Understanding membrane function, dynamics and architecture
Eukaryotic cells use membranes to organize their numerous intracellular processes. These membranes are not just inert barriers. They are compositionally and morphologically dynamic, and their shape and topology are intimately tied to organelle function. Essential processes such as intracellular transport, compartmentalisation of metabolic reactions and communication at organelle contact sites are all dependent on properly regulating membrane architecture. Conversely, defects in membrane morphology of different organelles have been linked to various human diseases. Yet the mechanisms that couple membrane architecture to associated cellular functions are poorly understood.
Our current interests focus on the role of membrane architecture at contact sites between two organelles, and dynamic changes of mitochondrial membranes. Organelle contact sites are important for communication and exchange of molecules such as lipids and calcium. Mitochondrial architecture is critical for energy conversion as well as metabolism, and changes in the organisation of mitochondrial membranes are key aspects of many physiological processes, such as cell division or programmed cell death.
We address these topics using correlative light and electron microscopy to combine information on protein composition and dynamics with 3D views of membrane ultrastructure and of protein assemblies. By complementing microscopy with molecular genetics, we seek to provide a mechanistic understanding of how membrane architecture intersects with cellular processes involving inter-organelle communication and changes in organelle structure.
- Ader, N.R., Hoffmann, P.C., Ganeva ,I., Borgeaud, A.C., Wang, C., Youle, R.J., and Kukulski, W. (2019)
Molecular and topological reorganizations in mitochondrial architecture interplay during Bax-mediated steps of apoptosis
Elife 8: pii: e40712
- Bharat, T.A.M., Hoffmann, P.C., and Kukulski, W (2018)
Correlative microscopy of vitreous sections provides insights into BAR-domain organization in situ
Structure 26: 879-886
- Kukulski. W., Picco, A., Specht, T., Briggs, J.A., Kaksonen, M. (2016)
Clathrin modulates vesicle scission, but not invagination shape, in yeast endocytosis.
Elife 5: pii: e16036.
- Kukulski, W., Schorb, M., Kaksonen, M., and Briggs, J.A. (2012)
Plasma membrane reshaping during endocytosis is revealed by time-resolved electron tomography.
Cell 150: 508-520.
- Kukulski, W., Schorb, M., Welsch, S., Picco, A., Kaksonen, M., and Briggs, J.A. (2011)
Correlated fluorescence and 3D electron microscopy with high sensitivity and spatial precision.
J. Cell Biol. 192: 111-119.
- Alicia Borgeaud
- Jessica Chadwick
- Iva Ganeva
- Patrick Hoffmann
- Michael Wozny