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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{Broedel:2020:10.1126/sciadv.aba2728,
author = {Broedel, A and Rodrigues, R and Jaramillo, A and Isalan, M},
doi = {10.1126/sciadv.aba2728},
journal = {Science Advances},
pages = {1--9},
title = {Accelerated evolution of a minimal 63-amino acid dual transcription factor},
url = {http://dx.doi.org/10.1126/sciadv.aba2728},
volume = {6},
year = {2020}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Transcription factors control gene expression in all life. This raises the question of what is the smallest protein that can support such activity. In nature, Cro from bacteriophage λ is one of the smallest known repressors (66 amino acids; a.a.) and activators are typically much larger (e.g. λ cI, 237 a.a.). Indeed, previous efforts to engineer a minimal activator from λ Cro resulted in no activity in vivo, in cells. In this study, we show that directed evolution results in a new Cro activator-repressor that functions as efficiently as λ cI, in vivo. To achieve this, we develop Phagemid-Assisted Continuous Evolution: PACEmid. We find that a peptide as small as 63 a.a. functions efficiently as an activator and/or repressor. To our knowledge, this is the smallest protein activator that enables polymerase recruitment, highlighting the capacity of transcription factors to evolve from very short peptide sequences.
AU  - Broedel,A
AU  - Rodrigues,R
AU  - Jaramillo,A
AU  - Isalan,M
DO  - 10.1126/sciadv.aba2728
EP  - 9
PY  - 2020///
SN  - 2375-2548
SP  - 1
TI  - Accelerated evolution of a minimal 63-amino acid dual transcription factor
T2  - Science Advances
UR  - http://dx.doi.org/10.1126/sciadv.aba2728
UR  - https://advances.sciencemag.org/content/6/24/eaba2728
UR  - http://hdl.handle.net/10044/1/79209
VL  - 6
ER  -