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Regulation and function of cytotoxic lymphocytes


Project Description

In the Voskoboinik laboratory, researchers investigate cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, which play a key role in the surveillance of virus-infected and cancer cells. Clarifying the biology of CTL and NK cells is critical to help understand the fundamental principles of immunity, predisposition to paediatric blood cancers and immune deficiency. We take a multidisciplinary approach that encompasses immunology, biochemistry, structural biology, cell biology and genetics.

Cytotoxic lymphocytes recognize and kill cancerous and virus-infected cells through cytotoxic granule exocytosis pathway. Cytotoxic granules store a pore-forming protein, perforin, and serine proteases, granzymes. Once released, perforin transiently disrupts a target cell membrane thus permitting the delivery of granzymes into the cytosol, where they initiate various apoptotic death pathways. This is a fundamental homoeostatic process and, when disrupted, has catastrophic consequences: it either leads to fatal hyperinflammation or, in milder cases, results in haematological malignancies in childhood or adolescence.

This project will investigate the regulation of cytotoxic granule exocytosis, and the role of disruption of cytotoxic granule exocytosis pathways in haematological malignancies.

A prospective student will be a part of a successful multidisciplinary research team of immunologists, biochemists, cell biologists, geneticists and clinical scientists, and will gain experience in immunology, cell biology (including various microscopy techniques), molecular biology and biochemistry.

Funding Notes

All PhD students at Peter Mac must have a scholarship from The University of Melbourne or through another government, trust or philanthropic organisation. Before applying for a scholarship, you must have agreed on a project with an institute supervisor.

For further information about the university application process, see:
View Website

For further information regarding scholarships (both local and international), see:
View Website
Closing dates for applications for scholarships to commence in 2017: Round 1 -31 October 2016; Round 2 - 18 Dec 2016.



References

Lopez, J.A. et al and Voskoboinik, I. (2013) Blood, 121, 2659-2668.
Brennan, A.J. et al and Voskoboinik, I. (2011) Immunity, 34, 879-892.
Law, R.H.P.*, Lukoyanova, N.*, Voskoboinik, I.* et al. (2010) Nature, 468, 447-51

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