“Characterisation of stem cell derived microvesicles that promote the clearance of neuronal aggregates in ageing animals”

Supervisors: Professor Ketan Patel (University of Reading), Dr Dionne Tenatta (University of Oxford) and Dr Steve Ray (Natural Biosciences Ltd).

This project aims to identify the molecules present in adipose derived mesenchymal stem cell (ADMC) microvesicles that promote the clearance of protein aggregates which develop in the brain during ageing. This aim will be realised by forging an alliance between academia (University of Reading, University of Oxford) and industry (Natural Biosciences Ltd) to exploit a novel finding made by these partners. The student will spend time working with all three partner institutions.

Cell-cell communication is an essential feature for all normal physiological processes and during the development and response to pathophysiological conditions. A large number of studies have focused on identifying secreted factors that mediate cell-cell communication. However it is now apparent that the deployment of freely secreted molecules as a means of communication is likely to be an exception rather than the rule. Instead it is now held that biologically active molecules are usually present in a complex association with other entities. Microvesicles are emerging as potent mediators of cell-cell communication. Microvesicles are small membrane enclosed vesicles that are shed by a variety of cell types. Microvesicles are a heterogeneous population of particles that can fractioned into two major subpopulations based on their size (micro and nanoparticles). Their function depends not only on their size but also on the cargo that they carry and recent studies have shown that microvesicles can contain a variety of bioactive molecules including microRNA, mRNA, lipids, growth factors and other proteins. Once shed, microvesicles can enable the horizontal transfer of bioactive molecules to cells at distant sites.

We have been studying the development of protein aggregates in the ageing process to explain compromised tissue function in the elderly. Several recent studies have shown that stem cell produce factors that lead to the clearance of brain protein aggregates leading to a restoration of tissue function. We have recently found that microvesicles derived from ADMCs are as efficacious in restoring brain function as the cells themselves. We have developed the hypothesis that microvesicles derived from ADMCs contain factors that are capable of stimulating the clearance of protein aggregates thereby reversing age-related tissue abnormalities. This hypothesis will be tested by the student.

ELIGIBILITY: Applicants should hold a minimum of a 2:1 Honours Degree in a relevant subject.

FUNDING: This 4-year BBSRC CASE PhD Studentship covers UK/EU Fees and a Research Council stipend, commencing October 2013. Due to funding restrictions this Studentship is only open to UK/EU applicants. EU applicants must have resided full-time in the UK for the 3 years prior to the start of this Studentship.

HOW TO APPLY:  Candidates are requested to e-mail a one-page Cover Letter and CV, to Professor Ketan Patel: ketan.patel@reading.ac.uk. Please quote studentship reference GS13-27 in all correspondence.

CLOSING DATE: FRIDAY 29th MARCH 2013.