Our group focuses on how PI3Ks are used by cells of the immune system to instruct and coordinate defences against pathogens. PI3K is shorthand for phosphoinositide 3-kinase which means that these enzymes add a phosphate from ATP to the D3 position on a phosphatidylinositol head-group as shown below. The lipid phosphatase Pten removes the phosphate added by PI3K, thus maintain low levels of PIP3 in unstimulated cells.
Projects in the laboratory
What are the individual roles of each of the class I PI3Ks in lymphocytes?Using genetic and pharmacological approaches, we address the functions of individual PI3K isoforms in lymphocytes.
At the molecular level, we investigate the basis for their differential engagement by the TCR, BCR and other receptors expressed by lymphocytes.
We are especially interested in delineating how p110α and p110δ are differentially activated.
How do PI3Ks regulate immune responses to infection?
Using different models of infection, the effect of inhibiting PI3K on protective immune responses will be investigated. This will involve analysis of both APCs and responding T cells and B cells using pathogens such as Listeria monocytogenes and Streptococcus pneumoniae.
The understanding of how PI3Ks control susceptibility to infection is made more pertinent by the discovery that activating mutations in the gene for p110δ are the cause of a primary immunodeficiency disease (APDS)
What is the role of PI3K signalling in regulatory T cells?We have previously shown that inhibition of p110δ in regulatory T cells (Treg) renders ineffective in preventing T cell-mediated inflammation of the large intestine.
More recently we showed that deletion of p110δ in Treg improves immune-mediated rejection of cancer cells.
We are currently exploring further consequences of inhibiting PI3K isoforms specifically in Treg and how PI3Ks affect Treg function.