Targeting Transglutaminase-2 -heparan sulfate interaction in kidney fibrosis

Fibrotic remodelling in Chronic Kidney Disease (CKD) is an unmet clinical need, with increasing social-economic costs, being linked to aging and type-2 diabetes. The extracellular matrix (ECM) crosslinking enzyme transglutaminase-2 (TG2) is highly implicated in fibrosis progression which precedes end-stage kidney failure, hence it is a potential therapeutic target. Modulation of TG2 significantly affects kidney scarring, and targeted TG2-deletion leads to decreased kidney fibrosis in experimental models of CKD. Recent studies have highlighted a novel interaction of TG2 with heparan sulphate (HS)-proteoglycans, and suggested that this interaction may be important for controlling the cell-surface trafficking and activity of TG2 in the ECM [1-3]. Furthermore, the Verderio Edwards’ group has mapped the heparin/HS-binding site(s) on TG2 [4]. Despite several advances, more research is needed before the TG2-HS interaction can be exploited in CKD-therapy. Using a number of biochemical approaches, from expression and purification of recombinant proteins, to SPR and FRET microscopy, the project aims to test the hypothesis that HS is a key modulator of the cross-linking activity of TG2.

The proposed research builds on previous work on TG2 in CKD, for which the Verderio Edwards’ team at NTU have gained international recognition. This is a multidisciplinary projects supported by a supervisory team with complementary specialistic expertise. Seen the detrimental effect of uncontrolled cross-linking on fibrosis progression, the project has the potential to impact outside academia. The successful candidate will be expected to engage in research as part of a thriving team at NTU in a dynamic international environment. The post will offer opportunities to travel, present at conferences and connect with pharmaceutical industry.

Specific qualifications/subject areas required of the applicants for this project:
Applicants should hold, or be expected to hold, an UK Master’s degree (or UK equivalent according to NARIC) with a minimum of a commendation, and/or a UK 1stClass / 2.1 Bachelor’s Honours degree (or UK equivalent according to NARIC) in Biochemistry, Biotechnology, Cell Biology, Pharmacology, Biology, Biomedical Sciences or a related discipline. A Biochemistry background and interest in biotechnologies is desirable.

Panel members who will perform shortlisting:
Chair: Prof Ellen Billett [Email Address Removed]
Panel member 1: Dr Elisabetta Verderio Edwards, [Email Address Removed]

Panel member 2: Dr Quentin Hanley or Prof Carole Perry (or both)

Interviews are likely to take place on the following dates: 08/01/2018 to 19/01/2018

This studentship competition is open to applicants who wish to study for a PhD on a full-time basis only. The studentship will pay UK/EU fees (currently set at £4,195 for 2017/18 and are revised annually) and provide a maintenance stipend linked to the RCUK rate (this is revised annually and is currently set at £14,553 for the academic year 2017/18) for up to three years. Applications from non-EU students are welcome, but a successful non-EU candidate would be responsible for paying the difference between non-EU and UK/EU fees. (Fees for 2017/18 are £12,900 for non-EU students and £4,195 for UK/EU students). The studentships will be expected to commence in October 2018.