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MRC DiMeN Doctoral Training Partnership: The molecular assembly of perineuronal nets by super-resolution microscopy in ageing brains


   MRC DiMeN Doctoral Training Partnership

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  Dr J. Kwok, Dr Izzy Jayasinghe, Dr R Richter  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Does biochemistry affect biomechanics? How would the interplay of these two factors affect neuroplasticity, particularly in neurodegeneration and spinal cord injury? Here is a PhD project which may answer these questions.

Perineuronal nets (PNNs) are specialised extracellular matrix structures that ensheath selected neurons in the brain. They are assembled from four types of extracellular matrix molecules: the polysaccharide hyaluronan (HA), link proteins, chondroitin sulphate proteoglycans (CSPGs) and tenascin-R (Tn-R). It is now widely accepted that PNNs are involved in regulating synaptic plasticity. PNN modulation provides a promising avenue for plasticity enhancement in diseases, including Alzheimer’s disease and spinal cord injury. It is essential to elucidate the spatial relationship of PNN molecules and synapses, thus providing an in depth understanding of how synaptic plasticity could be controlled.

In this project, you will interrogate the spatial organisation and dynamics of molecules in the PNNs, and how PNNs interact with neighbouring synapses in situ. The student will apply state-of-the-art imaging techniques including super-resolution expansion microscopy (ExM, second supervisor), in combination with biophysical and dynamic analyses of PNN molecular assembly (third supervisor) to investigate the dynamics of PNNs on neuronal surfaces (primary supervisor). The results will provide essential insights on the molecular mechanisms underpinning PNN-mediated neuronal plasticity and facilitate drug design for PNN modulations.

Please contact us if you have any question. More information can be found in:

https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/99/dr-jessica-cf-kwok

https://www.sheffield.ac.uk/biosciences/people/mbb-staff/academic/izzy-jayasinghe

https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/129/dr-ralf-richter

Alternatively, you can learn about our research focus in the Twitters pages: @KwokLab, @i_jayas and @LabRichter.

Benefits of being in the DiMeN DTP:

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, York 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: https://www.dimen.org.uk/blog

Further information on the programme and how to apply can be found on our website: https://www.dimen.org.uk/how-to-apply


Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 4yrs. Funding will cover tuition fees, stipend and project costs. We also aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of full studentships to international applicants. Please read additional guidance here: https://www.dimen.org.uk/eligibility-criteria
Studentships commence: 1st October 2023
Good luck!

References

1) Yang S et al. (2021) Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Mol Psychiatry.
DOI: 10.1038/s41380-021-01208-9
2) Sheard TMD et al. (2019) Three-Dimensional and Chemical Mapping of Intracellular Signaling Nanodomains in Health and Disease with Enhanced Expansion Microscopy. ACS Nano.
DOI: 10.1021/acsnano.8b08742
3) Richter RP et al. (2018) Glycosaminoglycans in extracellular matrix organisation: are concepts from soft matter physics key to understanding the formation of perineuronal nets? Curr Opin Struct Biol 50:65-74.
DOI: 10.1016/j.sbi.2017.12.002
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