51³Ô¹ÏÍø

Lead RVC Supervisor: Dr. Helen Stolp, Dr. Claire Thornton 

Department: Comparative Biomedical Sciences  

Background, aims and objectives:

In the UK, 10% of all births occur preterm, with 25-30% (~15,000) of these infants subsequently diagnosed with neurological injury that significantly impacts their health, the well-being of their family, and society. There are currently limited treatment options to reduce preterm brain injury, and recent clinical trials have proved largely unsuccessful. However, from these unsuccessful interventions, we have gained increased clarity around mechanisms of injury which offer realistic avenues for intervention.  

The energetic demand in the developing brain is substantial and mitochondria meet such demand by increasing mitochondrial number per cell. Following injury, damaged mitochondria can become significant sources of reactive oxygen species (ROS) which, coupled with impaired respiratory chain function, impact cellular homeostasis. Mitochondria function can be impaired in response to inflammatory cytokines but conversely, can also trigger an immune response through the release of damage-associated molecular patterns such as mitochondrial DNA. We and others have generated substantial data from the developing brain demonstrating that mitochondrial dysfunction, oxidative stress and inflammation escalate perinatal neuropathology. 

We therefore propose that early treatment with a mitochondrial-based therapy will reduce inflammation and improve mitochondrial bioenergetics following inflammatory injury. 

This project aims to introduce a drug into developing neurons that will localize to mitochondria, reducing oxidative stress and cytokine production following inflammatory injury. This will first be performed in cell culture and may subsequently be tested in vivo, if time allows. 

The successful candidate will gain skills in cell culture, immunohistochemistry, microscopy and image analysis (to identify subcellular localisation of drug), assays to assess cell health (including measuring cytokine production and markers of oxidative stress), and Seahorse assays to determine mitochondrial bioenergetics.  

References

1. Fleiss B, Gressens P, Stolp HB. Cortical Gray Matter Injury in Encephalopathy of Prematurity: Link to Neurodevelopmental Disorders. Frontiers in neurology. 2020;11:575. 
2. Dammann O, Leviton A. Intermittent or sustained systemic inflammation and the preterm brain. Pediatr Res. Mar 2014;75(3):376-80. 
3. Hagberg H, Mallard C, Rousset CI, Thornton C. Mitochondria: hub of injury responses in the developing brain. Lancet Neurol. Feb 2014;13(2):217-32. 
4. Nair S, Sobotka KS, Joshi P, et al. Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo. Glia. Jun 2019;67(6):1047-1061.  

Requirements

Essential:

• Must meet our standard MRes entry requirements. 
• Must have a BSc or equivalent degree in neuroscience or a related field of biological sciences.  

Desirable:

• Good organizational skills and enthusiasm.
• Prior experience with cell culture or molecular biology is desirable 

The project may include immunohistochemistry using previously prepared mouse brain sections.  

Fees and Funding

This can be taken full-time (12months FTE) project commencing in October 2025, based at RVC's Camden campus. 

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

International applicants are welcome to apply but must be able to fund the difference between "51³Ô¹ÏÍø" and "Overseas" tuition fees.  

Please note that EU/EEA and Swiss national students may no longer be eligible for the “51³Ô¹ÏÍø” 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 p²¹²µ±ð.

How to Apply

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

Deadline: 04/04/2025

Interviews will take place remotely (Teams, Zoom etc) within 4 weeks of the closing date. 

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