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.
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.
One-step fabrication of supramolecular microcapsules from microfluidic droplets
J Zhang, RJ Coulston, ST Jones, J Geng, OA Scherman, C Abell - Science (
2012)
335, 690
(DOI:
10.1126/science.1215416)
Single Molecule Fluorescence under Conditions of Fast Flow
MH Horrocks, H Li, JU Shim, RT Ranasinghe, RW Clarke, WT Huck, C Abell, D Klenerman - Anal Chem (
2012)
84, 179
(DOI:
10.1021/ac202313d)
Rv2607 from Mycobacterium tuberculosis is a pyridoxine 5'-phosphate oxidase with unusual substrate specificity.
EH Mashalidis, T Mukherjee, P Sledź, D Matak-Vinković, H Boshoff, C Abell, CE Barry - PLoS One (
2011)
6, e27643
(DOI:
10.1371/journal.pone.0027643)
Fragment based approach to targeting the Rad51:BRCA2 protein-protein interaction
AG Coyne, DE Scott, C Abell, M Marsh, M Hyvonen, TL Blundell, A Venkitaraman - ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY (2011) 242
Structural investigation of inhibitor designs targeting 3-dehydroquinate dehydratase from the shikimate pathway of Mycobacterium tuberculosis
MV Dias, WC Snee, KM Bromfield, RJ Payne, SK Palaninathan, A Ciulli, NI Howard, C Abell, JC Sacchettini, TL Blundell - Biochem J (
2011)
436, 729
(DOI:
10.1042/BJ20110002)
From crystal packing to molecular recognition: Prediction and discovery of a binding site on the surface of polo-like kinase 1
P Śledź, CJ Stubbs, S Lang, YQ Yang, GJ McKenzie, AR Venkitaraman, M Hyvönen, C Abell - Angew Chem Int Ed Engl (
2011)
50, 4003
(DOI:
10.1002/anie.201008019)
Identification of novel ligands for thiamine pyrophosphate (TPP) riboswitches.
E Cressina, L Chen, M Moulin, FJ Leeper, C Abell, AG Smith - Biochemical Society Transactions (
2011)
39, 652
(DOI:
10.1042/BST0390652)
Enzyme synthesis and activity assay in microfluidic droplets on a chip
N Wu, F Courtois, R Surjadi, J Oakeshott, TS Peat, CJ Easton, C Abell, YG Zhu - Engineering in Life Sciences (
2011)
11, 157
(DOI:
10.1002/elsc.201000043)
Quantitative tracking of the growth of individual algal cells in microdroplet compartments
J Pan, A Stephenson, C Abell - Integr Biol (Camb) (
2011)
241, 1043
(DOI:
10.1039/c1ib00033k)
Controlling the contents of microdroplets by exploiting the permeability of PDMS
JU Shim, SN Patil, JT Hodgkinson, SD Bowden, DR Spring, M Welch, WTS Huck, F Hollfelder, C Abell - Lab on a Chip - Miniaturisation for Chemistry and Biology (
2011)
11, 1132
(DOI:
10.1039/C0LC00615G)
