Aston University bioscientist Dr John Reynolds has won a £125,000 Springboard grant from the Academy of Medical Sciences (AMS) for research into neurodegeneration caused by a rare genetic disease.
Ataxia telangiectasia-like disorder (ATLD) is an inherited neurodegenerative disease with symptoms including jerky, uncoordinated movements, abnormal eye movements and speech difficulties. It is caused by mutations in MRE11, a protein that plays a vital role in repairing damage to DNA. Every cell in the body experiences DNA damage on a daily basis, which the body must repair. MRE11 is central to a number of DNA repair pathways, where it detects and helps repair different forms of DNA damage.
Mutations in MRE11 primarily affect the central nervous system, though the reasons for this are unclear. Dr Reynold's project, 'Fixing breaks in the brain', will investigate why neurons are exceptionally sensitive to failures in DNA repair, the types of DNA damage that are most toxic to neuronal cells, and how defects in MRE11 ultimately lead to neuronal death.
Although ATLD is rare, neurodegeneration itself is a common feature of other diseases, particularly those associated with ageing such as Alzheimer's and Parkinsons. Failures in DNA repair are commonly linked to neurological decline, so by understanding how MRE11 protects neurons from DNA damage and prevents cell death, this research aims to reveal broader principles of neuronal health. The insights could help inform future efforts to understand, prevent, or slow neurodegeneration in more common diseases.
The collaborative project will also include Aston University's Dr Mariaelena Repici, an expert in the cellular and molecular mechanisms underlying neuronal death and neurodegeneration in diseases of the central nervous system, and Professor Rhein Parri, an expert in generating, culturing, and manipulating neuronal model systems to study the function of cells in the brain, as well as Professor Grant Stewart, an expert in rare human diseases associated with defective DNA repair, at the University of Birmingham.
Currently, most experiments on neurons are carried out on cells grown in flat layers. However, Dr Reynolds hopes to use more physiologically relevant model systems, such as brain organoids - 3D mini‑brain tissues grown from human stem cells that better mimic brain architecture and cell diversity - to study MRE11 dysfunction in a context that more closely resembles the human brain. Following a successful funding bid led by Professor Parri in 2023, Aston University has a 3D bioprinter which can print cell cultures and structures like those found in the brain.
Dr Reynolds said:
"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, or why certain regions of the brain are more sensitive to unrepaired DNA damage than others. The drive to answer these longstanding and fundamental questions has been central to my research since my PhD and underpins the long-term vision of my research laboratory."
The latest round of AMS Springboard funding has seen £6.7m awarded to 55 early career researchers at 38 institutions across the UK, backing new research that can transform understanding of Parkinson's, Alzheimer's, infectious diseases and chronic pain, among other pressing health challenges.
AMS's flagship Springboard programme supports curiosity-driven, discovery-stage research - the foundational science that underpins future treatments and interventions. Now in its eleventh year, Springboard supports researchers at a critical point in their careers, when many are establishing laboratories for the first time and need the freedom to explore ambitious questions. It is supported by the UK Government's Department for Science, Innovation and Technology, Wellcome and the British Heart Foundation.
Professor James Naismith, vice-president (non-clinical) at the Academy of Medical Sciences, said:
"The transition to research leadership is one of the most challenging stages in a research career, yet it is also when creativity is often at its strongest. 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. The projects announced today show the impact this approach can have - demonstrating how early support can translate into meaningful benefits for patients, communities and the wider health system."
To tackle cruel diseases like Alzheimer's, Parkinson's and chronic pain, and ultimately save lives, we must help researchers to take their ambitious discovery-stage work to the next level. This support is backing researchers at a stage where attracting commercial investment can be a challenge and builds on the government's record investment in research - unlocking more discoveries that benefit people across the UK and beyond."
Lord Vallance, UK science minister
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