Centre for Discovery Brain Sciences
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Dr Barry McColl

The overall goal of our research is to understand neuroimmune mechanisms influencing brain injury, repair and disease in order to identify new targets for treatments.

Dr Barry McColl

UK Dementia Research Institute Fellow & Senior Lecturer

  • Chancellor's Building
  • 49 Little France Crescent
  • Edinburgh EH16 4SB

Contact details

 Personal Profile 

  • 2018-present, UK Dementia Research Institute Fellow & Senior Lecturer, University of Edinburgh
  • 2014-2018, Group Leader, The Roslin Institute, University of Edinburgh
  • 2010-2014, Tenure-track fellow, The Roslin Institute, University of Edinburgh
  • 2008-2010, Postdoctoral research associate, University of Manchester (PIs Douglas Kell, Nancy Rothwell)
  • 2004-2008, Postdoctoral research associate, University of Manchester (PIs Nancy Rothwell, Stuart Allan)
  • 2000-2004 PhD, University of Glasgow (PI Karen Horsburgh)
  • 1996-2000 BSc (Hons) Neuroscience, University of Glasgow

Research Theme

Research 

The overall goal of our research is to understand neuroimmune mechanisms influencing brain injury, repair and disease in order to identify new targets for treatments. We have particular interests in cerebrovascular disease (stroke and vascular cognitive disorders) and neurodegenerative diseases linked to dysfunction of microglia and neuroimmune regulation. Research in the lab largely encompasses three major strands each of which involves a range of molecular, cellular and organismal approaches using preclinical models, human samples and patient-based investigation.

Microglial mechanisms of resilience and susceptibility to neurodegenerative disease

Microglia are the specialised brain resident macrophages with important developmental, physiological and neuroinflammatory functions. Their dysfunction is increasingly implicated in neurodegenerative diseases leading to dementia. Work in our lab has contributed to the growing recognition of considerable diversity in microglial phenotypes in the healthy, ageing and diseased brain. This diversity may predispose to susceptibility or resilience to disease and influence the course of disease in space and time in distinct ways. The discovery of dementia-causing neurodegenerative diseases where mutations in microglial-expressed genes appear causal or increase risk and which show distinctive vulnerability in specific neuroanatomical compartments (particularly white matter), supports a disease-modifying role for microglia in disease. Our work is using models of neurodegenerative disease and human tissue to explore mechanisms that regulate microglial phenotype, how phenotypic diversity confers resilience and susceptibility to disease, and to identify potential therapeutic targets directed at manipulating or restoring microglial function.

Myeloid cells in brain injury and repair

Myeloid cells are the key orchestrators of innate immune responses and inflammation. As in other tissues, inflammation can have harmful effects in the brain that can aggravate injury but some forms of activity by certain subsets of inflammatory cells is important to enable injured brain tissue to heal and promote recovery of function. Our research is examining regulatory factors that control the subtypes of myeloid cells that accumulate in the injured brain (e.g. after ischaemic and haemorrhagic stroke) and their diverse activation states which we believe is crucial to understand the balance between harmful and helpful inflammation and to identify pro-repair/regenerative phenotypes. Using preclinical models, we are also testing the effects of myeloid cell-targeted compounds to manipulate these cells towards tissue repair phenotypes.              

Neuroimmune signalling and systemic immune dysfunction after stroke

Stroke is a leading cause of death and disability and in addition to the brain damage itself, complicating factors have an important bearing on outcome and functional recovery. Pneumonia is common after stroke and is one of the most important stroke complications associated with poor outcome. Our work has contributed to the increasing recognition that stroke can cause suppression of certain aspects of systemic immune function that normally protects us from infection. These changes may partly explain the high risk of pneumonia and other infections in stroke patients and could offer new approaches for prevention. In particular, we study how B cell function may be impaired after stroke including dysfunction of certain subtypes of B cells with innate-like functions providing protection early after infection. Neural signalling, such as via the sympathetic nerves, appears important in driving dysfunction of B cells and other immune cells after stroke and our ongoing work is investigating this brain-to-immune signalling in more detail. We are also investigating if treatments that could rescue B cell function (or compensate for their impairments) could be beneficial in preventing stroke-associated infection.  

