Faculty

Silvia Cavagnero
Silvia Cavagnero
Professor
1101 University Ave room 5357
(608) 262-5430
The Cavagnero group focuses on developing new spectroscopic techniques to study the structure/dynamics of biomolecules at high resolution and the fundamental principles of protein folding and misfolding in the cell. We focus on exploring the folding and misfolding of nascent proteins emerging from the molecular machine responsible for their biosynthesis, the ribosome. We also study how molecular chaperones affect protein folding. We employ both wet-lab techniques (biochemistry, bioconjugation, microbiology), spectroscopy (including single-molecule methods) and computation (folded and prion status predictions and kinetic simulations). Our work has several practical implications. First, the large-scale production of soluble proteins relevant to biotechnology and medicine, including protein-based drugs, will be enhanced by exploiting the principles we learn from the study of protein folding in the cell. Second, a better understanding of the role of the Hsp70 molecular chaperone in client-protein binding is leading us to rationally design novel antimicrobial agents targeting the protein folding machinery. Third, the mechanistic principles we are learning, focusing on the balance between protein folding and aggregation in the cell, feed useful principles for the control of deleterious aggregation processes leading to a variety of diseases, including prion-related disorders, Parkinson’s disease, Alzheimer's disease, Huntington's chorea and cancer. We are also developing novel laser-assisted methodologies to enhance the power NMR spectroscopy for the analysis of protein folding. Our efforts include laser- enhanced approaches to boost NMR sensitivity, new radio-frequency pulse schemes to overcome undesired NMR resonance line-broadening due to conformational exchange in the intermediate chemical shift timescale, and methods to site-specifically study the role of water in protein folding. Exciting new developments include laser-driven techniques based on photochemically-enhanced dynamic nuclear polarization (photo-CIDNP) and its application to heteronuclear correlation NMR in 15N and 13C isotopically enriched samples.
Affiliated Programs