King's College London

UK DRI at King’s College London

"The UK DRI at King's is mapping out the earliest changes in the brain associated with FTD and ALS to gain a much deeper understanding of the causes of these conditions." Prof Chris Shaw
UK DRI Associate Director

1. At a glance

Researchers at the UK DRI at King's are using innovative approaches to explore the biological mechanisms involved in neurodegenerative diseases. Their goal is to defeat dementia by uncovering vital new knowledge that will lead to the design of smarter diagnostics and effective treatments.

The UK DRI at King's is aiming to understand the fundamental biological processes involved in dementia at a molecular level – and to use that knowledge to design new ways to diagnose and treat disease more precisely.

The researchers are initially focusing their investigations on three neurodegenerative diseases: Alzheimer’s disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). While these are clinically distinct conditions affecting different areas of the nervous system, they all involve the death of neurons and share considerable overlap in their clinical features and molecular causes.

The process of neurodegeneration occurs due to a gradual loss of neuronal structure and function that, during disease progression, ultimately results in cell death. Although the processes behind this aren’t yet fully understood, a build-up of toxic proteins and the loss of connections (synapses) between neurons are both intimately involved.

The team is using cutting-edge techniques to study the role of key genes and proteins in neurodegeneration. These include advanced imaging tools that allow them to look at what’s going on inside neurons at the level of individual molecules. They hope to build a better picture of the molecular causes of different diseases and use this to design and develop innovative new treatments that can tackle dementia.

Read more about the official opening of the UK DRI at King's

Visit UK DRI at King's local website for up-to-date news.

2. Scientific goals

The mission statement for the UK DRI at King's is; Defeating Dementia: Understanding disease mechanisms to design smarter diagnostics and effective treatments.

Research programmes are initially focused on investigations into amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer’s disease (AD) to identify the distinct and distinguishing features of different dementias, and then study the etiologic mechanisms at the atomic, molecular, cellular and organism levels. This will aid the design of disease relevant early-stage diagnostics and pave the way for effective therapeutics.   

The centre’s specific goals all belong to the central aim of finding mechanism-based cures for dementia:

  • To understand the structural basis for the formation of protein aggregates (FUS, TDP-43, C9orf72 and Aβ) - decoding this both at the atomic as well at the molecular level – using both biophysical, molecular dynamics simulation and biochemical tools;
  • To identify the cellular basis for aggregate formation and synapse weakening and loss in dementia;
  • To study the consequence of the accumulation of dementia-associated protein aggregates – at the organellar, synapse, cellular and organism function levels;
  • To elucidate the identity of the genes associated with familial and sporadic versions of dementia and to study how these genes influence disease mechanisms;
  • To innovate and develop novel tools and technologies for mechanistic investigations;
  • To design and develop novel mechanism-based diagnostics taking into account amyloid-synapse phenotypes;
  • To use both screening-based and rationally designed therapeutic approaches for reducing amyloid burden, stabilizing synapses, and targeting defective genes.

3. Collaborations

Within UK DRI

  • Prof David Klenerman, UK DRI at Cambridge
  • Prof Bart de Strooper, UK DRI at UCL
  • Prof John Hardy, UK DRI at UCL
  • Prof Adrian Isaacs, UK DRI at UCL
  • Prof Tara Spires-Jones, UK DRI at Edinburgh
  • Dr Mathew Horrocks, UK DRI at Edinburgh


Beyond UK DRI

The UK DRI at King's collaborates extensively within King's and internationally – with both academia and industry alike.

4. Topics

Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease, synapse, protein aggregates.

5. Techniques

Optogenetics, advanced multi-photon live-imaging, DNA-PAINT, FRET-imaging, Super-resolution microscopy (STORM), multiplex longitudinal live cell imaging, phase transitioning, RNA aptamers, NMR, mass spectrometry, Fourier transform infrared spectroscopy, Seahorse technology, circular dichroism, atomic force microscopy, electron microscopy, nanoIR, PET, spectromicroscopy, CRISPR/cas9 screening, iPSC-derived microglia, primary microglia cell culture, CLIP, iPSC cell culture, CRISPR-Trap, RNA-sequencing, single cell sequencing, FUS monoclonal antibodies, AAV DRI Core facility, proteomics, transcriptomics.

6. Scientific Advisory Board

7. Vacancies

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

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8. Meet the team

Annalisa Pastore

Annalisa Pastore

  • UK DRI Group Leader
  • Understanding the role of RNA in the molecular mechanisms of FTD/ALS
  • King's College London
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Chris Shaw

Chris Shaw

  • UK DRI Associate Director
  • Proteostatic mechanisms in FTD and ALS
  • King's College London
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Kei Cho

Kei Cho

  • UK DRI Group Leader
  • Synapse weakening in the pathophysiology of Alzheimer’s disease
  • King's College London
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Lawrence Rajendran

Lawrence Rajendran

  • UK DRI Group Leader
  • Metabolic control of amyloid formation and synapse loss in dementia (molecular amyloidosis & synaptopathy)
  • King's College London
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Marc David Ruepp

Marc-David Ruepp

  • UK DRI Group Leader
  • Altered RNA metabolism in neurodegeneration
  • King's College London
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Sarah Mizielinska

Sarah Mizielinska

  • UK DRI Group Leader
  • Single molecule nucleocytoplasmic transport dynamics in FTD/ALS
  • King's College London
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Tanisha Lewis

Tanisha Lewis

  • Centre Manager, UK DRI at King's
  • King's College London
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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