For further information visit our lab-homepage at zeriallab.org
The Zerial group works on endocytosis - from its molecular mechanisms to implications in cell and tissue organization. Our interests range from the assembly and functional characterization of the endosomal fusion machinery to the establishment of hepatocyte cell polarity and liver tissue structure and function. Our group uses a unique interdisciplinary approach combining biochemical and biophysical methods with advanced light microscopy, cell biology and computer-aided three-dimensional tissue reconstruction.
Our research group pioneered the functional analysis of the Rab family of small GTPases in intracellular transport with a special focus on Rab5. Rab5 and its effector proteins play a key role in endosomal membrane fusion. By reconstituting an endosomal tethering machinery in vitro, we uncovered a new mechanism in which Rab5 induces a change in flexibility of the membrane tether EEA1, generating an entropic collapse force that pulls the captured vesicle towards the target membrane leading to membrane fusion. We also succeeded in reconstituting a synthetic endosome that recapitulates the functional properties of the cellular organelle. Now, we aim at elucidating the molecular mechanism at each step of the process.
In recent years, our research interest broadened from molecular mechanisms to cell and tissue function. We work mainly on mouse liver as a model organ because of its extraordinary features of tissue organization and cell polarization and regeneration potential. Currently, we are especially interested in the role of the endosomal pathway in cell polarity establishment and tissue formation. We are furthermore exploring the mechanisms of tissue regeneration and organization.
In our research, we use an interdisciplinary approach combining state-of-the-art microscopy techniques and development of advanced computer-aided 3D tissue reconstruction algorithms to understand the structure-function relationship of liver tissue. Using this approach, we advanced the understanding of liver tissue organization and predicted alterations occurring in liver disease.
Our long-term goal is to develop a theory of liver tissue organization integrating different scales - from the molecular to the organ scale - and use it to predict tissue structure and function in health and disease.
In medicine, the use of biologically active macromolecules as therapeutics is becoming a widely used strategy. Cells take up macromolecules via the endocytic pathway and traffic them to their specific site of action within the cell. Currently, uptake and endosomal escape of the molecule from vesicles into the cytoplasm are still poorly understood and challenging steps in drug development and delivery. Therefore, our lab has been exploring uptake mechanisms and endosomal escape in various collaborations with pharmaceutical companies. Our expertise in endosomal trafficking and membrane fusion allows us to use bio-inspired approaches to improve macromolecule delivery systems.
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