Dr Barry McColl

The Roslin Institute

Research Interests

Our research is broadly divided into two major inter-related themes:

(i) understanding how interactions between the brain and immune cells help regulate normal brain function

(ii) understanding how immune and inflammatory processes contribute to chronic neurodegeneration and acute brain damage, repair and complications

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

1. Microglial phenotypic diversity

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. We are studying the transcriptional basis for regional microglial diversity that enables them to adapt to their microenvironment and support neuronal function. We are also interested in how ageing affects microglial transcriptional profiles, their regional diversity and the impact of co-existing systemic inflammation.

2. Immune and inflammatory mechanisms of neurodegeneration

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.

3. Resolving inflammation and the balance between injury and repair in the brain after stroke

Stroke causes one in ten of all deaths worldwide and is the leading cause of adult neurological disability. Understanding what influences the transition and balance between injury and repair in the post-ischaemic brain is recognised as one of the most important challenges in the field (e.g. has been referred to as the “new penumbra”). In this context, establishing how pro-injurious inflammation can be contained or resolved without compromising the capacity for endogenous or exogenously-triggered brain repair is essential. We are studying the mechanisms that regulate this balance with a particular focus on the function of the TREM2 protein and interactions among myeloid cell populations in the brain.

4. Stroke-induced immunosuppression

Infection is the most common complication affecting stroke patients and the leading cause of death after the brain injury itself. The reasons for this susceptibility are unclear but may involve suppression of some immune functions involved in host defence to bacterial infection. Our work is investigating how stroke-induced changes in the immune capabilities of lymphoid tissues such as the spleen, notably their ability to capture and process antigen and mount effector responses, may predispose to infection.

 

Selected Publications

  • Rose Owens, Kathleen Grabert, Claire Davies, Alessio Alfieri, Jack P. Antel, Luke M. Healy, Barry McColl. 2017. Divergent neuroinflammatory regulation of microglial TREM expression and involvement of NF-κB. Frontiers in Cellular Neuroscience Vol: 11. More»
  • Laura McCulloch, Craig J Smith, Barry McColl. 2017. Adrenergic-mediated loss of splenic innate-like B cells contributes to infection susceptibility after stroke. Nature Communications Vol: 8. More»
  • Kathleen Renault, Tom Michoel, Michail Karavolos, Sara Clohisey, John Baillie, Mark Stevens, Thomas Freeman, Kim Summers, Barry McColl. 2016. Microglial brain region−dependent diversity and selective regional sensitivities to aging. Nature Neuroscience Vol: 19 Pages: 504-516. More»
  • James A Giles, Andrew D Greenhalgh, Claire Davies, Adam Denes, Tovah Shaw, Graham Coutts, Nancy J Rothwell, Barry W McColl, Stuart M Allan. 2015. Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity. European Journal of Immunology Vol: 45 Pages: 525-530. More»