Jing-Ke Weng

Sponsor: The Chan Zuckerberg Initiative

A Plant Small-Molecule Discovery Platform to Study Neurodegeneration (CP2-Weng) 

The proposed research aims to develop a plant-based drug screening platform to identify small molecules that can disrupt protein and RNA aggregation associated with neurodegenerative diseases such as Huntington’s, Alzheimer’s, and Parkinson’s. The project will utilize the unique lyciumin peptide biosynthesis pathway in plants to generate a diverse library of cyclic peptides. These peptides will be screened in engineered tobacco BY-2 cells expressing aggregation-prone proteins (e.g., huntingtin) and RNAs (e.g., CAG repeats) to identify compounds that alleviate cellular toxicity and alter aggregation kinetics. Lead compounds will be further evaluated in mammalian cell models to assess their efficacy and mechanism of action. The established screening platform and identified compounds will be made available to the research community, potentially offering new tools and therapeutic strategies for studying and treating neurodegenerative disorders.