Descripció del projecte
Intrinsically disordered proteins (IDPs) are implicated in a variety of human pathologies, such as neurodegenerative disorders and cancer. Targeting IDPs with small molecules is however challenging due to their lack of a well-defined structure. IDPs are known to assemble into biomolecular condensates like stress granules and nucleoli, which have specific molecular compositions and physicochemical properties. Understanding the molecular properties that drive the selective partitioning of specific IDPs or molecules to specific biomolecular condensates is now a major focus of interest.
Selectively manipulating the properties of biomolecular condensates formed by IDPs with small molecules is a very attractive approach to target this challenging class of proteins. Nuage Therapeutics (NTx), a spin-off of ICREA and the Institute for Research in Biomedicine (IRB), is very interested in exploiting this selectivity for drug discovery, and the laboratory of molecular biophysics at the IRB is very interested in understanding the biophysical basis for selectivity.
The “Industrial PhD” that NTx and IRB propose will study the molecular basis for selectivity of drugs targeting IDPs in biomolecular condensates. The project will require the use of biophysical techniques, NMR, in vitro reconstitution experiments with purified proteins, molecular simulations and experiments in established cellular models. Experiments will be carried out at the IRB and, eventually, at the laboratory of NTx.
NTx will contribute to the project with protein targets (identified in house or licensed in), as well as compounds that selectively partition in biomolecular condensates (identified by NTx’s proprietary screening assay). The IRB will contribute its expertise in experimental and computational biophysics. All together will set strong basis for the success of the project.
