Role of the cell surface in health and disease

To understand the cell is to understand life

Life is built with cells. Within the human body, there are 30 trillion cells and 200 different cell types. How does a healthy cell function? How do cells become specialised? What goes wrong with a cell in disease?

The Parton Group is studying the plasma membrane around the outside of cells.

The membrane is the interface between the cell and the outside world. It stops unwanted things getting into the cell while allowing nutrients and signals to penetrate.

The membrane is covered with crater-like indents called caveolae. The plasma membrane of cells is one of the most abundant structures in our biology – and yet we still don’t understand how it works.

Research overview

“We are examining how the cell structure works, and how it relates to different disease conditions. To tackle problems, we have to understand them first,” said Professor Rob Parton.

The Parton Group are developing new techniques using electron microscopy and virtual reality to construct interactive models of human cells.

“Using this technique we can develop a picture of the membranes of the cell in 3D and then using virtual reality, go into the cell to look around. It is a beautiful world at the cellular level.

“To understand the building block of life is to understand life itself. If we determine what is happening at the cellular level, it will have applications for all diseases.”

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.

The Parton Group progress their discoveries from model systems right through to the animal.

Research projects

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Engagement and impact

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 mediaNew Scientist magazine, and Network Ten's Scope program.

Partners and collaborators

At the European Molecular Biology Laboratory (EMBL) in Heidelberg, Professor Parton was mentored by Gareth Griffiths, where he honed his skills in electron microscopy while collaborating with other groups throughout the institute including Jean Gruenberg and Marino Zerial. He has maintained these collaborations to this day, despite the groups now being spread around the globe.

Collaboration has been central to his career. In a collaborative project with the laboratory of Kai Simons, he observed that the newly-discovered protein, VIP21 (later renamed caveolin-1), was an abundant marker protein of caveolae. Also at the EMBL Parton and Michael Way discovered a second member of the caveolin family, M-caveolin, now termed caveolin-3.

At The University of Queensland he collaborated with Professor John Hancock. Together they showed that caveolin mutants can act as dominant negative inhibitory mutants and that one of the mutants was a highly potent inhibitor of Ras signalling. Inhibition was specific to the palmitoylated form of Ras, H-ras, with no effect on the related but non-palmitoylated isoform, K-ras. The close collaboration between his laboratory and Prof. Hancock’s, led to high profile publications including Nature Cell Biology and the Journal of Cell Biology  over the following years. Their studies generated a new concept in cell biology; dynamic lipid raft association regulated by the GTPase state of the Ras protein. The novel technique developed with John Hancock, involved a statistical analysis of the spatial distribution of proteins on the surface of the plasma membrane and provided a completely unbiased quantitative analysis of the distribution of proteins.

Professor Parton examined whether liver regeneration is affected in caveolin-1 null mice. In an important paper published in Science, Parton and his Spanish collaborators (lead by Dr Pol who had just moved back to Spain after a highly productive postdoctoral visit to Parton’s lab) showed that the liver of caveolin-null mice cannot regenerate efficiently, mortality is high, lipid droplets do not accumulate, and cell cycle progression is perturbed.

 

Prof Rob Parton

Professor Rob Parton

Group Leader, Cell Biology and Molecular Medicine Division, IMB

  +61 7 3346 2032  
  r.parton@imb.uq.edu.au
  IMB Researcher Profile


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