Wanda Kukulski

Linking membrane architecture to function by correlative microscopy

kukulski@mrc-lmb.cam.ac.uk

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 endocytosis, intracellular transport, 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.

wk1
How to capture short-lived membrane structures such as vesicles in the endocytic pathway? The vesicle is marked by the presence of a fluorescent protein (red). We can localize its signal by fluorescence microscopy, and then directly image the underlying vesicle by electron tomography

Our current interests focus on membrane dynamics controlling cargo traffic through the network of endosomes, and the role of membrane architecture at contact sites between two organelles. Endosomal sorting is critical for signalling and nutrient uptake, as well as for regulating the composition of the plasma membrane, but it is also hijacked by pathogens for cell entry. Organelle contact sites are important for communication and exchange of molecules such as lipids and calcium.

The specific arrangement of two
apposed membranes is required for
various cell physiological processes
that occur at membrane contacts
between organelles.

 

We address these topics using correlative light and electron microscopy to combine information on protein composition and dynamics with 3D membrane ultrastructure. By complementing microscopy with molecular genetics, we seek to provide a mechanistic understanding of how membrane architecture intersects with cellular processes involving inter-membrane communication and transport.

Selected Papers

Group Members

  • Patrick Hoffmann
  • Nicholas Ader
  • Iva Ganeva
  • Sophie Martin
  • Michael Wozny
  • Alicia Borgeaud