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*EASTBIO* Optical based technologies to uncover the role of the protein. Willin/FRMD6, in mammalian neurodevelopment and neurodegeneration.


School of Biology

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Prof F Gunn-Moore , Prof K Dholakia No more applications being accepted Competition Funded PhD Project (Students Worldwide)

About the Project

How the mammalian system develops and works under normal physiological conditions is still not understood.Though many biochemical pathways have been identified to be involved in this process, maybe surprisingly, new ones are still being discovered. We have recently identified a new signal transduction pathway, that has normally been thought to have a role in the development of organs outside of the nervous system, but is now also involved in neuronal development, and potentially in neurdegeneration processes. Specifically, we identified a protein, Willin/FRMD6, which we first discovered as part of the Hippo signalling pathway (DOI: 10.1038/onc.2011.224), is able to influence the growth and development of neuronal cells. It appears to do this via activating specific biochemical pathways but also, and by utilising a novel optical based technology which can measure accurately the minute physical forces that cells make on their substrate, we have very recently shown that Willin/FRMD6 can also influence the biophysical properties of cells (DOI: 10.3389/fncel.2020.552213).

In this project, we wish to extend our studies into looking at the effects of Willin/FRMD6 on primary neuronal differentiation but also synaptic activity. To uncover the latter question, we will use another novel optical based technology which we have developed, where we can measure the connectivity of a neuronal network in a new high throughput optogenetics technique (DOI: 10.3389/fnins.2018.00451). We will also utilise our bespoke advanced optical microscopy that we have previously developed including novel light sheet and super-resolution microscopy. By utilising this blend of cutting-edge optical technology, we will be able to identify how Willin/FRMD6 can change neuronal development. More recently Willin/FRMD6 has also been shown potentially to be involved in neurodegeneration, as such our studies will under-pin the understanding of the fundamental mechanisms involved in these processes. As indicated above, the successful candidate will develop a wide range of highly sought-after interdisciplinary skills from culturing primary neuronal cells (including brain slice), through to biochemistry and advanced optical technologies.

Application procedure
In order to apply for this position, please follow the application instructions under http://www.eastscotbiodtp.ac.uk/how-apply-0 to obtain the EASTBIO Application form.

Then, submit the EASTBIO application form and your academic transcripts as part of a formal online application- https://www.st-andrews.ac.uk/study/apply/postgraduate/research/

In the online application form, you will be asked to provide contact details for two academic references. Please ask your referees to use the EASTBIO reference form provided under the link above when preparing their support letter, and to ensure references are provided by the deadline on 6 January 2021.

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership http://www.eastscotbiodtp.ac.uk/how-apply-0.

This opportunity is open to UK and International students and provides funding to cover stipend and UK level tuition. For international candidates, the University of St Andrews will cover the Home-International fee difference. Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.

References

Willin/FRMD6 expression activates the Hippo signaling pathway kinases in mammals and antagonizes oncogenic YAP.
Angus L, Moleirinho S, Herron L, Sinha A, Zhang X, Niestrata M, Dholakia K, Prystowsky MB, Harvey KF, Reynolds PA, Gunn-Moore FJ.
Oncogene. 2012 31(2):238-50.

All-Optical Assay to Study Biological Neural Networks.
Afshar Saber W, Gasparoli FM, Dirks MG, Gunn-Moore FJ, Antkowiak M.
Front Neurosci. 2018 12:451.

Willin/FRMD6 Influences Mechanical Phenotype and Neuronal Differentiation in Mammalian Cells by Regulating ERK1/2 Activity
Kronenberg N, Tilston-Lunel A, Thompson F, Chen D, Yu W, Dholakia K, Gather M, Gunn-Moore FJ
Front Cell Neurosci. 2020


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