In recent years, the Hawkins lab has focused on the role of PI3Ks in the signalling mechanisms which allow cell surface receptors on mammalian neutrophils to control various aspects of neutrophil function. Neutrophils are key players in the front line of our immune system, responsible primarily for the recognition and destruction of bacterial and fungal pathogens. However, they are also involved in the amplification cascades that underlie various inflammatory pathologies, e.g. Acute Respiratory Distress Syndrome (ARDS) and rheumatoid arthritis.
Current projects include investigation of the molecular mechanisms which allow different receptor types to activate PI3Ks. In the past similar investigations in neutrophils led to our understanding of how PI3Kγ is regulated by Gβγ subunits and Ras, as well as how integrins and FcγRs regulate PI3Kβ and PI3Kδ within neutrophils.
We are also trying to understand the molecular mechanisms which allow the lipid products of activated PI3Ks to regulate key neutrophil responses. The two main PI3K-dependent responses we are currently focusing on are chemotaxis in gradients of soluble stimuli (Fig 1), which is a crucial mechanism allowing recruitment of neutrophils to sites of inflammation and infection, and activation of the NADPH oxidase.