Research themes

Bringing together researchers to address major scientific questions

Themes Pin In Board Red

At the UK DRI, we study a range of neurodegenerative disorders that cause dementia. Many of them share fundamental disease mechanisms and characteristics, and greater understanding gained in one can often benefit others. To ensure we capitalise on diverse expertise, approaches and perspectives, we have established cross-centre themes that bring together researchers to address the major scientific questions that remain in these key topic areas for dementia.

Each theme has a scientific and administrative lead, whose role is to unite researchers and promote collaboration through sharing of knowledge, ideas, resources, best practice and data. Several events take place throughout the year including strategic meetings, workshops and symposia. Early career researchers from the themes organise dedicated activities via steering groups, such as webinar and networking events.

The themes are also a fantastic opportunity to link up with other organisations who share similar research interests. We’ve been thrilled to host collaborative symposia with networks at Dementias Platform UK (DPUK).

Find out more about research themes at the UK DRI in this Q&A with Research Theme Project Manager, Dr Sarmi Sri.

Our current research themes
  • DNA repair

    Scientific theme co-leads: Prof Vincent Dion (UK DRI at Cardiff) & Dr Gabriel Balmus (UK DRI at Cambridge)
    Research theme project manager: Dr Lindsey Caldwell (UK DRI HQ)

    DNA repair mechanisms are crucial to protect the integrity of the genome by identifying and correcting damage. This capacity for repair is thought to decline as we age, contributing to an accumulation of DNA damage. Growing evidence shows genes involved in DNA repair are associated with several neurodegenerative diseases.

    The DNA repair theme is exploring how DNA repair contributes to neurodegeneration and finding ways to target these DNA repair pathways for therapeutics.

    Among the initial areas of focus are Huntington’s disease and repeat expansion disorders, where we:

    - address how somatic instability occurs

    - investigate the progressive deregulation of DNA repair capacity during ageing

    - uncover the emerging interaction between inflammation and DNA repair, and how it may contribute to neurodegeneration

    We aim to take advantage of a greater understanding of these mechanisms to develop treatments directed at reducing repeat expansion or inducing repeat contractions. A major long-term area of interest is to find commonalities with neurodegenerative diseases outside the expanded repeat disorders.

    Find out more about the DNA repair theme in this Q&A article with theme co-leads Prof Dion and Dr Balmus

    Dna repair


  • Informatics

    Scientific theme lead: Prof Caleb Webber (UK DRI at Cardiff)
    Scientific Officer: Dr I-Chun Lin (UK DRI HQ)

    The UK DRI is a data-driven institute. Our researchers are constantly generating large, heterogenous datasets, ranging from -omics, cell/brain imaging, neuronal recordings to patient data. The Informatics theme brings together all those charged with data generation and data analysis, small and large, to exchange expertise and ensure that UK DRI data delivers the maximum clinical and biological knowledge possible. This theme addresses data acquisition and interpretation from the full range of rapidly advancing technologies employed by UK DRI researchers, supporting both occasional and full-time biomedical informaticians.

    Informatics


  • Neuroinflammation

    Scientific theme lead: Prof Paul Morgan (UK DRI at Cardiff)
    Research theme project manager: Dr Lindsey Caldwell (UK DRI HQ)

    Inflammation in the brain is a common feature of all forms of dementia. While this can be helpful in clearing aggregated proteins and cellular debris, it can also contribute to the progression of diseases that cause dementia.

    The Neuroinflammation theme brings together researchers from different scientific backgrounds (including immunologists and neuroscientists) to investigate the role of inflammation in the healthy central nervous system and in the context of neurodegenerative diseases.

    We aim to gain greater understanding as to its importance in protecting the central nervous system and when, where and why it switches to play a detrimental role in the diseases that cause dementia.

