The Wheatstone Lecture is being delivered this year by Professor Viola Vogel (ETH Zurich) entitled ‘Why the mechanical design of proteins matters: from the discovery of physical principles towards the clinic.’
Abstract:
As only the equilibrium structures of proteins have typically been resolved at high resolution, our understanding of biology and in drug discovery is dominated by assuming that each protein has a unique structure which subsequently dictates its function. However, life is happening far away from equilibrium and all life forms are getting exposed to mechanical force. Access to a large set of nanotechnology tools that can probe even the tiniest forces acting on proteins with high precision and others that allow to engineer well defined cellular environments, however, are challenging this notion. Much progress has been made in the molecular understanding of how forces can change the structure of proteins, thereby destroying molecular binding sites or alternatively open them up. Protein stretching is thus exploited by cells to sense and respond to mechanical stimuli and physical factors in their environments which then regulates gene transcription processes and subsequently cell decision making. Translating what has been learned in mechanobiology mostly at the single cell level to real organs, and finally to the clinic, is thereby hampered by at least two challenges: the lack of nanoscale sensors to probe forces or tissue fiber tensions in healthy versus diseased organs. Fundamental molecular mechanisms derived from the usage of experimental and computational tools will be discussed, as well as our efforts to translate such mechanobiological principles into the clinic. Understanding how mechanical forces can switch the structure-function relationships of proteins, and thus cell signalling, is essential to establish the fundamental principles underpinning the rapidly emerging field of mechanobiology.
The lecture will take place in the Great Hall, King's Building, Strand Campus at 17.00