Role of the cell surface in health and disease

An unexpected discovery resulted from the group’s knowledge of caveolae. They designed a nanoparticle that can deliver medicines through the plasma membrane directly into a cell.

“Nanoparticles have promising applications for vaccine development and drug delivery.”

The end game of the research is to identify the proteins that are mutating within the cell to cause disease, and therefore pinpoint the drug targets for the future, and continue to create new technologies for molecular cell biology. 

Development of a novel drug delivery vehicle

Using our knowledge of caveolae, we worked with as team of international colleagues to generate a novel nanovesicle in bacteria (Cell, 2012). These vesicles can be easily generated in large quantities, encapsulate drugs, and can encode targetting information. The novel vesicular carriers are now being used for both drug delivery and for vaccine development in collaborative work funded by the ARC Centre of Excellence (CoE) in Convergent Bio-Nano Science and Technology.

Journey to the Centre of the Cell; application of Virtual Reality in Cell Biology

We have translated 3D electron microscpic data into a Virtual Reality experience with our CoE collaborators John McGhee (UNSW) and Angus Jonhston (Monash University). This allows a viewer to explore inside a ‘real’ cancer cell in a unique virtual reality experience. This has been widely featured in the media including ABC TV's Catalyst, Fairfax media, New Scientist magazine, and Network Ten's Scope program. 

• Identification of intracellular cavin target proteins reveals cavin-PP1alpha interactions regulate apoptosis

  McMahon, Kerrie-Ann, Wu, Yeping, Gambin, Yann, Sierecki, Emma, Tillu, Vikas A., Hall, Thomas, Martel, Nick, Okano, Satomi, Moradi, Shayli Varasteh, Ruelcke, Jayde E., Ferguson, Charles, Yap, Alpha S., Alexandrov, Kirill, Hill, Michelle M. and Parton, Robert G. (2019). Identification of intracellular cavin target proteins reveals cavin-PP1alpha interactions regulate apoptosis. Nature Communications, 10 (1) 3279, 3279. doi: 10.1038/s41467-019-11111-1

• In vivo cell biological screening identifies an endocytic capture mechanism for T-tubule formation

  Hall, Thomas E., Martel, Nick, Ariotti, Nicholas, Xiong, Zherui, Lo, Harriet P., Ferguson, Charles, Rae, James, Lim, Ye-Wheen and Parton, Robert G. (2020) In vivo cell biological screening identifies an endocytic capture mechanism for T-tubule formation. Nature Communications, 11 1: . doi:10.1038/s41467-020-17486-w

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I have established strong links with my research collaborators nationally and internationally. Many of my collaborations began while at the EMBL in Heidelberg and I am extremely proud that they continue to this day (eg. with Professor Marino Zerial, Max Planck Dresden, Professor Jean Gruenberg, University of Geneva). My involvement in the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology has opened up some of the exciting new linkages that form the basis of the current proposal. Together with Drs. Angus Johnston (Monash) and John McGhee (UNSW) we have translated our 3D EM data obtained from whole cell ultrastructural analyses into a Virtual Reality (VR) experience. This collaboration has been hugely successful and very popular. But this is only the beginning and we can now envisage a new era in which we can populate these simulations with molecular data to examine biological processes, and test key hypotheses in this interactive 3D environment, which is a feature of the Laureate Fellowship program.

I have established strong links with outstanding international collaborators, such as Professor Ludger Johannes, Curie Institute, and Prof. Tom Kirchausen, Harvard University, and the proposed program will strengthen and extend these links. My involvement in the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology has opened up some of the exciting new linkages that form the basis of this proposal. Together with Drs Johnston (Monash) and McGhee (UNSW) we have translated our 3D EM data obtained from whole cell ultrastructural analyses into a VR experience. This collaboration has been very fruitful and our success will be leveraged to extend these simulations to in vivo models and different tissues.

I have made seminal contributions driven primarily by the research interests of my collaborators (e.g. Miaczynska et al, Cell 2004, 407 citations, FWCI 8.22; Takasato et al, Nature 2015, 362 citations, FWCI 13.9). These have included highly cited seminal papers on crucial conserved endocytic proteins (Chavrier et al, Cell 1990, 963 citations; Bucci et al, Cell 1992, 1057 citations), a collaboration which still continues with recent papers in Nature (Murray et al, 2016, 44 citations, FWCI 2.88) and eLife (Hsu et al, 2018, 7 citations, FWCI 2.17). Many of these required development of new techniques. For example, I developed new quantitative electron microscopic techniques to identify nanodomains in the inner leaflet of the plasma membrane, resulting in high profile publications in Nature Cell Biology (Roy et al, 1999, 384 citations; Prior et al, 2001, 400 citations), the Journal of Cell Biology (Prior et al, 2003, 495 citations, FWCI 7.81), and Proceedings of the National Academy of Science. Over the following years, the method has been used in numerous studies by other groups and has resulted in high impact breakthroughs including dissection of the nanoscale organisation of lipid-anchored signalling proteins in the plasma membrane (eg. Zhou et al, Science, 2015; Zhou et al, Cell, 2017).

• ARC grant Making muscle: molecular dissection of membrane domain formation