Dan Herschlag

To understand biology, we need chemistry and physics as the physical and chemical properties of biomolecules enable and constrain what biology can do and how it has evolved. We are particularly interested in questions of: (i) how enzymes work; (ii) how RNA folds; (iii) how proteins recognize RNA; (iv) RNA/protein interactions in regulation and control; and (v) the evolution of molecules and molecular interactions. Our interdisciplinary approaches span and integrate physics, chemistry and biology, employ a wide range of techniques, and are question driven. We have new projects in each of the above areas as we:
• Pioneer high-throughput quantitative approaches to study enzymes—to address how an entire protein contributes to its function, how allosteric signals are propagated, how different human alleles affect function and/or stability, and ultimately how to design new enzymes (with Polly Fordyce);
• Work to understand the evolution of enzyme function and stability via functional, genome-scale analyses, and experimental evolutionary studies;
• Pioneer the determination of enzyme conformational ensembles—and linking these to function via novel “ensemble¬–function” studies;
• Develop a quantitative and predictive model for RNA tertiary folding thermodynamics and kinetics, building from the “RNA Reconstitution Model”;
• Provide the first quantitative and complete descriptions of the affinity and specificity of RNA binding proteins for all possible RNA sequences and structures (with Will Greenleaf);
• Pioneer Quantitative Cellular Biochemistry (QCB) to bring together the power of biochemistry and genomics to the study molecular interactions and function in cells, with the goal of providing quantitative and predictive models for molecular function and regulation in cells.