Research

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Synthetic Biology underpins advances in the bioeconomy

Biological systems - including the simplest cells - exhibit a broad range of functions to thrive in their environment. Research in the Imperial College Centre for Synthetic Biology is focused on the possibility of engineering the underlying biochemical processes to solve many of the challenges facing society, from healthcare to sustainable energy. In particular, we model, analyse, design and build biological and biochemical systems in living cells and/or in cell extracts, both exploring and enhancing the engineering potential of biology. 

As part of our research we develop novel methods to accelerate the celebrated Design-Build-Test-Learn synthetic biology cycle. As such research in the Centre for Synthetic Biology highly multi- and interdisciplinary covering computational modelling and machine learning approaches; automated platform development and genetic circuit engineering ; multi-cellular and multi-organismal interactions, including gene drive and genome engineering; metabolic engineering; in vitro/cell-free synthetic biology; engineered phages and directed evolution; and biomimetics, biomaterials and biological engineering.

Publications

Citation

BibTex format

@article{MacDonald:2016:10.1073/pnas.1525308113,
author = {MacDonald, JT and Kabasakal, BV and Godding, D and Kraatz, S and Henderson, L and Barber, J and Freemont, PS and Murray, JW},
doi = {10.1073/pnas.1525308113},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
pages = {10346--10351},
title = {Synthetic beta-solenoid proteins with the fragment-free computational design of a beta-hairpin extension},
url = {http://dx.doi.org/10.1073/pnas.1525308113},
volume = {113},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The ability to design and construct structures with atomic level precisionis one of the key goals of nanotechnology. Proteins offer anattractive target for atomic design, as they can be synthesized chemicallyor biologically, and can self-assemble. However the generalizedprotein folding and design problem is unsolved. One approach tosimplifying the problem is to use a repetitive protein as a scaffold.Repeat proteins are intrinsically modular, and their folding and structuresare better understood than large globular domains. Here, wehave developed a new class of synthetic repeat protein, based onthe pentapeptide repeat family of beta-solenoid proteins. We haveconstructed length variants of the basic scaffold, and computationallydesigned de novo loops projecting from the scaffold core. Theexperimentally solved 3.56 A resolution crystal structure of one designedloop matches closely the designed hairpin structure, showingthe computational design of a backbone extension onto a syntheticprotein core without the use of backbone fragments from knownstructures. Two other loop designs were not clearly resolved in thecrystal structures and one loop appeared to be in an incorrect conformation.We have also shown that the repeat unit can accommodatewhole domain insertions by inserting a domain into one of the designedloops.
AU  - MacDonald,JT
AU  - Kabasakal,BV
AU  - Godding,D
AU  - Kraatz,S
AU  - Henderson,L
AU  - Barber,J
AU  - Freemont,PS
AU  - Murray,JW
DO  - 10.1073/pnas.1525308113
EP  - 10351
PY  - 2016///
SN  - 1091-6490
SP  - 10346
TI  - Synthetic beta-solenoid proteins with the fragment-free computational design of a beta-hairpin extension
T2  - Proceedings of the National Academy of Sciences of the United States of America
UR  - http://dx.doi.org/10.1073/pnas.1525308113
UR  - http://hdl.handle.net/10044/1/37591
VL  - 113
ER  -
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