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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{Ukegbu:2020:10.1073/pnas.1919709117,
author = {Ukegbu, CV and Giorgalli, M and Tapanelli, S and Rona, LDP and Jaye, A and Wyer, C and Angrisano, F and Christophides, G and Vlachou, D},
doi = {10.1073/pnas.1919709117},
journal = {Proceedings of the National Academy of Sciences of USA},
pages = {7363--7373},
title = {PIMMS43 is required for malaria parasite immune evasion and sporogonic development in the mosquito vector},
url = {http://dx.doi.org/10.1073/pnas.1919709117},
volume = {117},
year = {2020}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - After being ingested by a female Anopheles mosquito during a bloodmeal on an infected host, and before they can reach the mosquito salivary glands to be transmitted to a new host, Plasmodium parasites must establish an infection of the mosquito midgut in the form of oocysts. To achieve this, they must first survive a series of robust innate immune responses that take place prior to, during, and immediately after ookinete traversal of the midgut epithelium. Understanding how parasites may evade these responses could highlight new ways to block malaria transmission. We show that an ookinete and sporozoite surface protein designated as PIMMS43 (Plasmodium Infection of the Mosquito Midgut Screen 43) is required for parasite evasion of the Anopheles coluzzii complement-like response. Disruption of PIMMS43 in the rodent malaria parasite Plasmodium berghei triggers robust complement activation and ookinete elimination upon mosquito midgut traversal. Silencing components of the complement-like system through RNAi largely restores ookinete-to-oocyst transition but oocysts remain small in size and produce a very small number of sporozoites that additionally are not infectious, indicating that PIMMS43 is also essential for sporogonic development in the oocyst. Antibodies that bind PIMMS43 interfere with parasite immune evasion when ingested with the infectious blood meal and significantly reduce the prevalence and intensity of infection. PIMMS43 genetic structure across African Plasmodium falciparum populations indicates allelic adaptation to sympatric vector populations. These data add to our understanding of mosquito–parasite interactions and identify PIMMS43 as a target of malaria transmission blocking.
AU  - Ukegbu,CV
AU  - Giorgalli,M
AU  - Tapanelli,S
AU  - Rona,LDP
AU  - Jaye,A
AU  - Wyer,C
AU  - Angrisano,F
AU  - Christophides,G
AU  - Vlachou,D
DO  - 10.1073/pnas.1919709117
EP  - 7373
PY  - 2020///
SN  - 0027-8424
SP  - 7363
TI  - PIMMS43 is required for malaria parasite immune evasion and sporogonic development in the mosquito vector
T2  - Proceedings of the National Academy of Sciences of USA
UR  - http://dx.doi.org/10.1073/pnas.1919709117
UR  - https://www.pnas.org/content/117/13/7363/
UR  - http://hdl.handle.net/10044/1/78049
VL  - 117
ER  -