Supervisor:    Claire ThorntonHelen Stolp

Department:  Comparative Biomedical Sciences

  

Project Details

During the first few weeks of life there is a high metabolic demand, especially in the brain, and efficient mitochondrial function is critical for meeting this cellular energy need. Unfortunately, mitochondrial function is targeted by asphyxia during birth, resulting in a bioenergetics crisis in neurons and leading to hypoxic-ischaemic encephalopathy (HIE). This leads to life-changing neurological consequences for 1-2 in every 1000 term babies in the UK, and significantly more in low resource countries. Treatment options are limited and there is an urgent need for new and synergistic therapies.

Impaired mitochondrial efficiency contributes to neuronal death and a subsequent pathological inflammatory response, and treatments which can protect the cellular energy requirement may offer a new avenue for therapeutic intervention. Preliminary data from our lab and others suggest that exogenously applied mitochondria are preferentially taken up by damaged or vulnerable cells and may confer a survival benefit.

The aim of this MRes project is to determine whether, following exposure to hypoxia-ischaemia, cell survival and bioenergetics can be improved by donation of healthy mitochondria to vulnerable recipient neurons.

We are looking for an enthusiastic and motivated student to investigate whether mitochondrial transduction represents a therapeutic avenue of investigation for neonatal brain injury. The student will identify optimal conditions for mitochondrial delivery to neuronal cells, promoting their improved survival following oxygen-glucose deprivation. In addition, the student will evaluate whether extracellular vesicles can be manipulated to act as therapeutic vehicles for transferring mitochondrial cargo into recipient cells. To accomplish this, the student will develop a wide range of lab techniques including cell culture, confocal and live microscopy, enzyme assays and qRT-PCR.

The data obtained in this project will provide evidence to determine whether such mitochondrial transduction therapy could offer neuroprotection for the many infants afflicted with HIE.

  

References

  1. Thornton C, Jones A, Nair S, Aabdien A, Mallard C and Hagberg H. (2018) Mitochondrial dynamics, mitophagy and biogenesis in neonatal hypoxic ischaemic brain injury FEBS Letters 592(5):812-830, doi: 10.1002/1873-3468.12943

  2. Thornton C, Leaw B, Nair S, Mallard C, Jinnai M and Hagberg H. (2017) Cell Death in the Developing Brain after Hypoxia-Ischemia Front Cell Neurosci doi: 10.3389/fncel.2017.00248

  3. Lightowlers RN, Chrzanowska-Lightowlers ZMA and Russell OM (2020) Mitochondrial transplantation—a possible therapeutic for mitochondrial dysfunction? EMBO Reports 21: e50964 doi: 10.15252/embr.202050964

  

Requirements

Essential

Desirable

  • Background in Cell Biology, Biological Sciences or other equivalent

  

This project is full-time and commences in October 2021, based at RVC's Camden campus.

The project may involve the use of animal tissue

  

Funding

Partially funded: the lab will be covering the laboratory project costs, and the MRes student will be expected to meet the course fees and their living expenses.

Please note that EU/EEA and Swiss national students may no longer be eligible for the “Home” rate of tuition fees, dependent on personal circumstances (including immigration status and residence history in the UK) and UK government rules which are currently being developed. For up-to-date information on fees for EU/EEA and Swiss national students following Brexit please see our fees and funding page.

     

How to Apply

For more information on the application process and English Language requirements see How to Apply.

Deadline: 31st July 2021

Interviews will take place remotely over zoom.

We welcome informal enquiries - these should be directed to cthornton@rvc.ac.uk

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