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

Summary 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.

Project Details

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 a 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 how (a) the strength of KIR-HLA interactions and (b) 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.