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Synthetic Biology Approaches to Sensing Pathogenic Viruses and Narcotics

Primary Supervisor: Professor Tim Dafforn, School of Biosciences

Secondary supervisor: Professor James Tucker

PhD project title: Synthetic Biology Approaches to Sensing Pathogenic Viruses and Narcotics

University of Registration: University of Birmingham

Project outline:

Engineering biology and its place in sensing

One of the key attributes of life is the ability to respond to stimuli. Nature has evolved a wide array of molecules, tissues and organs that sense stimuli as diverse as light, taste, pressure, odour, pheromones and drugs. A long-term challenge of Engineering Biology (EB) (also known as synthetic biology) has been to harness these natural systems in order to develop new and improved sensing systems. A facile example being to exploit the sensing proteins in the nose of a sniffer dog that allow it detect narcotics to produce a handheld device that detects narcotics but without the operational limitations of using a dog. Alternatively, one might be able to use cellular receptors to monitor hormones like insulin in order to control a disease.

One way to achieve this involves a “bottom up” approach where individual biological components, or small groups of components, are combined to produce a sensing element. This has the advantage of exploiting the unique capabilities of biological molecules without ethical issues associated with using GM organisms in the environment.

In our laboratory we have assembled and ensemble of methods and component systems that we have shown can be used to produce sensing systems of demonstrable global importance.

Examples of sensing projects that are available in our laboratory:

  • Exploiting nano-encapsulating membrane receptors for detection

In 2009 we developed a novel method to make membrane proteins that nature uses in sensing (1,2). The method (SMALP) uses a polymer to encapsulate a sensing membrane protein complete with it’s surrounding lipid environment. We have shown that this is a generically applicable method that produces very stable and active samples. In this project our aim is exploit these proteins (particularly G-Protein Coupled Receptors (GPCRs) involved in hormone and narcotics sensing) to develop novel sensors that mimic nature. The project will involve extracting these receptors and then developing methods to integrate them into hand-held sensing systems.

  • Exploiting the world’s fastest DNA/RNA detection system

In the past 12 months we have developed a revolutionary new method to detect viral RNA. The method, developed to address a need during the COVID pandemic, is able to detect < 10 copies of the virus/microlitre in less than 5 minutes. The method is not just applicable to COVID detection but also a wide range of other pathogenic viruses including Influenza, Respiratory Syncytial Virus (RSV) and even Ebola. The process exploits some unique properties of restriction endonucleases in order to amplify small amounts of DNA/RNA (3,4). In this project we would aim to build on this success exploring the fundamental biochemistry that underpins the assay (including developing models that allow assays to be designed more effectively). We would also aim to examine how the methods like lateral flow devices could be used to provide a simple way to read the assay. This work would be carried out in close collaboration with researchers in the Queen Elizabeth 2 Hospital in Birmingham ensuring that the resulting assays match real clinical need.

References:

  1. Knowles, T.J., et al., J Am Chem Soc, 2009. 131(22): p. 7484-5. https://smalp.net/index.html
  2. Carter J.G., et al., Proc Natl Acad Sci U S A. 2021 Aug 31;118(35) https://www.birmingham.ac.uk/news/latest/2021/08/birmingham-researchers-confirm-speed-simplicity-and-sensitivity-for-new-covid-19-test.aspx

BBSRC Strategic Research Priority: Renewable Resources and Clean Growth:Industrial Biotechnology

    Techniques that will be undertaken during the project:

    • Membrane protein expression, extraction and purification
    • Biophysics (including fluorescence, absorbance, circular dichroism, analytical ultracentrifugation, dynamic light scattering).
    • Imaging including electron and fluorescence microscopy
    • DNA chemistry and chemical conjugation
    • Polymer chemistry
    • Assay design and development

    Contact: Professor Tim Dafforn, University of Birmingham