"The UK DRI at Imperial brings new perspectives to prevent, delay or reverse dementia. We focus on the earliest stages when benefits to those who may be affected will be greatest." Prof Paul Matthews
UK DRI Centre Director
1. At a glance
People with Alzheimer’s disease (AD) and other types of dementia experience a variety of progressive symptoms – such as memory loss, mental decline and personality changes. So understandably, much of the current research into dementia is focussed on the brain – to explore what leads to the gradual loss of function and death of neurons.
The UK DRI at Imperial brings together researchers from diverse backgrounds with fresh perspectives. They draws on the university’s unique strengths, resources and focus on science, engineering, medicine and business. The team recognises that the challenges of dementia demand new concepts, new approaches and a diverse range of new research tools and directions. Their holistic approach views the ageing brain in the context of the ageing body, not in isolation. Studies from individual cells through to whole systems are creating a new vision of what can go wrong and lead to dementia. Our multidisciplinary approach brings new expertise to focus on the challenges of dementia research. Investigators are addressing the transition from vulnerability to the expression of neurodegenerative pathology by exploring individual variation across populations, influences of the gut on the brain, mutual interactions between neurons and glia (immune cells) and roles for homeostatic mechanisms of sleep in pathological processes.
The centre aims to identify what goes wrong in the brain at the very earliest stages of dementia and to develop innovative treatments that can correct detrimental changes, which could greatly benefit people who are at increased risk of disease but have not yet developed symptoms – preventing or slowing down the onset of disease.
Visit UK DRI at Imperial's local website for up-to-date news.
2. Scientific goals
The researchers at this centre view the ageing brain in the context of the ageing body, using approaches that integrate function – from individual cells through to systems and populations. The objectives are translational so that people with dementia and their families realise the benefits from research as rapidly as possible.
The approach starts from the view that most of the major advances in the understanding of dementia have been drawn from the discovery of genetic determinants of susceptibility. However, these contribute only partially to the expression of disease. An additional major component of this is related to the effects of influences arising from - or acting via - the whole body: co-morbid systemic diseases, the environment and lifestyle. The centre is addressing Alzheimer's disease and related dementia as systemic diseases. In an increasingly sub-specialised clinical and research world, this challenges more usual research strategies.
The approach is built around four investigative themes:
- Circadian Neurobiology
- Metabolomics and Microbiome
- Microcircuits and Brain Systems
The team includes complementary expertise that together have a unique potential to address these questions. It has a critical mass of internationally leading investigators in metabolomics, the microbiome and molecular neuroepidemiology. They have developed, or contribute to, large population studies that provide access to the detailed linkage of the genetic and detailed clinical and lifestyle data of people before they develop dementia.
Other investigators have been leaders in fundamental and clinical investigations of multiple sclerosis, arguably the “paradigmatic” neuroinflammatory, neurodegenerative disorder. The expertise in circadian neurobiology promises to discover novel mechanisms by which altered sleep patterns enhance neuronal stress and accelerate neurodegeneration. Outputs from these programmes together can then be focused on how brain microcircuits become dysfunctional in the early disease and how their associated neuronal systems can be therapeutically modulated bioelectronically.
3. Multi-‘omics Atlas Project (MAP)
Launched in March 2020, the Multi-‘omics Atlas Project (MAP) is a £2M Directors’ initiative led by UK DRI at Imperial, which aims to create an ‘atlas’ of the brain at different stages of Alzheimer’s disease. It is the first time that UK brain tissue resources have been coordinated on such a scale to study Alzheimer’s disease pathology at every stage of the illness, and is set to rapidly improve our understanding of the processes that lead to people developing the illness.
The project is managed by Senior Scientific Project Manager, Dr Johanna Jackson, under the leadership of Centre Director, Prof Paul Matthews. The team use an unprecedented range of advanced techniques to examine tissue from eight different regions of the brain. The aim is to gain a much fuller understanding of key cell characteristics, including what influences the genes of individual cells to be expressed, and the role of proteins and other factors on their function. The data obtained is combined with information gathered from microscopic examination of the tissue, and with the medical history of each brain donor. Powerful new molecular imaging technology are used to examine subtle but important differences in cell types and their relationships in the brain. From these data, scientists are able to develop a better understanding of how individual cells function and interact with their environment.
4. Centre Staff
Research, technical and administrative staff that work across lab groups to drive activities at the Centre:
- Dr Jennifer Podesta (Centre Manager)
- Megan Winterbotham (Laboratory Manager)
- Lauren Troy (Project Officer)
- Josh Beale (Project Officer)
- Shamara Lowe (Section Manager)
- Dr Diana Benitez (Project Coordinator)
- Jia Du (iPS Cell Culture Technician)
- Siobhan Dillon (PA to Prof Paul Matthews)
- Dr Nazanin Doostdar (Laboratory Manager)
Within UK DRI
- Prof Julie Williams, UK DRI at Cardiff
- Dr Gaynor Ann Smith, UK DRI at Cardiff
- Dr Owen Peters, UK DRI at Cardiff
- Prof Caleb Webber, UK DRI at Cardiff
- Prof Giles Hardingham, UK DRI at Edinburgh
- Prof Bart De Strooper, UK DRI at UCL
- Dr Carlo Frigerio, UK DRI at UCL
- Prof John Hardy, UK DRI at UCL
- Prof Joanna Wardlaw, UK DRI at UCL
UK DRI Co-investigator
- Prof Jules Griffin, Imperial College London
Beyond UK DRI
The UK DRI at Imperial creates a broad range of opportunities to reach out to world-leading research groups across Imperial College London, including the:
- MRC London Institute for Medical Sciences
- Imperial College Centre for Synthetic Biology
- MRC-PHE Centre for Environment and Health
- EPSRC Centre for Mathematics of Precision Healthcare
The centre’s integration with the NIHR Imperial Biomedical Research Centre (BRC) Brain Sciences Theme is also facilitating collaboration with clinical science in this area.
The Parkinson’s UK and Multiple Sclerosis Society Tissue Banks hosted by Imperial College London are part of the MRC UK Brain Banks Network.
6. Scientific Advisory Board
- Dr Des Walsh, Imperial College London (chair)
- Prof Judith Frydman, Stanford
- Prof Stéphanie Lacour, EPFL
- Dr Guy Rouleau, Neuro
- Prof Erin Schuman, Max Planck Institute
- Prof Maria-Elena Torres-Padilla, Helmholtz Munich
Imaging Mass Cytometry, CyToF technology, FACS, 3D cell culture, multi-electrode arrays, vivo 2-P imaging of calcium activity, slice electrophysiology and Patch-seq, non-invasive bioelectronic stimulation (temporal interference stimulation), AAV and mouse models, virally-delivered FosTRAP technology, proton nuclear magnetic resonance (1H NMR) spectrometry, ultra-performance liquid chromatography (UPLC)-mass spectrometry (MS), EEG, fMRI, temporal interference (TI) stimulation, finite element method (FEM), modelling, in vivo patch-clamp recording, metabolomics, computational modelling, spectral profiling techniques, next-generation sequencing, DESI imaging, scRNASeq, ATACSeq and IF proteomic mass spectromic characterisation, PET scanning, snRNAseq, high field and ultra high field MRI functional mapping, tether-free EEG recordings and analysis of sleep-wake patterns, c-fos-dependent activity-tagging (also known as TetTagging), automated sleep deprivation protocols; in vitro and in vivo optogenetic and pharmacogenetic stimulation of tagged circuitry; behavioural analysis; brain slice electrophysiology; in vivo dialysis.