Cambridge

UK DRI at The University of Cambridge

"The UK DRI at Cambridge brings together diverse expertise - from biological to physical sciences - to boost our understanding of the earliest stages of neurodegeneration." Prof Giovanna Mallucci
UK DRI Associate Director

1. At a glance

Neurodegenerative diseases are incurable conditions that primarily affect neurons, the building blocks of the nervous system. When these cells become damaged or die, they can’t be replaced by the body, causing debilitating symptoms – such as movement difficulties and dementia – that will get worse over time. Examples include Alzheimer’s, Parkinson’s and Huntington's disease.

Due to an ageing population in the UK, we are expecting an increase in the number of people developing neurodegenerative diseases over the coming decades. But developing new treatments that can prevent the onset of disease or protect neurons from damage is hindered by our lack of knowledge in the fundamental causes and mechanisms behind neurodegeneration.

Scientists at the UK DRI at Cambridge are using cutting-edge approaches to build our understanding of the biological processes behind the earliest stages of neurodegeneration and ageing. For instance, they are exploring mechanisms causing the loss of vital connections between neurons and the pathways that drive repair of these connections - essential for memory formation and survival of brain cells. They are also studying the causes and effects of build-up and spread of misfolded proteins in disease. They have already identified a number of promising targets for testing in patients and hope to identify new key molecular targets that can be translated into effective new treatments that can stop, slow down or reverse dementia.

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

2. Scientific goals

The UK DRI at Cambridge aims to use interdisciplinary, groundbreaking approaches for new mechanistic understanding that will bring new treatments to tackle dementia. The scientific focus is on mechanisms underlying the earliest stages of disease and the ageing process, including repair/protective responses involved in brain plasticity, to yield new targets that will give maximal benefit for therapy and have the greatest potential for prevention of dementia.

To this end, the centre houses several innovative, interdisciplinary research programmes that cover distinct but related aspects of the earliest disease phases. 

These programmes aim to:

  • understand the initial spreading of misfolded proteins (specifically, tau and alpha-synuclein);
  • target the intracellular replication of tau with intrabodies;
  • understand pathways driving synapse loss and enhancing synaptic repair in neurodegeneration;
  • identify novel genes in synapse repair pathways;
  • explore endoplasmic reticulum (ER) dynamics and dysfunction in health and disease;
  • investigate the role of DNA damage pathways in neurodegeneration;
  • gain novel insights into inducing protective responses, including autophagy and other stress responses.

The centre will grow to expand beyond these areas, building on specific domains and on interactions between all programmes, continuing to uphold the principles of cross-disciplinary science and seeking collaborations across the UK DRI to share expertise and pursue synergistic goals.

While an early goal is to generate new scientific understanding and provide new targets for potential therapies, the latter poses major challenges for translation. 

The mission of the centre also involves finding creative ways of overcoming bottlenecks that delay bringing scientific understanding to clinical translation. A strategic aim is to help enable the streamlined delivery of these discoveries into translational research and ultimately clinical trials for new treatments of dementia. 

We have recently established the Gnodde Goldman Sachs Translational Neuroscience Unit, the purpose of which is to accelerate and facilitate translational studies in humans.

3. Collaborations

Within UK DRI

  • Prof Kei Cho, UK DRI at King's
  • Programmes at UK DRI at Cardiff

Beyond UK DRI

4. Topics

Synapses, protein spreading, interdisciplinary research, endoplasmic reticulum, DNA damage, autophagy

5. Techniques

Single particle tracking (SPT) and trajectory analysis, Fluorescence Lifetime Imaging (FLIM), human/mouse haploid ESCs, iN system, conditional protein-degron systems (SMASH-tag), FUCCI cell-cycle analysis system, CRISPR-Cas9 screening, CHIP, Ube2w, DNA paint, pFTAA, primary neuronal cell culture, human iPSCs, chemical kinetics, biophysical methods to image and characterise full-length tau aggregates, super-resolution microscopy, human iPSC-derived cortical and dopamine neurons, zebrafish and mouse models, high content imaging, mass-spectrometry-based immunoprecipitation proteomics

6. Vacancies

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

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7. Meet the team

David Klenerman

David Klenerman

  • UK DRI Group Leader
  • Understanding the molecular basis of tau aggregation and spreading
  • Cambridge
Read more
David Rubinsztein2

David Rubinsztein

  • UK DRI Group Leader
  • Identification of novel pathways that induce autophagy to enable neuroprotection
  • Cambridge
Read more
Edward Avezov

Edward Avezov

  • UK DRI Group Leader
  • Role of ER dynamics and morphological regulation in neuronal health and disease
  • Cambridge
Read more
Emmanouil Metzakopian

Emmanouil Metzakopian

  • UK DRI Group Leader
  • CRISPR-Cas9 genetic screens for novel synaptic maintenance genes and therapeutic targets
  • Cambridge
Read more
Gabriel Balmus2

Gabriel Balmus

  • UK DRI Group Leader
  • Identifying neuroprotective mechanisms against genomic instability accrual in ageing and neurodegeneration
  • Cambridge
Read more
Giovanna Mallucci

Giovanna Mallucci

  • UK DRI Associate Director
  • Driving synaptic repair in early neurodegeneration
  • Cambridge
Read more
Helois Radford Rose

Helois Radford-Rose

  • Centre Manager, UK DRI at Cambridge
  • Cambridge
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Will Mc Ewan

Will McEwan

  • Sir Henry Dale Fellow and UK DRI Group Leader
  • Harnessing immunity to target protein aggregation.
  • Cambridge
Read more

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