Primary supervisor: Veronique Miron
Secondary supervisor: James Boardman
Injury to the brain in the perinatal period is a leading cause of lifelong impairment. Preterm birth affects 15 million pregnancies per annum and 10-15% of those born with very low birth weight (<1.5kg) develop cerebral palsy, while 40-50% experience cognitive / behavioural problems. Brain injury at term due to perinatal asphyxia or stroke is also closely associated with life-limiting impairment. Current therapeutic options for perinatal brain injury are limited.
The developing white matter is particularly vulnerable to injury during the perinatal period and this leads to hypomyelination, axonal injury, and reduced connectivity of specific neural systems (without a global failure of brain growth) at a critical point in development. Susceptibility is only partially explained by known environmental and genetic risk factors, and tissue resilience is poorly understood, which hampers the development of new therapies. The focus of our research, based at The Queen’s Medical Research Institute in the MRC Centre for Reproductive Health, is to understand the mechanisms regulating perinatal brain injury and repair in order to develop evaluate neuroprotective and regenerative strategies for fetuses and neonates at risk of brain injury and poor neurodevelopmental outcome. One approach we are taking is to investigate the contribution of inflammation, as it is implicated in driving both white matter injury and repair.
This project will investigate changes in levels of candidate inflammatory factors associated with white matter injury or repair in the cerebrospinal fluid of babies with increased risk of brain injury and development of cerebral palsy, using high-throughput screening. This will be complemented by studies in ex vivo and in vivo experimental models of perinatal brain injury to assess dynamics of regulation and function of candidates with relation to white matter injury or repair. This project will involve the use of high throughput protein expression analyses, mouse models, ex vivo and in vivo modelling of brain injury, cell culture, immunofluorescence, confocal microscopy, molecular biology, potentially complemented by image processing and analysis of human brain magnetic resonance images. We anticipate that this study will help accelerate diagnosis of brain injury in infants together with identification of novel therapeutic targets for the prevention and treatment of such injury to reduce the incidence of cerebral palsy and neurocognitive impairment.
Applicants are expected to have a good honours degree in the sciences (biological, chemical, physical, mathematics, or computational biology / computer science).
The Little France Campus
The MRC Centre for Reproductive Health (CRH) is located on the ground floor of the Queen’s Medical Research Institute on the University of Edinburgh’s Medical Campus at Little France. The MRC CRH enjoys close collaborative links with the other Centres on the Little France Campus including the MRC Centre for Inflammation Research (MRC-CIR); the British Heart Foundation Centre of Excellence in Cardiovascular Science (BHF-CVS), the Clinical Research Imaging Centre (CRIC) and the MRC Centre for Regenerative Medicine (CRM). The campus has a thriving postgraduate community.
Applicants are expected to have a good honours degree in the sciences (biological, chemical or physical), at least UK level of 2.1 or the equivalent from non-UK universities. A Master’s degree in a relevant subject would be an advantage.
How to apply?
Please submit a CV through the Admissions Enquiries form below.
A ‘statement of purpose’/personal statement and details of 3 academic referees will also be requested.
Application deadline 15 February 2016.
Interviews are expected to take place during early March 2016, the successful applicant beginning studies in September/October 2016, providing funding has been secured.
The 3 year MRC funded studentships are open to outstanding UK science graduates wishing to pursue a career in Reproductive Health. The studentship will cover fees at the UK/EU rate and a minimum stipend as directed by the MRC.
This research project will be in direct competition with 7 other projects currently on offer at the MRC-CRH. Usually the project with the best applicant/s will be awarded the funding. The funding is available to UK graduates who can demonstrate ordinary residence in the UK as defined at through the link below.
Boardman JP, Walley A, Ball G, et al. Common genetic variants and risk of brain injury after preterm birth. Pediatrics. 2014 Jun;133(6):e1655-63.
Boardman JP, Craven C, Valappil S, et al. A common neonatal image phenotype predicts adverse neurodevelopmental outcome in children born preterm. Neuroimage. 2010 Aug 15;52(2):409-14.
Boardman JP, Counsell SJ, Rueckert D, et al. Early growth in brain volume is preserved in the majority of preterm infants. Ann Neurol. 2007 Aug;62(2):185-92.
Miron VE, Boyd A, Zhao JW, et al. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat.Neurosci. 2013 16(9), 1211-1218.
Miron VE, Franklin RJM. Macrophages and CNS Remyelination. J. Neurochem 2014. Review, 130(2):165-71.
Miron VE. Dissecting the damaging versus regenerative roles of CNS macrophages: implications for the use of immunomodulatory therapeutics. Reg Med. 2014 Editorial, 8(6), 673-676.
Hagberg H, Mallard C, Ferriero DM, et al. The role of inflammation in perinatal brain injury. Nat Rev Neurol. 2015 Apr;11(4):192-208.
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FTE Category A staff submitted: 206.93
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