    Among the main areas of focus are microglial cells (the resident immune cells of the brain), where we explore:

    - the roles of different microglial subtypes

    - their relevance to pathological protein clearance

    - the involvement of complement components and receptors

    Find out more about one of our Neuroinflammation ECR workshop in this article from 2019

    Neuroinflammation


  • Synapse

    Scientific theme co-leads: Prof Kei Cho (UK DRI at King’s) & Prof Seth Grant (Univ. of Edinburgh)
    Research theme project manager: Dr Sarmi Sri (UK DRI HQ)

    Weakening and loss of normal synaptic function in specific brain regions over time is a key feature of the development and progression of neurodegenerative diseases, and synapse damage and loss precede neuronal loss resulting in cognitive and motor impairments. Despite the major advances in our understanding of the molecular biology of synapses, there is still much to learn about the cause and consequences of synapse damage in neurodegenerative disorders.

    The Synapse theme brings together collective expertise of UK DRI researchers to address major questions surrounding mechanisms of synapse damage from the molecular through to circuit/network levels.

    Among our main questions to unlock new therapeutic and diagnostic opportunities are:

    - why are some synapses vulnerable to neurodegenerative disorders whereas others are resilient?

    - How do microglia target specific synapse subtypes and why this is more pronounced in advanced age?

    - How do toxic protein accumulation, excitotoxicity and metabolic dyshomeostasis (secondary to hypoxia and vascular damage) contribute to synapse damage?

    Read more about the synapse symposium run by UK DRI at King's in 2019

    Synapse

  • Vascular

    Scientific theme lead: Prof Joanna Wardlaw (UK DRI at Edinburgh)
    Research theme project manager: Dr Sarmi Sri (UK DRI HQ)

    Vascular dementia is the second most common cause of dementia. In addition, growing epidemiology, genetic, and neuropathological evidence supports vascular dysfunction as a primary or contributory driver of disease in around 50% of all dementias. Crucially, it appears that vascular dysfunction occurs early in the course of cognitive decline, potentially in advance of neurodegenerative changes, highlighting the vascular component as an attractive and accessible target for intervention.

    The Vascular theme aims to bring together both clinical and preclinical expertise from across the UK DRI and beyond to explore these opportunities further.

    Among our main areas of focus are:

    - vascular contributions to neurodegeneration and dementia in patient cohorts

    - understanding the mechanisms behind vascular and blood-brain barrier dysfunction during ageing and disease (with a strong focus on endothelial cells)

    - greater understanding of the role of glial cells in vascular dysfunction

    Vascular


  • Macroglia

    Scientific theme co-leads: Dr Blanca Diaz-Castro (UK DRI at Edinburgh) & Prof Siddharthan Chandran (UK DRI at Edinburgh)
    Research theme project manager: Dr Lindsey Caldwell (UK DRI HQ)

    Macroglia (including astrocytes, oligodendrocytes, and ependymal cells) are increasingly implicated in the development and progression of dementia. The Macroglia theme brings together researchers from across the UK DRI investigating the role of glia in neurodegenerative diseases. The theme meets to share knowledge, discuss the latest developments in the field, and to identify and address key questions in macroglia biology.

    Through regular meetings, we aim to facilitate discussions to help identify and remove critical roadblocks for understanding how macroglia are involved in neurodegeneration and their potential as targets for novel therapeutic interventions.

    Astrocyte-3D_red-1.jpg#asset:6024

  • Parkinson's disease

    Scientific theme co-leads: Dr Tim Bartels (UK DRI at UCL) & Dr Dayne Beccano-Kelly (UK DRI at Cardiff)
    Research theme project manager: Dr Sarmi Sri (UK DRI HQ)

    Through data-driven focused meetings, the 'Parkinson's disease' Theme aims to facilitate discussions and debates that will help identify and remove critical roadblocks for understanding, diagnosing and treating Parkinson’s Disease and related synucleinopathies. As a group of leading researchers in Parkinson's disease, we will explore some of the following topics:

    - Specific vulnerability of cell types
    - Protein structure and folding
    - Protein homeostasis (proteasome / lysosome)
    - Mechanisms of spread and the gut-brain-axis
    - Biomarkers
    - Neuronal circuits
    - Model systems

    Dopaminergic neuron


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