Abstract: Series 110, Lecture 3

The Harvey Lectures Series 110 (2014—2015)

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Lecture #3: Thursday, January 22, 2015 — Watch Video of Lecture

From the Cradle to the Grave: My Life in Science Watching Proteins Being Made, Folded and Degraded

Jonathan Weissman, PhD

Jonathan Weissman, PhD

Professor of Cellular and Molecular Pharmacology
Investigator, Howard Hughes Medical Institute

Howard Hughes Medical Institute, University of California, San Francisco

San Francisco, California

Dr Weissman's Website

My laboratory is broadly interested in how cells ensure that proteins fold into their correct shape, as well as the role of protein misfolding in disease and normal physiology. To enable these efforts, we also develop experimental and analytical approaches for exploring the organizational principles of biological systems. I will discuss how our efforts to understand the mechanism and biological role of a yeast prion [PSI+], which regulates translational readthrough, led to the deciphering of general principles of prion-based inheritance. Our desire to understand the biological impact of [PSI+]-mediated translational readthrough also motivated the development of a ribosome profiling assay, based on deep sequencing of ribosome-protected fragments, which has transformed our ability to monitor protein synthesis. I will present recent applications of our ribosome profiling approach including the following: (1) Development of ribosome profiling protocols for a wide variety of eukaryotic and prokaryotic organisms. (2) Uses of ribosome profiling to globally monitor when chaperones, targeting factors or processing enzymes engage nascent chains. (3) Application of ribosome profiling to define the protein coding potential of complex genomes. (4) The development of a proximity-specific ribosome profiling assay for monitoring subcellular localized translation and its use to follow translation on the surface of the endoplasmic reticulum and mitochondria.