Supervisor:  Dr Claire Thornton, Dr Helen Stolp

Department:  Comparative Biomedical Sciences



 Hypoxic ischaemic insult (HI) following birth asphyxia results in cellular energy failure, neural cell death and the development of long term disabilities such as cerebral palsy and epilepsy. Although many signalling pathways are triggered, mitochondria act as the hub for these injury responses and defining mitochondrial biodynamics during such cellular stress is key to developing “mitotherapeutics”1.

Mitochondria can adapt to normal and pathological energy demands in a number of ways including through biogenesis, fission, fusion, and by inducing quality control “mitophagy” mechanisms (Figure 1)2. A number of regulatory proteins have been identified; inner and outer mitochondrial membrane fusion are governed by OPA1 and mitofusin1/2 respectively whereas fission is mediated by the cytosolic protein dynamin-related protein (Drp)1. Our recent studies found degraded OPA1 and excessively fissioned mitochondria both in cells in vitro after oxygen/glucose deprivation and in vivo in a mouse model of neonatal brain injury3.

The metabolic sensor, AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase which acts to shut down ATP-consuming, anabolic pathways, promoting ATP-generating, catabolic pathways. As a monitor of cellular and whole body energy status, it is unsurprising that recent studies place AMPK at the heart of the regulation of mitochondrial dynamics4. Furthermore we have found that AMPK activity is rapidly increased in cells and in the brain following in vitro and in vivo HI insult.


Pharmacological modulation of AMPK activity will alter mitochondrial dynamics and subsequently enhance cell survival following HI insult.


  1. To identify the components of mitochondrial fission in neonatal brain (months 1-2)
  2. To evaluate the effect of AMPK activity on mitochondrial fission in cells (months 3-6)
  3. To determine whether pharmacological activators/inhibitors of AMPK alter cell survival following oxygen/glucose deprivation (months 7+)


  1. Hagberg, H., Mallard, C., Rousset, C. I. & Thornton, C. Mitochondria: hub of injury responses in the developing brain. Lancet Neurol 13, 217-232, doi:10.1016/S1474-4422(13)70261-8 (2014).
  2. Thornton, C. et al. Mitochondrial dynamics, mitophagy and biogenesis in neonatal hypoxic-ischaemic brain injury. FEBS Lett 592, 812-830, doi:10.1002/1873-3468.12943 (2018). 
  3. Baburamani, A. A. et al. Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury. International journal of molecular sciences 16, 22509-22526, doi:10.3390/ijms160922509 (2015).
  4. Thornton, C. AMPK: keeping the (power)house in order? Neuronal Signaling 1, NS20160020, doi:10.1042/NS20160020 (2017). 


Applicants should hold, or expect to receive a first or upper second class honours degree in biological or medical sciences, and have an interest in cell biology. Enthusiasm and an eye for detail are prerequisites.

This is a full-time (12 month) project commencing in October 2019, based at RVC's Camden campus.

Partially funded - the lab will be covering some of the project costs, and the MRes student will be expected to meet the outstanding sum required, course fees and their living expenses.

We welcome informal enquiries - these should be directed to

Top of page