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  BBSRC EASTBIO DTP: Determining the role of new molecules in activity-dependent bulk endocytosis


   College of Medicine and Veterinary Medicine

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  Prof M Cousin, Dr Karen Smillie  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

Synaptic vesicle (SV) endocytosis at the presynapse is essential for the maintenance of neurotransmission, particularly during intense neuronal activity. Under these conditions the dominant SV endocytosis mode is activity-dependent bulk endocytosis (ADBE), suggesting it should perform a central role in brain function. However determining the physiological role of ADBE in neurotransmission has been hindered by a limited understanding of its molecular mechanism. This project will address this challenge by discovering presynaptic molecules with a specific and selective role in ADBE. This will be achieved by exploiting the recently generated ADBE proteome – which has revealed a series of presynaptic molecules with no currently identified function. The role of these candidate molecules in ADBE and other endocytosis modes will be determined using a palette of live fluorescent imaging assays in primary neuronal cultures. Molecules that are specific to ADBE will to taken forward to determine their molecular mechanism using a series of biochemical interaction studies. In addition to this there is the opportunity to generate transgenic animals lacking specific molecules to determine their function in vivo. This project will therefore provide training in a series of state of the art technologies addressing a key biological problem.

Applications:
Completed application form along with your curriculum vitae should be sent to our PGR student team at [Email Address Removed]

References:
Please send the reference request form to two referees. Completed forms for University of Edinburgh College of Medicine and Veterinary Medicine project should be returned to [Email Address Removed] by the closing date: 5th December 2018.

It is your responsibility to ensure that references are provided by the specified deadline.

Download application and reference forms via:
https://www.ed.ac.uk/roslin/postgraduate/bbsrc-eastbio-dtp

Funding Notes

Eligibility:
All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. To qualify for full funding students must be UK or EU citizens who have been resident in the UK for 3 years prior to commencement.

References

Nicholson-Fish J.C., Kokotos, A.C., Gillingwater T.G., Smillie K.J.* and Cousin M.A.* (2015) VAMP4 is an essential cargo molecule for activity-dependent bulk endocytosis. Neuron 88: 973-984.
Smillie K.J., Pawson J, Perkins E.M., Jackson M. and Cousin M.A. (2013) Control of synaptic vesicle endocytosis by an extracellular signalling molecule. Nature Commun. 4: 2394.
Clayton E.L., Sue N., Smillie K.J., O’Leary T., Bache N., Cheung G., Cole, A.R., Wyllie D.J, Sutherland C., Robinson P.J. and Cousin M.A. (2010) Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles. Nature Neurosci. 13: 845-851.

Where will I study?