Annual Frontiers in Chemical Biology Symposium

Michelle Chang, PhD
Professor of Chemistry
College of Chemistry
UC Berkeley

“Synthetic Biology Approaches to New Chemistry" 

Abstract: Living systems have evolved the capacity to carry out many chemical transformations of interest to synthetic chemistry if they could be redesigned for targeted purposes. However, our ability to mix and match enzymes to construct de novo pathways for the cellular production of small molecule targets is limited by insufficient understanding how chemistry works inside a living cell. Our group is interested in using synthetic biology as a platform to study how enzymes function in vivo and to use this understanding to build new synthetic pathways for the production of pharmaceuticals, nanomaterials, and fuels using living cells.

Benjamin Cravatt, PhD
Professor and Gilula Chair of Chemical Biology
Department of Chemistry
Scripps Research

"Activity-Based Proteomics – Protein and Ligand Discovery on a Global Scale"

Abstract: Advances in DNA sequencing have radically accelerated our understanding of the genetic basis of human disease. However, many of human genes encode proteins that remain uncharacterized and lack selective small-molecule probes. The functional annotation of these proteins should enrich our knowledge of the biochemical pathways that support human physiology and disease, as well as lead to the discovery of new therapeutic targets. To address these problems, we have introduced chemical proteomic technologies that globally profile the functional state of proteins in native biological systems. Prominent among these methods is activity-based protein profiling (ABPP), which utilizes chemical probes to map the activity state of large numbers of proteins in parallel. In this lecture, I will describe the application of ABPP to discover and functionally annotate proteins in mammalian physiology and disease. I will also discuss the generation and implementation of advanced ABPP platforms for proteome-wide ligand discovery and how the integration of these global ‘ligandability’ maps with emergent human genetic information can expand the druggable fraction of the human proteome for basic and translational research objectives.

Judith Klinman, PhD 
Chancellor's Professor 
Professor of Graduate School
UC Berkeley

Tunneling, Protein Motions and New Models for Catalysis”

Abstract: The observation that hydrogen transfer occurs by quantum mechanical tunneling across all classes of C-H activation (H⁺, H:^- and H^. transfer) has fundamental consequences for our views of enzyme catalysis. A key feature is the inherent temperature independence of the movement of hydrogen as a wave, implicating the “environment” as the source of the enthalpic barrier to catalysis. Modified versions of Marcus theory for electron transfer have emerged to explain the tunneling rate, and these can be applied to the enzymatic k_cat by incorporating a term that accounts for the fact that catalysis is also determined by the (small) fraction of enzymatic sub- states that achieve catalytically relevant states. Experimental methods have been developed to first obtain spatial resolution of thermal conduit(s) that lead from solvent to the enzyme active site and second to study the role of these conduits via kinetic measurements such as temperature dependent (ns-ps) Stokes shifts and (μs) FRET. The talk will conclude with emerging examples of thermal conduits within many different classes of enzyme reactions, extending the picture of catalytic origins from C-H activation to enzymes in general. A co- evolution of thermal conduits with active site chemistry both expands our fundamental understanding of enzymes and may provide new approaches to enzyme redesign.

Tom Muir, PhD
Professor
Department of Chemistry
Princeton University

“Painting Chromatin with Synthetic Protein Chemistry”

Abstract:Understanding protein function is at the heart of experimental biology. Perhaps one of grandest contemporary challenges in this area is to catalogue and then functionally characterize protein post-translational modifications (PTMs). Modern analytical techniques reveal that most, if not all, proteins are modified at some point; it is nature’s way of imposing functional diversity on a polypeptide chain. Understanding the structural and functional consequences of all these PTMs is a devilishly hard problem. While standard molecular biology methods are of limited utility in this regard, modern protein chemistry has provided powerful methods that allow the detailed interrogation of protein PTMs. In this lecture, I will highlight the use of high-throughput methods for studying the role of PTMs in regulating aspects of chromatin biology. In particular, I will discuss how histone modifications, and cancer-associated mutations, impact the activity of chromatin modifying enzymes and chromatin remodeling machines.