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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{Nash:2019:10.1242/bio.037762,
author = {Nash, A and Urdaneta, Mignini G and Beaghton, A and Hoermann, A and Papathanos, P and Christophides, G and Windbichler, N},
doi = {10.1242/bio.037762},
journal = {Biology Open},
title = {Integral Gene Drives for population replacement},
url = {http://dx.doi.org/10.1242/bio.037762},
volume = {8},
year = {2019}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - A first generation of CRISPR-based gene drives has now been tested in the laboratory in a number of organisms, including malaria vector mosquitoes. Challenges for their use in the area-wide genetic control of vector-borne disease have been identified, including the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. We have evaluated theoretically the concept of integral gene drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including drive and anti-pathogen effector elements directly embedded within endogenous genes – an arrangement that in theory allows targeting functionally conserved coding sequences without disrupting their function. Autonomous and non-autonomous IGD strains could be generated, optimized, regulated and imported independently. We performed quantitative modeling comparing IGDs with classical replacement drives and show that selection for the function of the hijacked host gene can significantly reduce the establishment of resistant alleles in the population, while drive occurring at multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target site variation. IGD thus has potential as a more durable and flexible population replacement strategy.
AU  - Nash,A
AU  - Urdaneta,Mignini G
AU  - Beaghton,A
AU  - Hoermann,A
AU  - Papathanos,P
AU  - Christophides,G
AU  - Windbichler,N
DO  - 10.1242/bio.037762
PY  - 2019///
SN  - 2046-6390
TI  - Integral Gene Drives for population replacement
T2  - Biology Open
UR  - http://dx.doi.org/10.1242/bio.037762
UR  - http://hdl.handle.net/10044/1/66490
VL  - 8
ER  -