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 all depend on properly regulating membrane architecture. Conversely, defects in membrane organization 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 research focuses on the role of membrane architecture at contact sites between two organelles, and dynamic changes of mitochondrial membranes. Organelle contact sites are important for the exchange of molecules such as lipids and calcium, facilitated by specialised proteins that localise at the contact sites between organelles. 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. Specific proteins interact with mitochondrial membranes at particular time points or locations to mediate such reorganisations.
We aim to understand how the function and spatial arrangement of protein molecules interplay with the organisation and ultrastructure of a membrane, and how these relationships drive cellular processes. 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 and biochemistry, we seek to provide a mechanistic understanding of how membrane architecture intersects with cellular processes involving inter-organelle exchange and changes in organelle structure.
Hoffmann P.C.*, Giandomenico S.L.*, Ganeva I., Wozny M.R., Sutcliffe M., Lancaster M.A.** and Kukulski W. 2021.** Electron cryo-tomography reveals the subcellular architecture of growing axons in human brain organoids. eLife 10. pii: e70269 *equal contribution **equal contribution
Wozny M.R. and Kukulski W. 2021. Molecular visualization of cellular complexity. Nature Methods 18:442-443
Ganeva I. and Kukulski W. 2020. Membrane architecture in the spotlight of correlative microscopy. Trends in Cell Biology 30:577-587
Hoffmann P.C., Bharat T.A.M., Wozny M.R., Boulanger, J., Miller E.A., and Kukulski W. 2019. Tricalbins contribute to cellular lipid flux and form curved ER-PM contacts that are bridged by rod-shaped structures. Developmental Cell 51:488-502.e8
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.e3.
Kukulski W.*, Picco A.*, Specht T., Briggs J.A.G., and Kaksonen M. 2016. Clathrin modulates vesicle scission, but not invagination shape, in yeast endocytosis. eLife 16036. *equal contribution
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.