The Univeristy of Melbourne The Royal Melbourne Hopspital

A joint venture between The University of Melbourne and The Royal Melbourne Hospital

EDUCATION

Research Projects

Project: Using transcriptional analyses to understand recognition of tumours by natural killer cells

Brooks Group

NK cells are a major component of the immune response to viral infections and cancer. As such, understanding how they are functionally regulated and the potential to manipulate their function in a clinical setting is of great importance. NK cells respond to virally infected cells or tumor modified cells through recognising down-regulation of HLA-I molecules on their cell surface. Normal cells have high levels of HLA-I on their cell surface, which following engagement of KIR receptors inhibits NK cell activation. However, in settings of virus infection and cancer, HLA-I can be down-regulated, leading to their targeting by NK cells. Detailed analyses shows genetic variability in the quality of this inhibition. Although understood at a cellular level, much less is known about underlying molecular processes that drive these distinct cellular outcomes. Understanding these intracellular pathways offers an opportunity to fine tune NK cell activity in a variety of clinical settings. This project will therefore directly investigate, (a) the strength of KIR-HLA interactions, and (b) how the types of receptors engaged regulates functional responses of primary human NK cells. This project will combine molecular and cellular immunology and offers a number of relevant immunological techniques including cell culture, functional in vitro assays with primary human cells, flow cytometric analysis, cell sorting, RNA extraction, RNASeq library preparation along downstream analysis of transcriptome and further identification of candidate genes.

Contact project supervisor for further
information and application enquiries

Project Supervisor

Professor Andrew Brooks

Project Co-supervisor

Dr Sanda Stankovic, Dr Philippa Saunders

Project availability
PhD/MPhil
Master of Biomedical Science
Honours

Brooks Group

[email protected]

2 vacancies

Themes
Host Pathogens Interactions
Immunology
Viral Infectious Diseases
Cross Cutting Disciplines

The Brooks lab has a broad array of interests, largely centered on the role of immunoreceptors in the regulation of lymphocyte activation. In particular, we are interested in how natural killer cell receptors regulate NK cell and T cell activation and how genetic variation in these receptors along with their HLA-encoded ligands impacts on clinical outcomes in the settings of infection and transplantation.


Brooks Group Current Projects