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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{Fasulo:2019:10.1101/834630,
author = {Fasulo, B and Meccariello, A and Morgan, M and Borufka, C and Papathanos, PA and Windbichler, N},
doi = {10.1101/834630},
title = {A fly model establishes distinct mechanisms for synthetic CRISPR/Cas9 sex distorters},
url = {http://dx.doi.org/10.1101/834630},
year = {2019}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:p>Synthetic sex distorters have recently been developed in the malaria mosquito, relying on endonucleases that target the X-chromosome during spermatogenesis. Although inspired by naturally-occurring traits, it has remained unclear how they function and, given their potential for genetic control, how portable this strategy is across species. We established<jats:italic>Drosophila</jats:italic>models for two distinct mechanisms for CRISPR/Cas9 sex-ratio distortion - “X-shredding” and “X-meddling” - and dissected their target-site requirements and repair dynamics. X-shredding relies on sufficient meiotic activity of the endonuclease to overpower DNA repair and can operate on a single repeat cluster of non-essential sequences. X-meddling by contrast, i.e. targeting putative haplolethal X-linked genes, induced a bias towards males that is coupled to a loss in reproductive output, although a dominant-negative effect may drive the mechanism of female lethality. Our model system will guide the study and the application of sex distorters to medically or agriculturally important insect target species.</jats:p>
AU  - Fasulo,B
AU  - Meccariello,A
AU  - Morgan,M
AU  - Borufka,C
AU  - Papathanos,PA
AU  - Windbichler,N
DO  - 10.1101/834630
PY  - 2019///
TI  - A fly model establishes distinct mechanisms for synthetic CRISPR/Cas9 sex distorters
UR  - http://dx.doi.org/10.1101/834630
ER  -

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