Ubiquigent Limited, a drug discovery and development company harnessing novel deubiquitinase (DUB) modulators as new therapeutics for areas of high unmet medical need, is supporting a Master’s student at the University of Glasgow (UoG) to undertake a research project on USP30, a DUB implicated in neruodegenerative, renal, and cardiovascular diseases.
Overseen by structural biology experts Helen Walden, UoG, and Mehmet Gundogdu, principal scientist at Ubiquigent, the project aims to combine biochemistry, in vitro complex protein assembly and protein crystallography to interrogate the mechanism underlying USP30 inhibition by selected proprietary compounds. As well as promoting fundamental research on this strategic enzyme, the project will assist Ubiquigent’s USP30 program. The studentship is fully funded by Ubiquigent.
USP30 regulates the clearance of damaged mitochondria in a process called mitophagy. Dysregulation of mitophagy is closely linked to the development of several diseases, with USP30 modulation offering a potential treatment; USP30 inhibition, for example, has been proposed as a therapeutic strategy for Parkinson’s disease (PD). Although numerous USP30-targeting compounds are reported in scientific literature, only one has been approved to enter clinical evaluation so far, and the design and discovery of new compounds is hampered by a lack of a suitable USP30 crystal structure in the public domain.
The project aims to overcome this barrier, bringing together the expertise of both groups to deliver a bespoke USP30 structural biology platform to identify novel inhibitors for treatment of a range of diseases including PD.
Helen Walden, professor of Structural Biology, Head of School (Molecular Biosciences), University of Glasgow, said: “There is huge potential to exploit USP30 as a therapeutic target across many indications, including cardiovascular, renal, and neurodegenerative diseases. My team has worked extensively on resolving the structures of both DUBs and E3 ligases, and I look forward to combining this experience with Ubiquigent’s drug discovery expertise to support the Master’s student and resolve the crystal structure of USP30 for the design of novel therapeutics.”
Mehmet Gundogdu, principal scientist, Ubiquigent, added: “Collaborating with Professor Walden on this project is an exciting opportunity to combine forces in an important therapeutic area. USP30 is a prominent target in the DUB drug discovery space, and this project has great potential to enable the structure-led design and development of novel USP30 modulators.”
Sheelagh Frame, chief scientific officer, Ubiquigent, concluded: “We are delighted to support the Master’s student, Niyati Gupta Kheskani, in Professor Walden’s laboratory. By determining the structure of USP30 in complex with proprietary inhibitor compounds, our joint objective is to further enable USP30-focused drug discovery and move one step closer to the clinic. This is a great opportunity to support the development of the next generation of scientists, as well as to strengthen our relationship with Professor Walden and her team.”