligandability of ArgB, ArgC, ArgD and ArgF in the L-arginine biosynthetic pathway of Mycobacterium tuberculosis
P Gupta, SE Thomas, SA Zaidan, MA Pasillas, J Cory-Wright, V Sebastián-Pérez, A Burgess, E Cattermole, C Meghir, C Abell, AG Coyne, WR Jacobs, TL Blundell, S Tiwari, V Mendes
– Comput Struct Biotechnol J
(2021)
19,
3491
Droplet-based microfluidic screening and sorting of microalgal populations for strain engineering applications.
Z Yu, K Geisler, T Leontidou, REB Young, SE Vonlanthen, S Purton, C Abell, AG Smith
– Algal Res
(2021)
56,
None
Targeting Mycobacterium tuberculosis CoaBC through Chemical Inhibition of 4′-Phosphopantothenoyl‑l‑cysteine Synthetase (CoaB) Activity
JC Evans, D Murugesan, JM Post, V Mendes, Z Wang, N Nahiyaan, SL Lynch, S Thompson, SR Green, PC Ray, J Hess, C Spry, AG Coyne, C Abell, HIM Boshoff, PG Wyatt, KY Rhee, TL Blundell, CE Barry, V Mizrahi
– ACS Infect Dis
(2021)
7,
1666
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 Chemical Biology
(2021)
28,
1
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)
2020.09.04.280388
Correction to 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
– J Med Chem
(2020)
63,
8650
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 Infectious Diseases
(2020)
6,
2192
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 research
(2020)
48,
8099
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Research Group

Telephone number

01223 336405