Hijacking Molecular Plasticity to Fine Tune Nuclear Receptor Signaling: Chemical Biology and Precision Therapeutics

This webinar will highlight a new platform for structure-function analysis to dissect activation mechanisms of nuclear receptors (NRs).

Regulation of gene programs controlled by NRs is driven in part by alterations in the conformational ensemble of the receptor upon ligand binding. Dr. Patrick Griffin will describe the development of a structural proteomics platform that includes differential hydrogen/deuterium exchange (HDX), cross-linking mass spectrometry (XL-MS), co-crystallography and SAXS to structure-function studies.

This platform was used to build an integrative structural model for activation of the nuclear receptor RORG (ROR-gamma), a key lineage defining transcription factor in Th17 cells. Results will be presented from chemo-proteomic and structural proteomic studies that investigate the impact of ligand binding on coregulatory engagement and that examine how RORG recognizes sequence specific DNA response elements.

You will learn

How mass spectrometry can answer structural biology questions
What mass spectrometry techniques are useful for structural proteomics
What it takes to build a structural proteomics platform

About the presenter

Dr. Patrick Griffin, Chair of Molecular Medicine

Patrick Griffin received his PhD in Chemistry at the University of Virginia working in Don Hunt’s lab during the birth of biological mass spectrometry and proteomics. In 2004, Patrick joined The Scripps Research Institute (TSRI), Scripps Florida as Professor and in 2007 was named founding Chair of the Department of Molecular Therapeutics. In 2017, he was named Chair of Molecular Medicine. Using mutagenesis, HDX-MS, crystallography, and NMR, Patrick’s research is focused on structure-function of nuclear receptors, enzymes, and membrane receptors.