PhD Studentship: Development of LA1011 for high affinity binding to Hsp90 for use towards healthy ageing in patients showing Alzheimer’s symptoms

PhD Studentship

Biochemistry

University of Sussex

Funding for: UK Students

Funding amount: Home (UK) tuition fees and stipend at standard UKRI rates.

A PhD studentship (4 years) is available from September 2024 under the supervision of Dr. Chrisostomos Prodromou, Biochemistry and Biomedicine department, School of Life Sciences.

Deadline: 5th May 2024

PROJECT TITLE: Development of LA1011 for high affinity binding to Hsp90 for use towards healthy ageing in patients showing Alzheimer’s symptoms.

BRIEF DESCRIPTION OF THE PROJECT: With 50 million global cases of Alzheimer’s disease (AD) and care costs of 1 trillion UK pounds (expected to triple by 2050), there is a pressing need to slow disease progression, sustain productive lives and reduce costs. We have shown that LA1011 eliminates neurodegeneration in an AD mouse model and identified the Hsp90-FKBP51 complex as the molecular target.

There are three project aims:  A). A structure-based design of LA1011 to improve Hsp90 binding. B). Using biochemical, biophysical and cellular approaches, we will evaluate the importance of FKBP51 and other cochaperones (Aha1, FKBP52 etc) involved in the phosphorylation of Tau, which also compete with LA1011 for Hsp90 binding. C). LipidArt (our industrial partner) are uniquely placed to investigate whether LA1011 alters the membrane physical state, organization and effects on the lipidom and cause the co-induction effect of LA1011. This is a very relevant question since FKBP51 is involved in adipogenesis and lipid metabolism.

There is potential that full AD onset could be prevented by developing LA1011. LA1011 may be applicable to other chaperone dependant neurodegenerative diseases. LA1011 is a useful reagent for use to better understand the complex nature of the Hsp90 mechanism per se, but also in the context of a variety of other diseases (from inflammation to cancer). The project offers an excellent multidisciplinary training opportunity.

A strong interest in protein science and drug development would be favourable.

Informal enquiries about the project can be made to Chrisostomos Prodromou at [email protected] .

Funding:

University of Sussex is a member of the SoCoBio Doctoral Training Partnership, funded by the Biotechnology and Biosciences Research Council (BBSRC). Successful applicants follow a four-year research skills training programme and will have their UK PhD tuition fees and living allowance (£19,237 for 2024-25) covered for the four years. They will also have access to further funds for research expenses. They will benefit from a placement, taught modules in entrepreneurship and data management and from Socobio summer schools and conferences.

How to apply:

Please submit a formal application using the online admissions portal attaching a CV, degree transcripts and certificates, personal statement, and two academic referees. A research proposal is not required.

On the application system select Programme of Study – PhD Biochemistry. Please state the project title under funding obtained and the supervisor’s name where required.

Candidates should have or expect to obtain a minimum 2:1 undergraduate degree. An MSc degree will be advantageous. Your qualification should be in Biochemistry or a related subject area. You may also be considered for the position if you have other professional qualifications or experience of equivalent standing.

Applications are particularly welcomed from candidates with protected characteristics – e.g., from Black and other ethnic minorities – who are under-represented in postgraduate research at our institution.

For enquiries about the application process, please email Emma Chorley: [email protected]