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MBPhD Programme

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O'Farrell, Fergus Michael

Entered:

September 2011

Current Position: 

Qualified 2017

PhD title: 

Pericyte-mediated regulation of cerebral and coronary blood flow in health and disease

Principal Supervisor: 

Professor David Attwell - Neuroscience, Physiology and Pharmacology

Funding Source: 

Rosetrees Charitable Trust and MRC DTG

Description of Project:

Despite comprising only 2% of the body's mass, the brain must consume 20% of the energy we produce at rest in order to function normally. Increases in brain flood flow, evoked by local neuronal activity, power brain computation and are the basis for functional imaging signals. Pericytes are isolated contractile cells found on capillaries, which can bidirectionally regulate CNS capillary diameter (Peppiatt et al., Nature 2006). Using live imaging, confocal, and two-photon microscopy in brain slices (Mishra et al., Nature Protocols 2014), I am exploring the neuronal-glial-pericyte signalling pathways underlying neurovascular coupling at the capillary level. In vivo, pericytes actively dilate capillaries (before upstream arteriolar smooth muscle dilation), suggesting that they control the brain's energy supply (Hall et al., Nature 2014). However, during ischaemia pericytes irreversibly constrict capillaries and die, impeding reperfusion and contributing to blood-brain barrier injury (Hall et al., Nature 2014). I am elucidating the mechanisms mediating ischaemia-induced pericyte constriction and death, and developing approaches to preventing these processes. Pericytes are also abundant in the heart, where little is known about their function. I am investigating their anatomy, roles in normal coronary physiology, and possible contribution to impaired reperfusion following myocardial infarction (O'Farrell & Attwell., Nature Reviews Cardiology 2014).

Publications:

O'Farrell FM and Attwell D. A role for pericytes in coronary no-reflow. Nature Reviews Cardiology. doi:10.1038/nrcardio.2014.58 Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, O'Farrell FM, Buchan AM, Lauritzen M and Attwell D. Capillary pericyte regulate cerebral blood flow in health and disease. Nature 508: 55-60 (2014) [Link]

Mishra A*, O'Farrell FM*, Reynell C, Hamilton NB, Hall CN and Attwell D. Imaging pericytes and capillary diameter in brain slices and isolated retinae. Nature Protocols 9 (2): 323-336 (2014) [Link] *Equal first authorship

Teaching:

  • Gross anatomy and neuroanatomy demonstrator (2009 - Present)
  • Postgraduate Teaching Assistant (2011 - Present):
  • ANAT 1003: Introduction to Human Anatomy
  • ANAT 2050: Human Anatomy and Embryology
  • ANAT 3038: Advanced Anatomy
  • First and second year MBBS practicals: physiology demonstrator

Awards & Prizes:

Distinction in Medical Sciences (UCL, 2009)
HAB Simons Prize. Best intercalated BSc research project (UCL, 2010)
Dean's List, Faculty of Life Sciences (UCL, 2010)
Evelyn Boesen Prize in Cancer Medicine (UCL, 2011)
William Marsden Scholarship. Best overall performance in MBBS first clinical year examinations (UCL, 2011)