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 Jernej Ule
Centre 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. Adeno-associated Virus (AAV) Platform

Launched by UK DRI at King’s in 2019, the adeno-associated virus (AAV) platform aims to assist with the design and pre-clinical validation and clinical trials of AAV vectors capable of delivering long lasting, cost effective and safe therapies for neurodegenerative diseases.

In recent years there has been a resurgence in gene therapy efforts that is partly fuelled by the identification and understanding of new gene delivery vectors. AAV is a non-enveloped virus that can be engineered to deliver DNA to target cells, and has attracted a significant amount of attention in the field. Prof Chris Shaw, Group Leader from UK DRI at Kings, leads the team in the generation of gene therapy vectors at the UK DRI.

The team are specialists in the production of high-quality AAV, which they apply the Centre’s research into frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). They also advise UK DRI researchers across the Institute on the development, safety and efficacy testing and production of novel AAV tools.

Find out more about the adeno-associated virus platform in the launch news article.


4. Centre Staff

Research, technical and administrative staff that work across lab groups to drive activities at the Centre:

  • Tanisha Lewis (Centre Manager)
  • Imogen Marshall (Centre Administrator)
  • Jordan Guthrie (Laboratory Manager)

5. 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
  • Prof Corinne Houart, UK DRI Associate Member, King's
  • Prof Sandrine Thuret, UK DRI Associate Member, King's

UK DRI Co-investigator

Beyond UK DRI

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

6. Scientific Advisory Board

7. 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.

8. Vacancies

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


9. Meet the team

Andrea Serio

Andrea Serio

  • UK DRI Group Leader
  • Engineering neuroscience to learn more about neurodegeneration
  • King's College London, Amyotrophic Lateral Sclerosis (ALS) research at UK DRI
Read more
Chris Shaw

Chris Shaw

  • UK DRI Group Leader
  • Proteostatic mechanisms in FTD and ALS
  • King's College London, Amyotrophic Lateral Sclerosis (ALS) research at UK DRI
Read more
Emma Clayton

Emma Clayton

  • UK DRI Emerging Leader
  • Synaptopathy in FTD/ALS- investigating presynaptic proteostasis using novel tools in novel models
  • King's College London, Amyotrophic Lateral Sclerosis (ALS) research at UK DRI
Read more
Jernej Ule 1

Jernej Ule

  • UK DRI Centre Director
  • RNA networks in ALS/FTD
  • King's College London, Amyotrophic Lateral Sclerosis (ALS) research at UK DRI
Read more
Marc David Ruepp

Marc-David Ruepp

  • UK DRI Group Leader
  • Altered RNA metabolism in neurodegeneration
  • King's College London, Amyotrophic Lateral Sclerosis (ALS) research at UK DRI
Read more
Sarah Marzi Portrait Web 2

Sarah Marzi

  • UK DRI Group Leader
  • Epigenetic regulation of environmental and genetic risk in neurodegenerative disease
  • King's College London, Amyotrophic Lateral Sclerosis (ALS) research at UK DRI
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Sarah Mizielinska

Sarah Mizielinska

  • UK DRI Group Leader
  • Single molecule nucleocytoplasmic transport dynamics in FTD/ALS
  • King's College London, Amyotrophic Lateral Sclerosis (ALS) research at UK DRI
Read more
Tanisha Lewis

Tanisha Lewis

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