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Research

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{McFarlane:2019:10.1073/pnas.1906722116,
author = {McFarlane, C and Shah, N and Kabasakal, B and Echeverria, B and Cotton, C and Bubeck, D and Murray, J},
doi = {10.1073/pnas.1906722116},
journal = {Proceedings of the National Academy of Sciences of USA},
pages = {20984--20990},
title = {Structural basis of light-induced redox regulation in the Calvin-Benson cycle in cyanobacteria},
url = {http://dx.doi.org/10.1073/pnas.1906722116},
volume = {116},
year = {2019}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Plants, algae, and cyanobacteria fix carbon dioxide to organic carbon with the Calvin-Benson (CB) cycle. Phosphoribulokinase (PRK) and glyceraldehyde 3 phosphate dehydrogenase (GAPDH) are essential Calvin-Benson cycle enzymes that control substrate availability for the carboxylation enzyme Rubisco. PRK consumes ATP to produce the Rubisco substrate ribulose bisphosphate (RuBP). GAPDH catalyses the reduction step of the CB cycle with NADPH to produce the sugar, glyceraldehyde 3-phosphate (GAP), which is used for regeneration of RuBP and is the main exit point of the cycle. GAPDH and PRK are co-regulated by the redox state of a conditionally disordered protein CP12, which forms a ternary complex with both enzymes. However, the structural basis of Calvin-Benson cycle regulation by CP12 is unknown. Here we show how CP12 modulates the activity of both GAPDH and PRK. Using thermophilic cyanobacterial homologues, we solve crystal structures of GAPDH with different cofactors and CP12 bound, and the ternary GAPDH-CP12-PRK complex by electron cryo-microscopy, we reveal that formation of the N-terminal disulfide pre-orders CP12 prior to binding the PRK active site, which is resolved in complex with CP12. We find that CP12 binding to GAPDH influences substrate accessibility of all GAPDH active sites in the binary and ternary inhibited complexes. Our structural and biochemical data explain how CP12 integrates responses from both redox state and nicotinamide dinucleotide availability to regulate carbon fixation.
AU  - McFarlane,C
AU  - Shah,N
AU  - Kabasakal,B
AU  - Echeverria,B
AU  - Cotton,C
AU  - Bubeck,D
AU  - Murray,J
DO  - 10.1073/pnas.1906722116
EP  - 20990
PY  - 2019///
SN  - 0027-8424
SP  - 20984
TI  - Structural basis of light-induced redox regulation in the Calvin-Benson cycle in cyanobacteria
T2  - Proceedings of the National Academy of Sciences of USA
UR  - http://dx.doi.org/10.1073/pnas.1906722116
UR  - https://www.pnas.org/content/116/42/20984/
UR  - http://hdl.handle.net/10044/1/73637
VL  - 116
ER  -