Mobile Phone-Based Disease Detection: Towards Single-Molecule Approaches: Sept/Oct 2020 Start

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 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 cheap, robust and accessible 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 PhD project will focus on the bridging of advanced hard and soft nanotechnology concepts to engineer new approaches towards diagnostics for resource limited settings. The coupling of nano- and micro-particle signalling structures with components made possible by synthetic biology techniques will be explored to amplify the signal of detection events towards enabling single-molecule binding event detection by a mobile phone camera.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, nanomaterial enhanced systems for ultrasensitive disease detection with a priority of democratising 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, characterisation, diagnostic design and testing. 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 synthetic biology and working with nanomaterials. 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.

Interested candidates should submit a formal application through UCL’s Application portal to the Research Degree: Biochemical Engineering programme [RRDBENSING01], noting in the statement section that they are applying for this particular project. Applicants should also send their CV and covering letter to Dr Michael Thomas (), outlining your interest in and suitability for, researching the suggested topic.

Applications will be accepted until 29th May 2020 but the position will be filled as soon as a suitable candidate has been identified. The project will commence in September/October 2020. Any inquiries for further information about the studentship should be emailed to .

Funding Notes

The project is funded through EPSRC Doctoral Training Partnership (DTP). The studentship will cover the successful candidate’s Home/EU level fees and provide an annual stipend in line with UCL’s studentship budget figures.

Applicants must meet the EPSRC eligibility conditions to be eligible for the award – in summary this typically means that applicants must have no restrictions on their right to live in the UK permanently and have been resident in the UK for three years immediately prior to the studentship commencing. Please see EPSRC’s website for further details: 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