Medicinal chemistry will be used to develop screening hits into specific TRIM inhibitors that will be further validated in collaboration with TRIM-NET labs. We look for a candidate with a background in organic synthesis/ medicinal chemistry.

We will develop TRIM assays that will be used in high throughput small molecule screening campaigns to develop TRIM inhibitors in collaboration with ESR12. Prior experience with protein expression and purification/ structural biology is desired.

One of the specific requirements for an E3 ligase is the interaction with the ubiquitin-charged E2. The important role of E2 enzymes in determining ubiquitin chain length and topology, hence the final fate of the modified substrates, is nowadays well accepted.

The objective of this project is to understand E3-E2 pair selection and its determinants for the TRIM proteins studied within this network (TRIM8, 17, 19, 25, 28, 32, 33, 41, 63 and Malin). The ultimate goal is to explore novel strategies of drug design and screening to interfere with specific E3 activities.

Arsenic is used therapeutically to treat Acute Promyelocytic Leukaemia by inducing SUMO- dependent, ubiquitin-mediated degradation of the PML- RAR oncoprotein. The objective of the work will be to define the mechanism by which arsenic induces SUMO modification of PML (TRIM19) and will involve a combination of biochemical, proteomic and structural biology approaches.

Reduced E3 ubiquitin ligase activity of TRIM8 contributes to the glioma pathogenesis.
This study aims to identify TRIM8-partners and TRIM8 glioma-related functions. Transcriptomic, proteomic, and bioinformatics will be exploited to identify TRIM8- related glioma signatures, identify novel pathways that correlate with the pathophysiology of this tumour, and ultimately indicate therapeutic avenues

We previously identified TRIM28 as a direct interactor of the Androgen Receptor in prostate cancer cells, critically involved in prostate cancer cell proliferation. This study will: 1. identify the functional contribution of TRIM28 on Androgen Receptor function in prostate cancer cells, 2. Unravel the underlying basis of the observed genomic selectivity, 3. Reveal the clinical implications of TRIM28 on prostate cancer patient outcome and response to therapy, and 4. Expose how this TRIM28/AR interaction could be therapeutically exploited in the treatment of prostate cancer patients.