Studies in Cell-Projection Pumping

Summary

Cell-projection pumping (CPP) is a mechanism we have recently discovered whereby cells pump cytoplasm between each other. We have discovered this in context of cancer, where there is predominant transfer of cytoplasm from normal cells (fibroblasts) to cancer cells. We have described this with combined: live cell fluorescence microscopy; mathematical modelling; and computer simulation. We found that CPP uptake of fibroblast cytoplasm by cancer cells increases cancer cell migration, cell division, and morphological diversity. This strongly suggests that CPP is important in development of the disease. Further, our preliminary data suggest roles for CPP in evading both chemotherapy and immunotherapy. From the above, inhibition of CPP could dramatically improve outcomes for cancer patients. This opens a totally new line of investigation for anti-cancer drugs, built about inhibiting CPP. Although we now have a reasonable concept of how CPP occurs, there is much fundamental discovery yet to make on many very basic aspects. For example, while we have demonstrated bulk cytoplasm and membrane transfer: we have not characterized the precise organelles, proteins and RNA species involved; the mechanism for micro-fusion critical for CPP to occur, remains unexplored; and the probable epigenetic basis for persistent change in phenotype, has yet to be examined. Further, cancer never invents a truly new biology, but instead perverts normal processes, so that the question arises as to the possible normal biological function of CPP. For a variety of reasons, we suspect a role in stem cell biology, while we also envisage an important role of CPP in viral infection. From this, it is obvious that there are numerous exciting PhD projects, that can grow from further study of CPP.

Supervisor(s)

Professor Hans Zoellner

Research Location

Sydney Dental School

Program Type

Masters/PHD

Synopsis

Projects exploring cell-projection pumping (CPP) are:
• The role of CPP in protecting against chemotherapy and immunotherapy
• CPP in tissues as opposed to and compared with isolated cell culture
• Mathematical and biophysical analysis and modelling of the mechanism
• Proteins, RNA and organelles transferred
• Study of the epigenetic changes
• Membrane micro-fusions in CPP
• The role of CPP in viral infection
• CPP in stem cell biology
• The structural and ultrastructural basis for CPP

Additional Information

This broad project area entails a very wide scope of separate discrete projects, any one of which could be pursued as a PhD or Masters. Students interested in joining the team, would meet with Professor Zoellner to discuss their personal interests and proclivities, to select whichever aspect of the work is most suitable and of greatest interest for the individual student.

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Keywords

Cell-projection pumping, Cancer, chemotherapy, immunotherapy, Stromal-cancer cell interactions Viral infection, Stem Cell Biology, epigenetics, microscopy, molecular biology, protein chemistry

Opportunity ID

The opportunity ID for this research opportunity is: 2801

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