Project: Understanding the role of activating Killer cell Immunoglobulin-like Receptors in infection and reproduction
While Natural Killer (NK) cells are best known for their contribution to innate immune responses to viral infection and cancer, increasing evidence suggests that they also play a significant role in reproduction. Their function is governed by the integration of activating and inhibitory signals received through an array of diverse receptors. Among these, members of the Killer cell Immunoglobulin-like Receptor (KIR) family recognise defined groups of Human Leukocyte Antigen (HLA) class I molecules to enable NK cells to sense changes in HLA class I expression following infection or transformation, as well as having a role in mediating placental invasion during pregnancy. Curiously, while the function of inhibitory KIR is well characterised, the role and regulation of activating KIR remains poorly understood despite both being thought to recognise similar or overlapping HLA ligands. This project will therefore examine how NK cells expressing activating or inhibitory KIR differentially respond to HLA loss induced by cytomegalovirus-encoded viral evasins, and whether this response is impacted by the co-expression of other receptors or ligands associated with infection or pregnancy. This project will pair a number of immunological methods including in vitro assays of primary human NK cells and flow cytometric analysis, along with molecular and cellular techniques such as lentiviral transduction of cell lines.
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
Understanding the role of activating Killer cell Immunoglobulin-like Receptors in infection and reproduction
PhD/MPhil, Master of Biomedical Science, Honours