Do multi-proteinopathies differ in their molecular pathology from processes involving deposition of single proteins?

During pathogenesis of protein misfolding diseases there is often deposition of multiple proteins, not just the protein that is characteristic of the disease in question. This is exemplified by Alzheimer’s disease, which involves aggregation of Aβ, tau and often α-synuclein, amongst others. The involvement of multiple types of protein aggregate may be a key driver of bona fide disease, since many transgenic mouse models of disease replicate accumulation of individual proteins without many of the other pathogenic signs of disease. We have identified two different diseases in animals showing deposition of multiple proteins, including phosphorylated tau, which allows us to study the molecular mechanisms that may underpin the involvement of multiple types of protein deposits. One disease is based upon experimental prion disease in mice whilst the other is a naturally-occurring disorder of aged cattle. We will use proteomic methodologies to determine molecular differences between tissues that are from simple- or more complex-proteinopathies with a view to determining biochemical networks that are causative for multi-proteinopathies. We expect that these pathways are key to the other pathogenic events in neurodegenerative disorders and our data will potentially allow these pathways to be targeted pharmacologically to potentiate these deadly diseases.

Overall, the proposals contain a range of molecular and pathological studies that we expect will shed light on the mechanisms of multi-proteinopathies. As well as experiments that will clearly generate cutting edge, international quality data, there are several areas where follow up studies can be performed, depending on the data that is generated, most notably the proteomics work that could spur fruitful follow on areas of research. Within Edinburgh, the community of researchers and clinicians studying neurodegenerative disease (and neuroscience in general) is large and world-leading and this provides an environment that will ensure success for the studies.

Funding: This project is eligible for a University of Edinburgh 3year PhD studentship or Principal’s Career Development Studentship. ( http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/uk-eu/university-scholarships/development)

International students should also apply for an Edinburgh Global Research Studentship (http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/international/global/research).


Application Procedure:
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be sent to: Liz Archibald, The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG or emailed to [Email Address Removed].

When applying for the studentship please state clearly the title of the studentship and the supervisor/s in your covering letter.

All applicants should also apply through the University’s on-line application system for September 2017 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=832

Applicants for the Principal’s career development studentship must also complete the specific on-line application form at http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/uk-eu/university-scholarships/development