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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{Hammond:2017:10.1371/journal.pgen.1007039,
author = {Hammond, AM and Kyrou, K and Bruttini, M and North, A and Galizi, R and Karlsson, X and Kranjc, N and Carpi, FM and D'Aurizio, R and Crisanti, A and Nolan, T},
doi = {10.1371/journal.pgen.1007039},
journal = {PLoS Genetics},
title = {The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito},
url = {http://dx.doi.org/10.1371/journal.pgen.1007039},
volume = {13},
year = {2017}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Gene drives have enormous potential for the control of insect populations of medical and agricultural relevance. By preferentially biasing their own inheritance, gene drives can rapidly introduce genetic traits even if these confer a negative fitness effect on the population. We have recently developed gene drives based on CRISPR nuclease constructs that are designed to disrupt key genes essential for female fertility in the malaria mosquito. The construct copies itself and the associated genetic disruption from one homologous chromosome to another during gamete formation, a process called homing that ensures the majority of offspring inherit the drive. Such drives have the potential to cause long-lasting, sustainable population suppression, though they are also expected to impose a large selection pressure for resistance in the mosquito. One of these population suppression gene drives showed rapid invasion of a caged population over 4 generations, establishing proof of principle for this technology. In order to assess the potential for the emergence of resistance to the gene drive in this population we allowed it to run for 25 generations and monitored the frequency of the gene drive over time. Following the initial increase of the gene drive we observed a gradual decrease in its frequency that was accompanied by the spread of small, nuclease-induced mutations at the target gene that are resistant to further cleavage and restore its functionality. Such mutations showed rates of increase consistent with positive selection in the face of the gene drive. Our findings represent the first documented example of selection for resistance to a synthetic gene drive and lead to important design recommendations and considerations in order to mitigate for resistance in future gene drive applications.
AU  - Hammond,AM
AU  - Kyrou,K
AU  - Bruttini,M
AU  - North,A
AU  - Galizi,R
AU  - Karlsson,X
AU  - Kranjc,N
AU  - Carpi,FM
AU  - D'Aurizio,R
AU  - Crisanti,A
AU  - Nolan,T
DO  - 10.1371/journal.pgen.1007039
PY  - 2017///
SN  - 1553-7390
TI  - The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito
T2  - PLoS Genetics
UR  - http://dx.doi.org/10.1371/journal.pgen.1007039
UR  - http://hdl.handle.net/10044/1/51584
VL  - 13
ER  -