All major neurodegenerative diseases are characterised by substantial heritability and large-scale genetic efforts have identified variants associated with disease. These often lie in non-coding, regulatory regions and cannot be linked to any functional outcomes.
At the Centre, we have two groups exploring distinct but complementary areas within this scope of research. Read more about each of them below.
Nathan and Alexi
Dr Nathan Skene
Seeking drug targets for neurodegenerative disease with genome-wide directional evidence
The overall aim of my programme is to identify regulatory mechanisms which cause neurodegenerative disorders, along with the cell types in which they act, and determine whether inhibition or activation of the pathway is associated with increased disease risk. The first step will be to define the cell types responsible for initiating or sustaining the disease, the second step will be to identify transcription Factors acting within the disease-associated cells.
Enquiries:
If you have any enquiries about this programme or are interested in joining this group, please contact:
UK DRI Group Leader
Lecturer in Dementia Research, Department of Brain Sciences
Dr Nathan Skene
n.skene@imperial.ac.uk
View Dr Skene's professional web page.
View UK DRI Neurogenomics Lab website.
Dr Alexi Nott
The role of genetic variation in brain ageing and disease
My group have established a protocol for isolating nuclei of specific cell types from human brain tissue to generate promoter-enhancer interactome maps which have given exciting insight into genes influenced by AD-risk variants and revealed probable cell types in which they function. My overarching vision is that human cell type-specific enhancer atlases will reveal the function of disease-risk variants and identify signalling pathways and transcription factors associated with disease.
Enquiries:
If you have any enquiries about this programme or are interested in joining this group, please contact:
UK DRI Group Leader
Lecturer in Neurogenomics, Department of Brain Sciences
Dr Alexi Nott
a.nott@imperial.ac.uk
View Dr Nott's laboratory website
View Dr Nott's professional web page
key objectives
Key Objectives
- Identify cell types and brain regions in which genetic risk variants cause the onset of neurodegenerative disease
- Understand epigenetic and transcriptional consequences of genetic and environmental risk factors for neurodegenerative disease
- Link genetic risk variants to regulatory and functional outcomes
- Investigate selective vulnerability of cell populations to genetic risk factors
- Characterize and understand altered epigenetic regulation in neurodegenerative disease Identify transcription factors acting within disease-associated cells
- Understand how the environment modulates expression of genetic risk for neurodegenerative disease via epigenetic mechanisms
- Elucidate how exogenous stressors interact with genetic risk to regulate the Alzheimer’s disease-associated glial phenotype
- Determine whether effects of major environmental risk factors associated with Parkinson’s disease are mediated through epigenetic regulation
