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MRC DiMeN Doctoral Training Partnership: Synthesis, characterisation and medical applications of photoluminescent biocompatible gold nanoclusters


MRC DiMeN Doctoral Training Partnership

Newcastle United Kingdom Biochemistry Biophysics Biotechnology Medical Physics Molecular Biology Structural Biology Synthetic Chemistry

About the Project

There is increasing demand for novel materials with healthcare applications. A group of compounds with great potential in this area are gold nanoclusters. These are particularly attractive for diagnostic imaging and phototherapy due to their photoluminescence, photostability and biocompatibility. The properties of gold nanoclusters depend on the number of gold atoms they contain, and methods are being devised to enable this to be more carefully controlled. An emerging approach with great potential, uses proteins as scaffolds to template gold nanoclusters synthesis. 

A novel family of bacterial copper storage proteins (the Csps) are four-helix bundles whose cores are lined with Cys residues, excellent ligands for gold. This makes them ideal as biotemplates for developing the field of protein-stabilised gold nanoclusters. The Dennison group (Newcastle University) discovered the Csps (Nature 2015, 525, 140-143) and has extensive experience in studying these proteins. Csps will be used to synthesise protein-stabilised gold nanoclusters. Characterisation will involve an array of approaches available across the supervisory team, including UV-visible, fluorescence and circular dichroism spectroscopies. How gold is bound within a range of Csps, including site-directed mutants, will be investigated by crystallising complexes to enable structure determination with the Pohl group (Durham University). The entry of Csp-gold nanocluster complexes into human cells will be investigated using confocal fluorescence microscopy. Understanding the effect of structure on cellular behaviour is key for medical applications of protein-bound gold nanoclusters.

A highly complementary supervisory team, also involving Prof. Jeremy Lakey (Newcastle University) and an industrial partner (Nanoco Technologies Ltd), will ensure rapid progress. Cross-disciplinary training will be provided, including in molecular and synthetic biology, biochemistry, biophysics, structural biology, bionanotechnology, cell-culture and bioimaging, as well as working in an industrial setting. The student will learn how to produce publication-quality data by contributing to manuscripts describing their work, resulting in co-authorship of research articles.

Potential applicants are strongly encouraged to contact the lead supervisor  for further details prior to submitting an application.

Information about the research groups can be found at:

https://www.ncl.ac.uk/medical-sciences/people/profile/christopherdennison.html

https://www.dur.ac.uk/research/directory/staff/?id=5500

https://www.ncl.ac.uk/cbcb/staff/profile/jeremylakey.html#background

https://www.nanocotechnologies.com/

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards

Further information on the programme and how to apply can be found on our website:

https://bit.ly/3lQXR8A 


Funding Notes

Funded by the MRC for 3.5yrs, including a minimum of 3 months working within the industry partner.

Funding will cover UK tuition fees and an enhanced stipend (around £17,785) only. We aim to support the most outstanding applicants from outside the UK. We are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme. Please read additional guidance here: View Website
Studentships commence: 1st October 2021.
Good luck!

References

N. Vita, S. Platsaki, A. Baslé, S. J. Allen, N. G. Paterson, A. T. Crombie, J. C. Murrell, K. J. Waldron and C. Dennison, A four-helix bundle stores copper for methane oxidation. Nature 2015, 525, 140-143.
T. Robson, D. S. H. Shah, A. S. Solovyova and J. H. Lakey, Modular protein engineering approach to the functionalization of gold nanoparticles for use in clinical diagnostics. ACS Appl. Nano Mater. 2018, 1, 3590-3599.
D. R. Chisholm, C. W. E. Tomlinson, G. L. Zhou, C. Holden, V. Affleck, R. Lamb, K. Newling, P. Ashton, R. Valentine, C. Redfern, J. Erostyák, G. Makkai, C. A. Ambler, A. Whiting and E. Pohl, Fluorescent retinoic acid analogues as probes for biochemical and intracellular characterization of retinoid signaling pathways. ACS Chem. Biol. 2019, 14, 369-377.

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