Edinburgh

​UK DRI at The University of Edinburgh

"The UK DRI at Edinburgh focuses on understanding how all the different cell types in our brains work together to keep the brain healthy, how this goes wrong in dementia, and how this process can be slowed or stopped to alter disease progression." Prof Giles Hardingham
UK DRI Associate Director

1. At a glance

Understanding the inner workings of the brain – and how things can go wrong

UK DRI researchers in Edinburgh are aiming to piece together how all the different brain cells, systems and processes work together to keep our brains healthy over many decades. Unravelling how these finely-tuned interactions are disturbed even before a person has any specific signs or symptoms of dementia – and how changes are involved in driving disease progression – will open new avenues for the development of novel therapies.

Our brain is an incredibly complex organ, made up of around 100 billion neurons and an equal number of other cells that provide vital support and protection. It is aided by an intricate network of blood vessels that supply nutrients and oxygen, working together in perfect harmony. It is essential to understand the function of each component, and the complex relationships between them, to understand how our most complicated organ works – and what happens when things go wrong in conditions such as dementia.

By understanding the inner workings of our brains, the researchers hope to identify disturbances that can lead to neurodegenerative diseases. A main aim of the research programmes is to find new targets for the development of treatments - meaning that more people can live longer, healthier lives.

Read more about the official opening of the UK DRI at Edinburgh

Take a virtual laboratory tour of the UK DRI at Edinburgh

Edinburgh Centre Lab Tour

2. Scientific Goals

The mission of the UK DRI at Edinburgh is to elucidate the interactions within and between the brain vasculature, neurons, macroglia and microglia which control the trajectory of neurodegenerative disorders leading to dementia and exploit this knowledge for therapeutic benefit.

Synapse and circuit dysfunction leading to dementia are heavily influenced by the multicellular environment of the neurogliovascular unit (NGVU). Genetic, epidemiological and post-mortem studies point to inflammatory, vascular and metabolic (mitochondria, lipid, glucose-RNA- and APP- metabolism) factors in pathogenesis. This indicates central roles for NGVU components in disease progression, given their function in maintaining inflammatory, bioenergetic and metabolic balance in the brain.

All NGVU cell types are altered by neurodegenerative disease and its primary risk factor, age. However, the interplay between NGVU components, and their impact on disease progression, is poorly understood, yet critical for progression to therapies. To understand this, it is also important to probe NGVU interactions underlying homeostasis in the healthy brain, which typically maintains human cognitive function for several decades. Identifying the regulators of adaptive and protective homeostatic processes is likely to reveal a largely untapped resource of therapeutic targets with cross-disease applicability.

Achieving this aim will require a holistic view of the NGVU in disease progression, delineating key cell-(non)autonomous influences of disease-causing factors, requiring interdisciplinary, interlinked projects fuelled by complementary expertise.

The centre will develop four inter-related themes through synergistic programmes, exploring how NGVU interactions maintain homeostasis during health, adapt and change during the prodrome, and drive pathology during disease. Scientists will use diverse approaches from animal and human stem cell models through to human imaging and experimental medicine.

The specific themes are:

1. Macroglia in neuroprotection and neurotoxicity

2. Cerebrovascular & metabolic dysfunction

3. Inflammation and immunomodulation

4. Synapses and neurons as effectors of a dysfunctional NGVU

Senior Administrative Team

Beverly Roberts (Scientific Administrator)
Alexa Jury (Laboratory Manager)

3. Collaborations

Within UK DRI

  • Prof Paul Matthews, UK DRI at Imperial
  • Dr Nir Grossman, UK DRI at Imperial
  • Prof Lawrence Rajendran, UK DRI at King's
  • Prof John Hardy, UK DRI at UCL
  • Prof Adrian Isaacs, UK DRI at UCL
  • Prof Sarah Tabrizi, UK DRI at UCL

Beyond UK DRI

4. Topics

Vasculature, inflammation, macroglia, neurons, microglia, synapse

5. Techniques

Mass cytometry, RNA-seq, proteomics, chimeric transplants, Chemogenetics (DREADDs), TRAP-seq, RNA-seq, RNAscope, Forward-Phase Antibody Microarrays, multiplex custom ELISA plates, mass spectrometry, proteomics, primary microglia cell culture (rodent and porcine), multi-species in vitro multi-cell platforms, human iPSC cell culture, MRI, flow cytometry, in vivo multiphoton imaging, MRI, electron microscopy

6. Scientific Advisory Board

7. Vacancies

The UK DRI at Edinburgh is currently looking to recruit excellent researchers to take up UK DRI Group Leaders positions at career-track level. 

Visit our Join Us page to see opportunities available at this centre.

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8. Meet the team

Barry Mc Coll

Barry McColl

  • UK DRI Group Leader
  • Microglial mechanisms influencing susceptibility and resilience to dementia-causing disease
  • Edinburgh
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Beverly Roberts

Beverly Roberts

  • Senior Administrator, UK DRI at Edinburgh
  • Edinburgh
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Blanca Diaz Castro

Blanca Diaz-Castro

  • UK DRI Group Leader
  • Molecular architecture, function and dysfunction of the Blood Brain Barrier
  • Edinburgh
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Bart Man Portrait Dri Navy Copy

Chris Ponting

  • UK DRI Associated Member
  • Computational and Disease Genomics
  • Edinburgh, Collaborators
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Dario Alessi

Dario Alessi

  • UK DRI Associated Member, Dundee
  • Understanding signalling pathways mutated in inherited disorders
  • Edinburgh, Collaborators
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Giles Hardingham

Giles Hardingham

  • UK DRI Associate Director
  • Astrocytes as an upstream modulator and downstream effector of neurodegenerative pathology
  • Edinburgh
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Jian Gan

Jian Gan

  • UK DRI Group Leader
  • Real-time interrogation of neural circuit dynamics underpinning cognition and its collapse in dementia
  • Edinburgh
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Joanna Wardlaw

Joanna Wardlaw

  • UK DRI Group Leader
  • Small vessel disease and vascular contributions to neurodegeneration and dementia
  • Edinburgh
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Josef Priller2

Josef Priller

  • UK DRI Momentum Award
  • Myeloid cells in neurodegenerative diseases
  • Edinburgh, Collaborators
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Seth Grant

Seth Grant

  • UK DRI Associated Member
  • Synaptic proteomic/phospho-proteome analyses in human and rodent brains
  • Edinburgh, Collaborators
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Siddharthan Chandran

Siddharthan Chandran

  • UK DRI Group Leader
  • Dissecting macroglial-neuronal crosstalk in C9ORF72 FTD/ALS
  • Edinburgh
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Tara Spires Jones

Tara Spires-Jones

  • UK DRI Group Leader
  • Non-cell autonomous mechanisms of synapse pathology
  • Edinburgh
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Founding funders

Latest tweets from @UKDRI

We're working across the spectrum of diseases that give rise to dementia 🧠 Explore our group leader profiles and f… https://t.co/5sgOxvh6u9
19 Nov 2019 17:55

RT @jojacksonhere: I wish I had this when I was characterising spine morphology...those long analysis days still haunt me! https://t.co/LJA
19 Nov 2019 17:43