Aston University Scientist Awarded £125k Grant to Probe Brain Degeneration

Dr. John Reynolds, a bioscientist at Aston University, has received a £125,000 Springboard grant from the Academy of Medical Sciences (AMS) to investigate the mechanisms of neurodegeneration in a rare genetic disease. The research could have significant implications for understanding more common conditions like Alzheimer's and Parkinson's.

The funding will support a project titled 'Fixing breaks in the brain', which focuses on neurodegeneration caused by ataxia telangiectasia-like disorder (ATLD).

The Research Focus: ATLD and DNA Repair

ATLD is a rare, inherited neurodegenerative disease. Symptoms can include uncoordinated movements, abnormal eye movements, and speech difficulties. The disorder is caused by mutations in the MRE11 protein, which plays a central role in repairing DNA damage within cells.

The project aims to investigate three core questions: why neurons are particularly sensitive to failures in DNA repair; which types of DNA damage are most toxic to neuronal cells; and how defects in the MRE11 protein lead to neuronal death.

Broader Implications for Brain Health

While ATLD itself is rare, neurodegeneration is a common feature of other widespread diseases. Failures in DNA repair are frequently linked to neurological decline across various conditions.

"Despite more than 30 years of research into diseases caused by mutations in DNA repair pathways, we still do not fully understand why the brain is particularly sensitive to the loss of DNA repair," said Dr. Reynolds.

The research therefore aims to uncover broader principles of neuronal health that could inform future efforts to understand, prevent, or slow neurodegeneration in more common diseases.

Innovative Methods and Collaboration

To study MRE11 dysfunction, Dr. Reynolds plans to use brain organoids—3D mini-brain tissues grown from human stem cells. These models are considered more physiologically relevant than traditional flat cell layers.

Aston University has a 3D bioprinter, acquired following a funding bid in 2023, which can be used to print cell cultures and structures similar to those found in the brain.

The project is a collaborative effort involving:

• Dr. Mariaelena Repici (Aston University), an expert in the cellular and molecular mechanisms of neurodegeneration.
• Professor Rhein Parri (Aston University), an expert in generating and manipulating neuronal model systems.
• Professor Grant Stewart (University of Birmingham), an expert in rare human diseases associated with defective DNA repair.

Supporting Early-Career Research

The AMS Springboard programme supports curiosity-driven, discovery-stage research for early-career researchers. Now in its eleventh year, the programme is supported by the UK Government's Department for Science, Innovation and Technology, Wellcome, and the British Heart Foundation.

"Springboard invests in people at the moment when bold ideas begin to take shape, providing the freedom, confidence and backing researchers need to strike out on their own and ask big questions," said Professor James Naismith of the Academy of Medical Sciences.

In its latest funding round, the programme awarded a total of £6.7 million to 55 early-career researchers based at 38 institutions across the UK.