Newborn brain injury: the role of glutamate transporter regulation
Lead Research Organisation:
University of Bristol
Department Name: Clinical Science at South Bristol
Abstract
Brain injury in the newborn period is the leading cause of neurodisability in childhood. Very
recent work from our Bristol Neonatal Gene Study and the ALSPAC birth cohort has found that
genetic variability due to common mutations (single nucleotide polymorphisms; SNPs) in the
gene promotor of the main glutamate transporter (EAAT2) in the newborn brain affects
transporter function and significantly increases vulnerability to brain injury and neurodisability in
babies.
The overarching aim of our work is to develop neuroprotection strategies focussed around
glutamate transport manipulation, initially in small and large animal models, followed by clinical
translation to the first clinical trials in babies.
The hypothesis to be tested for this project is that in the newborn brain DNA methylation of the
EAAT2 gene promotor is vital in regulating EAAT2 function and in resilience to hypoxiaischemia
induced glutamate excitotoxicity.
The student will work with Dr Luyt on the existing Neonatal Gene Study cohort using clinical
data, advanced Magnetic Resonance Imaging data obtained from the babies (brain
volumetrics, measures of white matter injury, neural connectivity) and neurodisability (motor
and cognitive) scores. They will receive training in and use statistical modelling to elucidate the
effect of genetic variability in the EAAT2 promotor on normal brain development and injury.
Findings will be validated in the ALSPAC birth cohort to assess longer-term impact on cognitive function.
recent work from our Bristol Neonatal Gene Study and the ALSPAC birth cohort has found that
genetic variability due to common mutations (single nucleotide polymorphisms; SNPs) in the
gene promotor of the main glutamate transporter (EAAT2) in the newborn brain affects
transporter function and significantly increases vulnerability to brain injury and neurodisability in
babies.
The overarching aim of our work is to develop neuroprotection strategies focussed around
glutamate transport manipulation, initially in small and large animal models, followed by clinical
translation to the first clinical trials in babies.
The hypothesis to be tested for this project is that in the newborn brain DNA methylation of the
EAAT2 gene promotor is vital in regulating EAAT2 function and in resilience to hypoxiaischemia
induced glutamate excitotoxicity.
The student will work with Dr Luyt on the existing Neonatal Gene Study cohort using clinical
data, advanced Magnetic Resonance Imaging data obtained from the babies (brain
volumetrics, measures of white matter injury, neural connectivity) and neurodisability (motor
and cognitive) scores. They will receive training in and use statistical modelling to elucidate the
effect of genetic variability in the EAAT2 promotor on normal brain development and injury.
Findings will be validated in the ALSPAC birth cohort to assess longer-term impact on cognitive function.
People |
ORCID iD |
| Karen Luyt (Primary Supervisor) | |
| Silvia Pregnolato (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N013794/1 | 01/10/2016 | 30/09/2025 | |||
| 1816213 | Studentship | MR/N013794/1 | 01/10/2016 | 17/12/2020 | Silvia Pregnolato |
| Description | Dr Hemmen Sabir - University of Essen |
| Organisation | University Duisburg-Essen |
| Department | Paediatric Neurology |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Processing of biological samples, data collection and analysis |
| Collaborator Contribution | Expertise in running animal model and collection of biological samples |
| Impact | Analysis is still ongoing. No accepted publications yet. This collaboration involves clinicians and basic scientists |
| Start Year | 2018 |
| Description | Final of the 3 Minutes Thesis Competition |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | I was selected for the final of the 3 Minutes Thesis competition and presented in front of about 200 people from the general public at a public venue in Bristol (Colston Hall). After the talk, I had the chance to chat with members of the general public interested in the topic of newborn brain injuries through personal experience, researchers at the university who wanted to know more and even children from the audience who were curious. I was subsequently contacted by a Bristol-based media organisation to make a short video for their website and I am currently liaising with them |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.youtube.com/watch?v=ixPKZfZNy0o&t=33s |