Polyglutamine expansion in aggregation AR in cells
Summary - $91,350. (two-year award) $49,350 (2023) and $42,000 (2024). Polyglutamine expansion in aggregation AR in cells: The Salvatella laboratory in IRB Barcelona has recently shown that the androgen receptor works by forming nuclear clusters called transcriptional condensates. AR condensation can be beneficial because it facilitates gene expression; however, it can also accelerate protein aggregation, a process in which protein molecules lose their activity by forming insoluble clumps that are harmful to cells. With the support of the KDA the team will investigate whether the polyglutamine expansion associated with Kennedy’s disease causes transcriptional condensates to become dysfunctional due to androgen receptor aggregation. In addition, it will test whether drug-like molecules can accumulate in the transcriptional condensates formed by the mutated receptor and prevent its aggregation. The work will increase our understanding of the molecular basis of the disease and allow us to explore a new therapeutic avenue for Kennedy’s disease.
Bio: Xavier Salvatella studied chemistry at the University of Barcelona (BSc) and Queen Mary College, London (MSc). He completed his PhD at the University of Barcelona, where he studied the interaction between synthetic molecules and hydrophilic surfaces in proteins such as the tumour suppressor P53. He conducted postdoctoral work at the University of Cambridge, combining experiments and simulations to investigate the structural heterogeneity of intrinsically disordered, partially folded and globular proteins. He leads the laboratory of molecular biophysics at IRB Barcelona, where he studies the involvement of intrinsically disordered domains in disease and how to inhibit their functions with drug-like small molecules. Recently, he co-founded the company Nuage Therapeutics, which develops drugs targeting intrinsically disordered targets for oncolog
