Harnessing Inteins in Chemical Biology

Tom Muir FRS (Princeton University) delivers a seminar on 'Harnessing Inteins in Chemical Biology: From Ligases to Transposases and Logic Gates'

Inteins are auto-processing domains found in organisms from all domains of life. These proteins are consummate molecular escape artists that spontaneously excise themselves, in a traceless manner, from proteins in which they are embedded. Chemical biologists have long exploited various facets of intein reactivity to modify proteins in myriad ways for both basic biological research as well as translational applications. Here Tom Muir will discuss recent efforts to engineer inteins for protein engineering applications in the test tube and in cells. He will also describe the development of an autonomous decision-making protein device driven by proximity-gated protein trans-splicing that can perform various Boolean logic operations on cell surfaces, allowing highly selective recruitment of enzymatic and cytotoxic activities to specific cells within mixed populations.

The Centre for the Physical Science of Life is hosting this event as part of it’s annual events programme.

Tom W. Muir received his BSc in chemistry from the University of Edinburgh in 1989 and his PhD in chemistry from the same institute in 1993 under the direction of Professor Robert Ramage. After postdoc studies with Stephen B.H. Kent at The Scripps Research Institute, he joined the faculty of The Rockefeller University in 1996, where he was, until 2011, the Richard E. Salomon Family Professor and Director of the Pels Center of Chemistry, Biochemistry and Structural Biology. In 2011, Dr. Muir joined the faculty of Princeton University as the Van Zandt Williams Jr. Class of ’65 Professor of Chemistry. He served as Chair of the Chemistry Department until 2020. He is best known for developing methods for the preparation of proteins containing unnatural amino acids, posttranslational modifications and spectroscopic probes. These approaches are now widely employed in academia and industry. His current interests lie in the area of epigenetics, where he tries to illuminate how chemical changes to chromatin drive different cellular phenotypes.

The Centre for the Physical Science of Life realises the transformative power of physical science in advancing understanding of the fundamental mechanisms underlying living systems across scales. We foster an atmosphere of creativity, pioneer new frontiers at discipline interfaces and provide innovative, impactful solutions for pressing societal challenges.

Based in the Faculty of Natural, Mathematical and Engineering Sciences (NMES), the goal of our unique physical science centre is to achieve a whole-scale quantitative understanding of life using physical and mathematical principles. By coalescing expertise across our Faculty in creative fusions of natural, mathematical and engineering sciences, our ambition is to solve the fundamental challenge of modern biology; bridging the gap between current biomolecular and systems level descriptions of biological phenomena. This presents a significant new frontier for physical science tackling emergent behaviour far from equilibrium in sentient systems that self-assemble and evolve.