Understanding the role of the DNA damage response in neurodegeneration and brain ageing.
Mature neurons face a distinctive challenge: they must preserve their genetic material throughout life. We investigate how the DNA damage response is organised in these cells, and what happens when repair pathways are disrupted.
Our goal is to understand the mechanisms connecting endogenous genotoxic stress, neuronal dysfunction and degeneration.
We investigate how DNA repair pathways modify the expansion of CAG repeats in the HTT gene. Using CRISPR–Cas9 in human induced pluripotent stem cells and mouse embryonic stem cell models, we explore which genes promote or restrict repeat expansion.
Working with collaborators in Sarah Tabrizi’s laboratory, we aim to define the repair networks involved and identify opportunities for intervention.
We study the contribution of genomic instability to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), including the accumulation of DNA double-strand breaks in neurons.
By comparing DNA damage responses in dividing and non-dividing cells, we investigate how repair is organised in mature neurons and which mechanisms influence their vulnerability.
We develop neuronal models to understand the role of ATM in maintaining genome stability and responding to endogenous damage, including oxidative stress.
Combining these models with genome-wide CRISPR–Cas9 screens helps us investigate the molecular functions of ATM and identify potential disease-modifying suppressors.
We explore how oxidative stress and other endogenous sources of damage affect neuronal survival in Parkinson’s disease.
Our work examines the mechanisms that maintain nuclear and mitochondrial genome stability, and how their disruption contributes to the vulnerability of neurons.
We are interested in how the brain ages, why some neurons become vulnerable, and how brain health can be maintained throughout life. Our work on the naked mole-rat, a remarkably long-lived rodent, provides a way to explore the biology of healthy brain ageing.
A central question is how genome maintenance and responses to DNA damage relate to the preservation of neuronal function with age. By connecting our ageing and neurodegeneration research, we aim to understand the mechanisms that support long-term neuronal resilience and identify opportunities to protect the ageing brain.
We combine CRISPR–Cas9 screening with human stem-cell-derived neuronal models and mouse models of disease. These complementary systems allow us to test how genes and pathways influence damage responses and neuronal survival. Our work on the naked mole-rat adds a comparative perspective on healthy brain ageing.
Explore our publicationsFor research enquiries and collaboration.