Engineered Protein Nanoparticles for Targeted Modulation of Biomolecular Condensates in Cancer

ongoing

"Biomolecular condensates, formed by liquid-liquid phase separation (LLPS), play a pivotal role in diverse biological processes and diseases, including cancer. Despite their importance, it is still a challenge to understand the role of condensates in biological regulation. ""NanoProt4Cond"" aims at exploring the Wnt signalling pathway, deregulated in cancers like colorectal cancer, using the cutting-edge high-throughput technology ‘PhaseScan’ to investigate condensate formation by Wnt-related proteins. After identifying the proteins driving condensate formation, the project will engineer consensus-designed tandem repeat proteins (RPs) as condensate modulators (c-mods) by grafting short linear peptide motifs (SLiMs) from Wnt-pathway proteins onto RPs, creating multi-valent and multi-functional c-mods. While nanoparticles have been widely studied for overcoming traditional therapy limitations, their interaction with biomolecular condensates remains unexplored. ""NanoProt4Cond"" will fuse the most promising c-mods with proteins that self-assemble into nanoparticles, creating engineered protein nanoparticles that offer precise control over multifunctionality and valency. The c-mod protein nanoparticles (c-NPs) will be tuned to target and modulate condensates, unlocking novel therapeutic strategies for cancer treatment. This project will deepen the understanding of condensate formation within the Wnt pathway and contribute to novel cancer therapeutics. Hosted at the University of Cambridge, this MSCA PF will provide advanced technical training in protein design, molecular therapies, and biomolecular condensates, allowing the researcher to apply her expertise in nanomaterials and biomedicine while expanding her skills in supervision, project management, and proposal writing. "