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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{Senthivel:2016:10.1038/srep39178,
author = {Senthivel, V and Sturrock, M and Piedrafita, G and Isalan, M},
doi = {10.1038/srep39178},
journal = {Scientific Reports},
title = {Identifying ultrasensitive HGF dose-response functions in a 3D mammalian system for synthetic morphogenesis},
url = {http://dx.doi.org/10.1038/srep39178},
volume = {6},
year = {2016}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Nonlinearresponses  to  signalsarewidespread natural phenomenathat affect  various cellular processes. Nonlinearitycan bea desirable characteristic for engineering living organismsbecause  it  can  lead  to  more  switch-like  responses, similar  to those underlying the wiring inelectronics. Steeperfunctions are described as ultrasensitive, and  can  be  applied  in synthetic  biologyby  using various  techniquesincludingreceptor decoys,   multiple co-operative binding   sites, and sequentialpositive feedbacks. Here,  we  explore  the  inherent  non-linearity  of  a  biological  signaling system  to  identify  functions  that  can  potentially  be  exploited  using  cell  genome engineering.For this,we performed  genome-wide transcription  profilingto  identify genes with ultrasensitiveresponse functionsto Hepatocyte Growth Factor (HGF). Weidentified3,527genesthat react to increasing concentrations of HGF, in Madin-Darby canine kidney (MDCK) cells,grown as cystsin 3D collagen cell culture. By fitting a generic  Hill  function  to  the  dose-responsesof these genes  we obtained  ameasure of the ultrasensitivityofHGF-responsive genes,   identifying   a   subset   with   higher apparent Hill coefficients (e.g. MMP1, TIMP1,SNORD75, SNORD86 andERRFI1). The  regulatory  regions  of  these  genes  are potential candidates  for future engineering of synthetic   mammalian   gene   circuits   requiring   nonlinear   responses   to   HGF signalling.
AU  - Senthivel,V
AU  - Sturrock,M
AU  - Piedrafita,G
AU  - Isalan,M
DO  - 10.1038/srep39178
PY  - 2016///
SN  - 2045-2322
TI  - Identifying ultrasensitive HGF dose-response functions in a 3D mammalian system for synthetic morphogenesis
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/srep39178
UR  - http://hdl.handle.net/10044/1/42705
VL  - 6
ER  -

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