Summary of Research
Neuro-immune interactions in health and disease
Our research is broadly divided into two major inter-related themes:
(i) understanding how interactions between brain and immune cells help regulate normal brain function and
(ii) understanding how immune and inflammatory processes contribute to chronic neurodegeneration and acute brain damage and repair.
Our overall aim is to use this understanding to develop new approaches for preserving healthy brain function, preventing or minimising neurodegeneration and promoting repair and recovery after brain injury in patients.
Bi-directional communication between the CNS and immune system occurs at several spatial scales and is essential for normal function of both systems. At the cellular level within the brain, microglia (the resident macrophages of the CNS) communicate with all other cell types including neurons. Neuronal-microglial communication is a key determinant of neuronal function and also regulates microglial activity. This regulatory control of microglia is important to prevent their transformation to proinflammatory and potentially neurotoxic phenotypes that can contribute to neurodegeneration.
Our work seeks to understand how a novel class of peptides produced by neurons regulates microglial function and contributes to the preservation of neuronal homeostasis. We are also studying how ageing affects neuronal-microglial communication and the transcriptional basis for microglial diversity that enables these cells to adapt to their microenvironment and support neuronal function.
Innate and adaptive immune responses are essential for host defence against infection and tissue repair but inappropriate, excessive or mis-directed inflammatory and immune processes can also cause or exacerbate tissue damage and dysfunction. Extensive evidence implicates inflammation as a pathological mechanism in a range of acute brain injuries (hypoxia, ischaemia, trauma) and chronic neurodegenerative conditions (e.g. Alzheimer’s Disease, Parkinson’s Disease). We aim to understand molecular and cellular inflammatory mechanisms that contribute to acute brain injury and promote neurodegeneration and identify potential therapeutic targets.
Our recent studies have shown how acute or chronic inflammatory conditions originating outside the brain (e.g. infection, vascular disease) can aggravate tissue damage and inflammation after a subsequent brain injury. In addition, a particular interest is to determine mechanisms that regulate inflammation resolution and drive the transition from injury to repair in the post-ischaemic brain. Augmenting pro-resolution pathways may offer benefits over conventional anti-inflammatory approaches because they limit the tissue-damaging consequences of inflammation yet still harness the pro-regenerative properties of inflammation.
We use a range of in vivo and in vitro systems including in vivo models of inflammation, brain injury and chronic neurodegenerative disease and isolation and culture of brain and immune cells. Analytical techniques include flow cytometry, confocal/multiphoton intravital microscopy and computational approaches such as network-based analysis and evolutionary algorithms.