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.
Isothermal DNA amplification using the T4 replisome: circular nicking endonuclease-dependent amplification and primase-based whole-genome amplification.
Y Schaerli, V Stein, MM Spiering, SJ Benkovic, C Abell, F Hollfelder - Nucleic Acids Research (
2010)
38, e201
(DOI:
10.1093/nar/gkq795)
Fluorosurfactants for microdroplets: interfacial tension analysis.
DJ Holt, RJ Payne, WY Chow, C Abell - J Colloid Interface Sci (
2010)
350, 205
(DOI:
10.1016/j.jcis.2010.06.036)
Management of the diffusion of 4-methylumbelliferone across phases in microdroplet-based systems for in vitro protein evolution
N Wu, F Courtois, YG Zhu, J Oakeshott, C Easton, C Abell - Electrophoresis (
2010)
31, 3121
(DOI:
10.1002/elps.201000140)
Application of the interligand Overhauser effect to fragment linking and screening
P Sledz, AW Hung, HL Silvestre, SJ Wen, A Ciulli, TL Blundell, C Abell - ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY (2010) 240
Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology.
AB Theberge, F Courtois, Y Schaerli, M Fischlechner, C Abell, F Hollfelder, WTS Huck - Angew Chem Int Ed Engl (
2010)
49, 5846
(DOI:
10.1002/anie.200906653)
Inhibition of chorismate-utilising enzymes by 2-amino-4-carboxypyridine and 4-carboxypyridone and 5-carboxypyridone analogues
RJ Payne, EMM Bulloch, O Kerbarh, C Abell - Organic and Biomolecular Chemistry (
2010)
8, 3534
(DOI:
10.1039/c004062b)
Hydrophilic PDMS microchannels for high-throughput formation of oil-in-water microdroplets and water-in-oil-in-water double emulsions.
WAC Bauer, M Fischlechner, C Abell, WTS Huck - Lab on a Chip - Miniaturisation for Chemistry and Biology (
2010)
10, 1814
(DOI:
10.1039/c004046k)
Merging microdroplets with laminar flow microfluidics
C Abell, W Huck, D Bratton, G Whyte, L Fidalgo - (2010), 8806758.2
Drugging challenging targets using fragment-based approaches
AG Coyne, DE Scott, C Abell - Curr Opin Chem Biol (
2010)
14, 299
(DOI:
10.1016/j.cbpa.2010.02.010)
A double droplet trap system for studying mass transport across a droplet-droplet interface
YP Bai, XM He, DS Liu, SN Patil, D Bratton, A Huebner, F Hollfelder, C Abell, WTS Huck - Lab on a Chip - Miniaturisation for Chemistry and Biology (
2010)
10, 1281
(DOI:
10.1039/b925133b)
