Mechanics in cell and tissue organization and function
Rab5 is a master regulator of early endosome biogenesis. Rab5 is necessary for the biogenesis of the entire endo-lysosomal pathway in vivo. It regulates the specificity and directionality of endosome fusion via the recruitment of tethering effectors that lead membranes to dock and fuse. One of the outstanding questions is which are the molecular and physical mechanisms by which membranes are brought together to dock and fuse after capture by a tether. How can long rod-like tethering molecules capture vesicles and yet permit the reduction of the distance between the membranes for fusion? Focusing on the Rab5-EEA1 endosomal machinery using a combination of biochemistry, electron microscopy and biophysics, we discovered that Rab5 induces an allosteric conformational change on EEA1, from extended to flexible, generating an entropic collapse force that helps pulling the membranes together. This means that the function of Rab proteins goes beyond effector recruitment. The mechanism we have uncovered may be widespread in biology (not only vesicle tethering) given the large number of coiled coil proteins in multiple functions.
We are now applying quantitative imaging and functional genomics approaches to explore the mechanisms underlying liver tissue organization and regeneration. Using a combined experiment-theory approach we found a requirement of bile canaliculi (BC) contractility for bile flow in vivo and discovered that the mechanical properties of the BC network play a role in liver regeneration.
The talk will be followed by a refreshments in the WTB LifeSpace to which everyone is invited.
About the speaker:
Zerial Lab. Max Planck Institute of Molecular Cell Biology and Genetics.
Marino Zerial graduated in biology at the University of Trieste in 1982 with a thesis on lysosomal storage disorders. He conducted post-doctoral experiences at the Institut J. Monod (Paris) on the organization of the human genome and at the European Molecular Biology Laboratory, EMBL (Heidelberg) on the biosynthesis and endocytosis of the tranferrin receptor. He became EMBL research Group Leader in 1991, when he started his work on the molecular regulation of endocytosis. In 1998, he became Max Planck Director and co-founder of the Max Planck Institute of Molecular Cell Biology and Genetics, MPI-CBG, Dresden.
Marino Zerial has made key contributions towards the understanding of the molecular mechanisms of endocytosis. Particularly, his work on Rab5 as a master regulator of endosome biogenesis established key principles that are now textbook knowledge.
In the past few years, Zerial’s group has performed a systems analysis of endocytosis using quantitative multi-parametric image analysis, revealing design principles of the endocytic network that are important for signalling. Zerial and colleagues have been developing methods for a multi-scale analysis of tissue organization and function, using the mouse liver as model system.
For his scientific contributions, he was awarded the 1994 FEBS Anniversary Prize, the Chiara D’Onofrio Prize (1999), and the prestigious Gottfried Wilhelm Leibniz Prize (2006). Marino Zerial was elected EMBO Member in 1996 and is Honorary Professor at the Medical Faculty, University of Technology, Dresden.
About the lecture series:
The Bridget Ogilvie Lecture is named after Dame Bridget Ogilvie who was Director of the Wellcome Trust 1991 - 1998 and who played an important role in the development of the College of Life Sciences, in particular in the special award of £10 million that lead to the building of the Wellcome Trust Building in 1997. Each Wellcome funded Division in CLS takes turns in nominating the Bridget Ogilvie Lecturer and this year is the turn of BCDD.