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Regulation and function of cytotoxic lymphocytes


Project Description

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.

The Voskoboinik laboratory investigates 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.
https://www.petermac.org/research/labs/ilia-voskoboinik

Peter MacCallum Cancer Centre, Melbourne Australia
Peter MacCallum Cancer Centre is Australia’s only public hospital solely dedicated to cancer, and home to the largest cancer research group in Australia. Cancer is a complex set of diseases, and modern cancer research institutes such as Peter Mac conduct research covering a diversity of topics that range from laboratory-based studies into the fundamental mechanisms of cell growth, translational studies that seek more accurate cancer diagnosis, clinical trials with novel treatments, and research aimed to improve supportive care.
All students engaged in postgraduate studies at Peter Mac are enrolled in the Comprehensive Cancer PhD (CCPhD) program, regardless of which university they are enrolled through. The program is managed by the Sir Peter MacCallum Department of Oncology (The University of Melbourne), based at Peter Mac.

Tapping into the depth and breadth of knowledge and experience offered by the ten partners of the Victorian Comprehensive Cancer Centre (VCCC) alliance, the University of Melbourne’s Comprehensive Cancer PhD Program provides a unique opportunity for multidisciplinary cancer-related PhD candidates to experience clinical and research activities across the alliance.

The Comprehensive Cancer PhD program builds on established conventional training for cancer research students providing a coordinated program of skills, research and career training in addition to usual PhD activities. The program is designed to complement existing PhD activities and provides opportunities to develop professional skills that will help candidates to fulfil their career ambitions.
https://www.petermac.org/education/comprehensive-cancer-phd-program

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 2019: Round 1 -31 October 2018; Round 2 - 28 Nov 2018; Round 3 - 20 Feb 2019.

References

Voskoboinik I, Whisstock JC and Trapani JA (2015). Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol. 15: 388-400.
Jenkins MR, Rudd-Schmidt JA, Lopez JA, Ramsbottom K, Mannering SI, Andrews DM, Voskoboinik I* and Trapani JA* (2015). Failed CTL/NK cell killing and cytokine hyper-secretion are directly linked through prolonged synapse time. J Exp Med. 212: 307-317. (* equal senior authors)
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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