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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{Wilkinson:2020:10.1128/aac.02129-19,
author = {Wilkinson, MD and Lai, H-E and Freemont, PS and Baum, J},
doi = {10.1128/aac.02129-19},
journal = {Antimicrobial Agents and Chemotherapy},
pages = {1--9},
title = {A biosynthetic platform for antimalarial drug discovery},
url = {http://dx.doi.org/10.1128/aac.02129-19},
volume = {64},
year = {2020}
}

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RIS format (EndNote, RefMan)

TY - JOUR
AB - Advances in synthetic biology have enabled production of a variety of compounds using bacteria as a vehicle for complex compound biosynthesis. Violacein, a naturally occurring indole pigment with antibiotic properties, can be biosynthetically engineered in Escherichia coli expressing its non-native synthesis pathway. To explore whether this synthetic biosynthesis platform could be used for drug discovery, here we have screened bacterially-derived violacein against the main causative agent of human malaria, Plasmodium falciparum. We show the antiparasitic activity of bacterially-derived violacein against the P. falciparum 3D7 laboratory reference strain as well as drug-sensitive and resistant patient isolates, confirming the potential utility of this drug as an antimalarial. We then screen a biosynthetic series of violacein derivatives against P. falciparum growth. The demonstrated varied activity of each derivative against asexual parasite growth points to potential for further development of violacein as an antimalarial. Towards defining its mode of action, we show that biosynthetic violacein affects the parasite actin cytoskeleton, resulting in an accumulation of actin signal that is independent of actin polymerization. This activity points to a target that modulates actin behaviour in the cell either in terms of its regulation or its folding. More broadly, our data show that bacterial synthetic biosynthesis could become a suitable platform for antimalarial drug discovery with potential applications in future high-throughput drug screening with otherwise chemically-intractable natural products.
AU - Wilkinson,MD
AU - Lai,H-E
AU - Freemont,PS
AU - Baum,J
DO - 10.1128/aac.02129-19
EP - 9
PY - 2020///
SN - 0066-4804
SP - 1
TI - A biosynthetic platform for antimalarial drug discovery
T2 - Antimicrobial Agents and Chemotherapy
UR - http://dx.doi.org/10.1128/aac.02129-19
UR - https://aac.asm.org/content/early/2020/03/03/AAC.02129-19/article-info
UR - http://hdl.handle.net/10044/1/77366
VL - 64
ER -