How do fat cells cause muscle wasting in cancer?

This project is one of 16 four year PhD Studentships funded by Medical Research Scotland (https://www.medicalresearchscotland.org.uk) to be delivered jointly by the named University and External Partner Organisation (EPO). The Studentship will provide the first-class academic and additional training provided by the EPO needed to equip the successful candidate for a science career in an increasingly competitive market.

"Probing the biology of Zinc alpha-2 glycoprotein" to be delivered by the University of Strathclyde [Supervisors: Professor Gwyn W Gould and Dr Margarent R. Cunningham (Strathclyde Institute of Pharmacy & Biomedical Sciences)] and Moleculomics Ltd (https://moleculomics.com/) [Company supervisor: Dr Jonathan Mullins].

Cachexia is characterised by depletion of adipose and skeletal muscle tissue. It is a major debilitating effect of some tumours, implies poor prognosis and accounts for 20% of cancer deaths. A characteristic feature of cachexia is the loss of body fat.

Zinc alpha-2-glycoprotein (ZAG) appears to be a powerful mediator of this loss of fat. ZAG is produced and secreted from adipocytes. ZAG is also implicated in obesity and Type-2 diabetes and present data suggests that ZAG plays a protective role in maintaining appropriate fat mass and insulin sensitivity.

These studies indicate that controlling ZAG’s activity could be life-saving in the management of certain cancers and other cachexia-inducing conditions. Moreover, the role of ZAG in body fat store homeostasis is deserving of understanding in its own right. The potential to identify small molecules that might modulate ZAG function offers significant potential in both cancer and diabetes research, areas of primary importance to the health of Scotland.

Our project comprises inter-related elements. The student will first optimise expression/purification of ZAG before embarking on a suite of studies examining signalling and gene expression changes driven by ZAG. The effects of small molecule mimetics on selected aspects of ZAG function will then be tested.
i. To characterise the molecular basis of ZAG signalling;
ii. To determine the effects of recombinant ZAG on adipocyte biology;
iii. To identify small molecule mimetics that can bind to the MHC-site on ZAG;
iv. To characterise the biological consequence of these small molecule mimetics.

ENQUIRIES:
Enquiries should be sent by email to Professor Gwyn W Gould:
[Email Address Removed]

APPLICATIONS:
Applicants must have obtained, or expect to obtain, a first or 2.1 UK honours degree, or equivalent for degrees obtained outside the UK, in biochemistry, cell biology or a related biological sciences subject.

Applicants should send a CV, the contact details of 2 references (including email addresses) and a covering letter, explaining why the applicant wishes to carry out this project, by email to Professor Gwyn W Gould:
[Email Address Removed]

Please note, your application may be shared with the funders of this PhD Studentship, Medical Research Scotland andMoleculomics Ltd.

Interviews are expected to take place 3-4 weeks after the closing date for applications. In light of the current coronavirus situation, interviews may be conducted by video conference.

It is anticipated that the PhD Studentship will start in October 2020.