Funding

Alzheimer’s Research UK

BBSRC EASTBIO

UK Dementia Research Institute

Medical Research Council

Wellcome Trust

Lab members

Mike Daniels, Postdoctoral research fellow

Alison Harris, Research technician

Adrian Olmos-Alonso, Research fellow

Caoimhe Kirby, PhD student

Clare Latta, PhD student

Lucas Lefevre, Research assistant

Jamie Loan, PhD student

Laura McCulloch, Postdoctoral research fellow

Stefan Szymkowiak, PhD student

Makis Tzioras, PhD student

Collaborations

Prof Stuart Allan, University of Manchester

Prof Rustam Al-Shahi Salman, University of Edinburgh

Dr Paul Brennan, University of Edinburgh

Prof Sam David, McGill University, Montreal

Dr Andrew Greenhalgh, University of Bordeaux

Prof Giles Hardingham, University of Edinburgh

Prof Karen Horsburgh, University of Edinburgh

Prof David Hume, University of Queensland

Prof Alistair Lawrence, The Roslin Institute / Scottish Rural College

Prof Maria Moro, Complutense University of Madrid

Prof Colin Smith, University of Edinburgh

Prof Craig Smith, University of Manchester

Dr Gerry Thompson, University of Edinburgh

Relevant Publications 

McCulloch L, Alfieri A, McColl BW (2018). Experimental Stroke Differentially Affects Discrete Subpopulations of Splenic Macrophages. Front Immunol, 9:1108. https://doi.org/10.3389/fimmu.2018.01108 PMID: 29872438

Manso Y, Holland PR, Kitamura A, Szymkowiak S, Duncombe J, Hennessy E, Searcy JL, Marangoni M, Randall AD, Brown JT, McColl BW, Horsburgh K (2018) Minocycline reduces microgliosis and improves subcortical white matter function in a model of cerebral vascular disease. Glia 66:34-46 https://doi.org/10.1002/glia.23190 PMID: 28722234

Grabert K, McColl BW (2018). Isolation and Phenotyping of Adult Mouse Microglial Cells. Methods Mol Biol, 1784:77-86. https://doi.org/10.1007/978-1-4939-7837-3_7 PMID: 29761389

McQueen J, Ryan TJ, McKay S, Marwick K, Baxter P, Carpanini SM, Wishart TM, Gillingwater TH, Manson JC, Wyllie DJA, Grant SGN, McColl BW, Komiyama NH, Hardingham GE (2017) Pro-death NMDA receptor signaling is promoted by the GluN2B C-terminus independently of Dapk1. eLife 6 https://doi.org/10.7554/eLife.17161

McCulloch L, Smith CJ, McColl BW. Adrenergic-mediated loss of splenic marginal zone B cells contributes to infection susceptibility after stroke (2017) Nat Commun 8:15051https://doi.org/10.1038/ncomms15051 PMID: 28422126

Owens R*, Grabert K*, Davies CL, Alfieri A, Antel JP, Healy LM, McColl BW (2017). Divergent neuroinflammatory regulation of microglial TREM expression and involvement of NF-kappaB. Front Cell Neurosci 11:56 https://doi.org/10.3389/fncel.2017.00056 PMID: 28303091

Grabert K, Michoel T, Karavalos M, Clohisey S, Baillie JK, Stevens MP, Freeman TC, Summers KM, McColl BW (2016) Microglial brain region−dependent diversity and selective regional sensitivities to aging. Nat Neurosci 19:504-516 https://doi.org/10.1038/nn.4222 PMID: 26780511

Giles JA, Greenhalgh AD, Davies CL, Denes A, Shaw T, Coutts G, Rothwell NJ, McColl BW*, Allan SM* (2015) Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity. Eur J Immunol 45:525-530.*authors contributed equally https://doi.org/10.1002/eji.201444748 PMID: 25367678

Small BG*, McColl BW*, Allmendinger R, Pahle J, Lopez-Castejon G, Rothwell NJ, Knowles J, Mendes P, Brough D, Kell DB (2011) Efficient discovery of anti-inflammatory small-molecule combinations using evolutionary computing. Nat Chem Biol 7:902-908 *authors contributed equally https://doi.org/10.1038/nchembio.689 PMID: 22020553

McColl BW, Allan SM, Rothwell NJ (2009) Systemic infection, inflammation and acute ischaemic stroke. Neuroscience 158: 1049-1061. https://doi.org/10.1016/j.neuroscience.2008.08.019  PMID: 18789376