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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{Kylilis:2019:10.1021/acssensors.8b01163,
author = {Kylilis, N and Riangrungroj, P and Lai, H-E and Salema, V and Fernández, LÁ and Stan, G-B and Freemont, PS and Polizzi, KM},
doi = {10.1021/acssensors.8b01163},
journal = {ACS Sensors},
pages = {370--378},
title = {Whole-cell biosensor with tuneable limit of detection enables low-cost agglutination assays for medical diagnostic applications},
url = {http://dx.doi.org/10.1021/acssensors.8b01163},
volume = {4},
year = {2019}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Whole-cell biosensors can form the basis of affordable, easy-to-use diagnostic tests that can be readily deployed for point-of-care (POC) testing, but to date, the detection of analytes such as proteins that cannot easily diffuse across the cell membrane has been challenging. Here we developed a novel biosensing platform based on cell agglutination using an E. coli whole-cell biosensor surface-displaying nanobodies which bind selectively to a target protein analyte. As a proof-of-concept, we show the feasibility of this design can detect a model analyte at nanomolar concentrations. Moreover, we show that the design architecture is flexible by building assays optimized to detect a range of model analyte concentrations using straight-forward design rules and a mathematical model. Finally, we re-engineer our whole-cell biosensor for the detection of a medically relevant biomarker by the display of two different nanbodies against human fibrinogen and demonstrate a detection limit as low as 10 pM in diluted human plasma. Overall, we demonstrate that our agglutination technology fulfills the requirement of POC testing by combining low-cost nanobody production, customizable detection range and low detection limits. This technology has the potential to produce affordable diagnostics for field-testing in the developing world, emergency or disaster relief sites as well as routine medical testing and personalized medicine.
AU  - Kylilis,N
AU  - Riangrungroj,P
AU  - Lai,H-E
AU  - Salema,V
AU  - Fernández,LÁ
AU  - Stan,G-B
AU  - Freemont,PS
AU  - Polizzi,KM
DO  - 10.1021/acssensors.8b01163
EP  - 378
PY  - 2019///
SN  - 2379-3694
SP  - 370
TI  - Whole-cell biosensor with tuneable limit of detection enables low-cost agglutination assays for medical diagnostic applications
T2  - ACS Sensors
UR  - http://dx.doi.org/10.1021/acssensors.8b01163
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30623662
UR  - http://hdl.handle.net/10044/1/65633
VL  - 4
ER  -