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Department of Chemistry

 

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

Droplet microfluidics for the highly controlled synthesis of branched gold nanoparticles.
S Abalde-Cela, P Taladriz-Blanco, MG de Oliveira, C Abell
– Scientific reports
(2018)
8,
2440
Mass spectrometry for fragment screening
DS-H Chan, AJ Whitehouse, AG Coyne, C Abell
– Essays in biochemistry
(2017)
61,
465
Target identification of $\textit{Mycobacterium tuberculosis phenotypic}$ hits using a concerted chemogenomic, biophysical and structural approach
G Mugumbate, V Mendes, M Blaszczyk, M Sabbah, G Papadatos, J Lelievre, L Ballell, D Barros, C Abell, TL Blundell, JP Overington
– Frontiers in pharmacology
(2017)
8,
681
Effect of DMSO on Protein Structure and Interactions Assessed by Collision-Induced Dissociation and Unfolding.
DS-H Chan, ME Kavanagh, KJ McLean, AW Munro, D Matak-Vinković, AG Coyne, C Abell
– Analytical chemistry
(2017)
89,
9976
Bioinspired supramolecular fibers drawn from a multiphase self-assembled hydrogel
Y Wu, DU Shah, C Liu, Z Yu, J Liu, X Ren, MJ Rowland, C Abell, MH Ramage, OA Scherman
– Proceedings of the National Academy of Sciences
(2017)
114,
8163
Fragment Screening against the EthR–DNA Interaction by Native Mass Spectrometry
DS-H Chan, V Mendes, SE Thomas, BN McConnell, D Matak-Vinković, AG Coyne, TL Blundell, C Abell
– Angewandte Chemie - International Edition
(2017)
56,
7488
Tough Supramolecular Polymer Networks with Extreme Stretchability and Fast Room-Temperature Self-Healing.
J Liu, CSY Tan, Z Yu, N Li, C Abell, OA Scherman
– Advanced materials (Deerfield Beach, Fla.)
(2017)
29,
1605325
Fragment-Sized EthR Inhibitors Exhibit Exceptionally Strong Ethionamide Boosting Effect in Whole-Cell $\textit{Mycobacterium tuberculosis}$ Assays
PO Nikiforov, M Blaszczyk, S Surade, HI Boshoff, A Sajid, V Delorme, N Deboosere, P Brodin, AR Baulard, CE Barry, TL Blundell, C Abell
– ACS Chemical Biology
(2017)
12,
1390
The biochemical properties of the two $\textit{Arabidopsis thaliana}$ isochorismate synthases.
KM Macaulay, GA Heath, A Ciulli, AM Murphy, C Abell, JP Carr, AG Smith
– The Biochemical journal
(2017)
474,
1579
Research data supporting "Structural insights into the EthR-DNA interaction using native mass spectrometry"
D Shiu-Hin Chan, W-G Seetoh, BN McConnell, D Matak-Vinković, SE Thomas, V Mendes, M Blaszczyk, AG Coyne, TL Blundell, C Abell
– Chemical communications (Cambridge, England)
(2017)
53,
3527
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Research Group

Research Interest Group

Telephone number

01223 336405

Email address

ca26@cam.ac.uk