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Amplification Strategies for Mobile Phone-Based Assays for Vaccine Preventable Diseases


Project Description

The last 10 years have seen a number of breakthroughs in diagnostic technologies for protein biomarker detection in patient derived samples. Cutting-edge detection strategies are pushing for quantitative detection into the sub pg/mL sensitivity regime.1 Single binding event detection technologies capable of this hold great potential in disease progression monitoring and particularly, early disease detection. While the diagnostic landscape is rich with technologies that seek to meet these targets via a number of different platforms, a particular challenge is realising methods capable of sub-pg/mL sensitivity in a “REASSURED” way.2 Developing technologies that can be used simply and with a minimal financial burden opens up new opportunities in how diagnostic screening approaches can be employed in resource limited settings. This is particularly true for diagnostics technologies to enable vaccine preventable disease surveillance to help inform vaccine manufacture and distribution.

This PhD project will focus on the bridging of advanced hard and soft nanotechnology concepts to engineer new approaches towards REASSURED diagnostics. The coupling of nano- and micro-particle signalling structures with synthetic biology apparatus will be explored to amplify the signal of single-molecule binding events and enable digital detection by a mobile phone camera. These studies will be performed to realise detection systems amenable to automated detection through the use of the mobile phones onboard computer which can be further explored to reduce the impact of non-specific signal and provide a route towards effective connectivity of results.3

The PhD will be located within the Thomas and Frank Labs in the London Centre for Nanotechnology and the Department of Biochemical Engineering respectively, at University College London. The Thomas lab is a collaborative and multidisciplinary group focussing on the development of affordable, computationally enhanced nanomaterial systems to democratise the future generation of diagnostic technologies with close ties to the i-sense EPSRC IRC consortium and the Future Vaccine Manufacturing Research Hub.4 The Thomas lab will train the candidate in nanoparticle synthesis, modification and characterisation as well as the design and testing of diagnostic systems using mobile phone technologies for their analysis. The Frank Lab is a collaborative synthetic biology lab focused on engineering genetically programmable protein nanomaterials for applications in cancer immunotherapy, drug-delivery, vaccine development and diagnostics.5-7 The Frank lab will train the candidate in molecular and microbiology methodologies, synthetic circuit design, bioinformatics, protein expression and particle analysis using biochemical and biophysical techniques.

Applicants would be expected to have a good 2.1 degree or above in Engineering or Physical Sciences, preferably with demonstrable experience in Biological Sciences or Chemistry. The project will be highly multidisciplinary incorporating elements from nanotechnology, materials engineering, chemistry and synthetic biology. A successful candidate should be able to demonstrate an aptitude for analytical sciences and any experience in programming would be desirable.

The starting date for this PhD will be February 2020. To apply for this studentship, please send your two-page CV and cover letter by email to Ms Andrea Kezer, CDT Manager & Postgraduate Programmes Manager () to arrive no later than 12pm on Friday, 10th January 2020. For queries related to this position, please contact Dr Michael Thomas (Supervisor: ) and Dr. Stefanie Frank (Secondary Supervisor: ).

Funding Notes

This research project has funding attached. It is only available to UK citizens or those EU citizens who have been resident in the UK for a period of 3 years or more (restrictions apply). The studentship covers the full cost of UK/EU tuition fees, plus a tax free stipend of £17,009 p.a. for four years. See EPSRC website for eligibility: View Website

References

1. Loynachan, C.N., Thomas, M.R., Gray, E.R., Richards, D.A., Kim, J., Miller, B.S., Brookes, J.C., Agarwal, S., Chudasama, V., McKendry, R.A., Stevens, M.M., Platinum Nanocatalyst Amplification: Redefining the Gold Standard for Lateral Flow Immunoassays with Ultra-Broad Dynamic Range. ACS Nano, 12(1), 279 (2017) doi:10.1021/acsnano.7b06229
2. Land, K.J., Boeras, D.I., Chen, X-S., Ramsay, A.R., & Peeling, R.W., REASSURED diagnostics to inform disease control strategies, strengthen health systems and improve patient outcomes. Nat Microbiol 4, 46–54 (2019) doi:10.1038/s41564-018-0295-3
3. Wood, C.S., Thomas, M.R., Budd, J., Mashamba-Thompson, T.P., Herbst, K., Pillay, D., Peeling, R.W., Johnson, A.M., McKendry, R.A., & Stevens, M.M., Taking connected mobile-health diagnostics of infectious diseases to the field. Nature 566, 467–474 (2019) doi:10.1038/s41586-019-0956-2
4. https://www.i-sense.org.uk , https://www.ucl.ac.uk/biochemical-engineering/research/research-and-training-centres/vax-hub
5. https://2019.igem.org/Team:UCL (Dr Stefanie Frank team leader)
6. Lee, M.J., Mantell, J., Brown, I.R., Fletcher, J.M., Verkade, P., Pickersgill, R.W., Woolfson, D.N., Frank, S. and Warren, M.J., De novo targeting to the cytoplasmic and luminal side of bacterial microcompartments. Nature communications, 9(1), p.3413. (2018) doi:10.1038/s41467-018-05922-x
7. Lee, M.J., Mantell, J., Hodgson, L., Alibhai, D., Fletcher, J.M., Brown, I.R., Frank, S., Xue, W.F., Verkade, P., Woolfson, D.N. and Warren, M.J., 2018. Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm. Nature chemical biology, 14(2), p.142. (2018) doi.org/10.1038/nchembio.2535

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