New UK DRI scheme launched to fund bold and boundary pushing research

Rna Sshutterstock Kateryna Kon

As the UK’s leading national institute for neurodegenerative disease research, the UK DRI is well positioned to tackle some of dementia’s most pertinent research questions that will lead to breakthrough discoveries. Today, we are delighted to announce the first recipients of the new ‘Key Questions’ intramural funding programme, leveraging the unique strengths and capabilities of our Institute to catalyse bold and ambitious research projects, which adopt multidisciplinary and innovative approaches.

As part of the Institute’s strategy to leverage intramural funding opportunities to push the boundaries of dementia and neurodegenerative research, this scheme particularly welcomed projects which incorporated higher risk components, not necessarily suitable for conventional external funding schemes.

From a pool of 24 applications, eight outstanding projects were selected for Stage I of the programme, which will provide pump-priming funding of up to £150K for one year. Successful awardees will give updates after nine months, and subject to progress will be invited to apply for the second stage of the programme, where up to an additional £1M may be awarded for up to three years.

The international panel of expert reviewers were particularly impressed with the calibre and diversity of projects submitted from across the Institute, ranging in subject from synapses to sleep.

I am delighted to announce this new funding programme, which underscores our commitment to pushing the boundaries of dementia and neurodegenerative research by supporting bold and innovative projects which tackle the most pressing unanswered questions in the field. I would like to congratulate the recipients of the Stage I funding. Prof Siddharthan Chandran, UK DRI Director

The eight projects awarded funding in Stage I of the Key Questions funding programme are as follows:

New approaches to treating Huntington’s

Prof Gabriel Balmus and Prof Sarah Tabrizi
Project title: Developing protein-protein interaction modulators for stabilising CAG repeat expansions in Huntington's disease

Recent studies have identified specific genes, implicated in the repair of damaged DNA, that may influence disease onset and progression of Huntington’s. In this project, Profs Balmus and Tabrizi aim to modulate these genes in order to develop novel therapeutic interventions for the condition.

How impairments in the brain's internal clock and memory come together in Alzheimer's disease

Dr Marco Brancaccio and Dr Julija Krupic
Project title: Lost in space and (circadian) time: Investigating the role of disrupted deep brain circuitry in diminished spatial memory function in Alzheimer’s disease

Disruption in sleep-wake cycles can occur decades before the hallmark memory symptoms of Alzheimer’s start, but little is known about how impairments in deep brain regions like the hypothalamus – responsible for controlling the body’s internal clock – affect spatial memory and other cognitive processes. This project aims to use animal models to study how Alzheimer’s pathology-related impairments in these deep brain structures affect the hippocampal function to cause memory deficits.

Understanding the role of synapses in resilience to cognitive decline in Alzheimer’s

Dr Patricio Opazo, Dr Owen Dando, Dr Claire Durrant, Dr Johanna Jackson and Dr Natalie Connor-Robson
Project title: Using an all-human approach to identify synaptic signatures of cognitive resilience to Alzheimer’s disease

Although Alzheimer’s is typically triggered by the accumulation of amyloid beta and tau in the brain, about a third of the elderly population have a build up of these misfolded proteins in their brains, without experiencing symptoms of memory loss. This project aims to identify the unique profile of synapses in this group, and investigate their role in maintaining healthy synaptic function in neurons.

Synapse Shutterstock Tatiana Shepeleva

The undetermined role of oligodendrocytes in ageing and Alzheimer’s

Dr Sarah Marzi, Dr Dervis Salih and Dr Alexi Nott
Project title: Identifying genetic and epigenetic drivers of oligodendrocytes in ageing and Alzheimer's disease

Oligodendrocytes are a type of supporting cell in the brain that produce myelin, an insulating layer that forms around neurons, important for transmitting electrical signals between cells in the brain. Research has shown that genes associated with oligodendrocytes can impact Alzheimer’s risk. Dr Marzi and colleagues aim to use genetic studies to investigate the regulation of ageing and Alzheimer’s progression in oligodendrocytes. Understanding genetic and epigenetic changes in oligodendrocytes and myelin with ageing may help to develop sensitive new biomarkers to predict dementia, and could lead to the development of new therapeutic targets.

Investigating subtle sleep changes in Alzheimer’s

Dr Marc Aurel Busche and Dr Jian Gan
Project title: Pioneering an AI-driven framework to decode and enhance memory during sleep in ageing and Alzheimer’s disease

Sleep is critical for healthy brain function. In the early stages of Alzheimer’s, before major disruptions in sleep patterns become apparent, subtle sleep-related changes may already be contributing to memory and cognitive problems. In this collaborative project, the scientists will develop a novel artificial intelligence (AI) -inspired approach to study memory reactivations during sleep in mouse models and humans, in order to identify impairments during ageing and early Alzheimer’s.

Sleep Shutterstock Michaeljung

RNA splicing and its role in Parkinson’s

Prof Mina Ryten, Prof Sir John Hardy and Prof Sonia Gandhi
Project title: Investigating the role of pre-mRNA mis-splicing as a driving mechanism in Parkinson's disease

RNA, the building block which forms a template for the production of proteins within our bodies, needs to be cut, or ‘spliced’ during its production, to ensure the correct parts are used to form each protein. This process is known to be disrupted in some neurodegenerative diseases, but it is not known whether this is the case for Parkinson’s. In this project, Prof Ryten and Prof Hardy aim to determine whether RNA splicing has a role in the development or progression of Parkinson’s.

Developing new cell models to study Alzheimer’s

Prof Sir David Klenerman, Prof Bart De Strooper and Prof Selina Wray
Project title: Development of a robust cellular model for late onset Alzheimer's disease to elucidate disease mechanisms

How the formation of amyloid beta plaques and tau tangles lead to cell death in Alzheimer’s is not yet well understood. Furthermore, almost all prior research using animal or cell models uses systems based on early onset genetic causes of Alzheimer’s, despite the fact that 95% of cases are sporadic and cannot be tied to a single genetic cause. This project aims to address these issues, by developing reliable cellular models of late onset Alzheimer’s, to uncover the mechanisms of the disease.

New models to examine the role of TDP-43 protein in ALS

Dr Sarah Mizielinska, Dr Bhuvaneish Selvaraj, Dr Marc-David Ruepp and Prof Adrian Isaacs
Project title: Dissecting the molecular determinants of TDP-43 targeting for ALS/FTD

For the majority of people affected by amyotrophic lateral sclerosis (ALS), a protein known as TDP-43 is incorrectly located within their cells, causing essential processes in cells to stop working normally. In this project, the team aim to develop cellular models to examine how the mislocalisation of TDP-43 contributes to the death of motor neurons in ALS.

Find out more about these projects in the coming weeks by staying tuned to our social media channels, and sign up to receive our monthly newsletter for updates.

Article published: 3 May 2024
Images: Shutterstock: Kateryna Kon, Tatiana Shepeleva, Michael Jung