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 four groups exploring distinct but complementary areas within this scope of research. Read more about each of them below.

Raffaella and Alexi

Dr Raffaella Nativio, UK DRI Group Leader

Dr Raffaella Nativio

Epigenetic pathways in healthy ageing and neurodegeneration

Research in my laboratory is directed towards studying epigenetic regulation in healthy ageing and age-related neurodegeneration. I will perform a series of multi-omics and functional genomics studies in post mortem brain tissue in combination with in vitro experiments to identify epigenetic pathways that modulate (either promote or protect from) Alzheimer’s progression. In vitro experiments will also be performed to identify specific stress response pathways in different brain cell types.


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 Raffaella Nativio
r.nativio@imperial.ac.uk

Dr Alexi Nott, UK DRI Group Leader

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
Dr Alexi Nott
a.nott@imperial.ac.uk
View Dr Nott's laboratory website.

Nathan Skene and Sarah Marzi

Dr Nathan Skene, UK DRI Group Leader

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 Sarah Marzi, UK DRI Emerging Leader

Dr Sarah Marzi

Epigenetic regulation of environmental and genetic risk in neurodegenerative disease


While environmental factors are recognised to be important for neurodegenerative disease outcomes and are known to influence epigenetic regulation, specific epigenetic mechanisms through which environmental factors may promote neurodegeneration have not been defined well. My research will address this knowledge gap directly for the first time by characterizing the epigenetic mechanisms by which environmental risk factors confer disease risk and interact with the underlying genetic risk profile.


Enquiries:

If you have any enquiries about this programme or are interested in joining this group, please contact:

Edmond and Lily Safra Research Fellow
UK DRI Emerging Leader
Dr Sarah Marzi
s.marzi@imperial.ac.uk
View Dr Marzi's professional web page.
View UK DRI Neurogenomics Lab website.

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