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 and how these are affected by ageing

(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. Neuronal-microglial communication

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.

3. 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.

4. 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.

5. 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.

6. Imaging neuroimmune activity in vivo

Establishing methods to visualise and quantify dynamic neural and immune processes is essential to complement conventional “static” approaches. We are using intravital multiphoton imaging to study the dynamic behaviour of immune cells within their natural environment and determine how ageing affects this activity. Our aim is to continue to develop our high resolution in vivo imaging capabilities and apply these techniques throughout our projects e.g. to study dynamic events during inflammation resolution in the brain and stroke-induce impairments in splenic immune cell function.

Selected Publications

  • Barry W. McColl, Nancy J. Rothwell, Stuart M. Allan. 2008. Systemic inflammation alters the kinetics of cerebrovascular tight junction disruption after experimental stroke in mice. Journal of Neuroscience Vol: 28 Pages: 9451-9462. More»
  • Barry W. McColl, Nicola Rose, Fiona H. Robson, Nancy J. Rothwell, Catherine B. Lawrence. 2010. Increased brain microvascular MMP-9 and incidence of haemorrhagic transformation in obese mice after experimental stroke. Journal of Cerebral Blood Flow and Metabolism Vol: 30 Pages: 267-272. More»
  • Katie Z Chapman, Verity Q Dale, Adám Dénes, Gavin Bennett, Nancy J Rothwell, Stuart M Allan, Barry W McColl. 2009. A rapid and transient peripheral inflammatory response precedes brain inflammation after experimental stroke. Journal of Cerebral Blood Flow and Metabolism Vol: 29 Pages: 1764-1768. More»
  • B.G. Small, B.W. McColl, R. Allmendinger, J. Pahle, G. Lopez-Castejon, N.J. Rothwell, J. Knowles, P. Mendes, D. Brough, D.B. Kell. 2011. Efficient discovery of anti-inflammatory small-molecule combinations using evolutionary computing. Nature Chemical Biology Vol: 7 Pages: 902-908. More»
  • P. Thornton, B. W. McColl, A. Greenhalgh, A. Denes, S. M. Allan, N. J. Rothwell. 2010. Platelet interleukin-1alpha drives cerebrovascular inflammation. Blood Vol: 115 Pages: 3632-3639. More»