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The role of co-signalling receptors in cytotoxic lymphocyte activity during infection and cancer

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Cytotoxic lymphocytes (CD8+ T and natural killer (NK) cells) are integral for immune protection against infection and in the immunosurveillance of cancer. The activation of T cells, and the cytotoxic activity of T and NK cells, relies on the formation of an immunological synapse with antigen-presenting cells, or target cells, respectively. During synapse formation, T and NK cell activation and function is fine-tuned by a range of co-signalling molecules that positively or negatively modulate lymphocyte activity. Two important receptors in the regulation of T and NK cell function are the co-signalling molecules, DNAM-1 and CD96. We have evidence that tumour cells, such as acute myeloid leukemic (AML) cells, down-regulate the expression of ligands recognised by DNAM-1 and CD96 as an immune evasion mechanism.

Preliminary data show that DNAM-1 is necessary for cytotoxic lymphocyte adhesion and synapse formation during target cell killing. This project will investigate the role of both DNAM-1 and CD96 in T cell responses to antigen, and in T and NK cell cytotoxic activity. We will also investigate the consequences of ligand expression on DNAM-1 and CD96 on NK recognition and killing of AML cells.

The aims of this project will be to:
(1) Investigate the role of DNAM-1 and CD96 in immunological synapse formation and tumour cell killing in vitro
(2) Examine the anti-tumour response in CD96 deficient mice

Techniques commonly used in this laboratory include:Tissue culture, flow cytometry, cell sorting, fixed and time-lapse confocal microscopy, cytokine assays, killing assays, real-time PCR, western blotting, mouse experimentation and general immunological techniques.

In the Oliaro laboratory, researchers investigate the regulation of cytotoxic lymphocytes – the immune cells that are responsible for the recognition and killing of cancer cells. Our research focuses on investigating immune cell interactions with cancer cells, with a particular focus on immune synapse formation.

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.

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