Modelling microglia, wearable devices and tau: fifth round of pilot awards announced

Microglia Shutterstock Juan Gaertner

In the spring of this year, we were pleased to announce the eight awardees in the fifth round of the UK DRI Pilot Studies programme - an initiative designed to encourage UK DRI early career researchers to consider new and innovative avenues of dementia research and take their next step towards independence.

The scientific review panel were delighted with the quality of applications submitted from across the UK DRI, with project topics ranging from stem cells to smart watches. From a pool of 18 applications, eight outstanding projects were selected by the panel, and each will receive £44k in funding for the one year project.

Congratulations to all the successful awardees in this round of the Pilot Studies programme. It is always exciting to see the fresh perspectives and novel approaches put forward in applications for this award, and we hope this dedicated funding will help the awardees on their path towards independence and leadership. Dr Aoife Kiely, UK DRI Science Review Manager

The eight projects awarded funding in this round of the Pilot Studies programme are as follows:

Communication between neurons in Huntington’s

Dr Alvaro Murillo Bartolome, Postdoctoral Researcher, UK DRI at Cardiff
Project title: Using CRISPR-Cas13 to restore function in Huntington’s disease neurons

Huntington’s is a progressive neurodegenerative disease caused by a mutation in the huntingtin gene, where a segment of the DNA sequence (CAG) is repeated multiple times, resulting in the production of an abnormally long version of the huntingtin protein. Neurons are the most affected cell type. Dr Murillo is investigating whether correcting how neurons communicate to each other may help prevent neurodegeneration in the disease.

Investigating tau dysfunction in mouse brains

Dr Martha Foiani, Postdoctoral Researcher, UK DRI at UCL
Project title: Investigating tau-dependent mechanical stress in the brain

Alzheimer’s disease and frontotemporal dementia are characterised by a build-up of the protein tau in the brain, which leads to the death of neurons. However, it is not clear exactly how tau accumulation is toxic for the brain. In this project, Dr Foiani will use novel mouse models to study what physical changes occur in the brain when tau becomes dysfunctional.

Improving microglia stem cell models

Dr Hazel Hall-Roberts, Postdoctoral Researcher, UK DRI at Cardiff
Project title: Establishing an in vitro iPSC-microglia model with improved biological age

Microglia, the brain’s resident immune cells, have an important role in several brain diseases, including Alzheimer’s. Induced pluripotent stem cells (iPSCs) can be used to study microglia in the lab, as they have the ability to convert into any cell type. However, iPSC-microglia-like cells seem to remain immature and do not replicate the adult state when grown in isolation. In this project, Dr Hall-Roberts aims to investigate how to make these cells more adult-like, so they are a more authentic model for late-life brain disease.

Tau and mitochondria in Alzheimer’s

Dr Stephanie Fowler, Senior Postdoctoral Researcher, UK DRI at UCL
Project title: Is mitochondrial dysfunction in Alzheimer’s disease associated with mis-localised tau on or within cellular mitochondria?

Mitochondria are the energy powerhouses of the cell, and their health is crucial to cellular health. In many neurodegenerative diseases, mitochondrial defects are one of the first indicators of disease, and often manifest decades prior to the development of dementia. Dr Fowler’s project aims to explore the localisation of tau to mitochondria in cellular models of Alzheimer’s, with a view to furthering understanding of how misfolded tau affects cell function.

Man Wearing Smart Watch Shutterstock Pixel Shot

Round the clock monitoring for uninterrupted care

Dr Kiran Kumar Guruswamy Ravindran, Postdoctoral Researcher, UK DRI Care Research & Technology
Project title: Developing Tools for Round-the-Clock Monitoring of Sleep and Vital Signs in Community Dwelling Older Adults Using High Sampling Rate Inertial Measurement Units

To provide effective care to people living with dementia, there is a need for technology that is cost-effective, scalable, and can provide reliable round-the-clock monitoring of sleep, vital signs and behaviour. Current monitoring technologies such as wearable smart watches and contactless devices have limitations that render them unsuitable for use at a population level. In this project, Dr Ravindran aims to develop robust methods and tools that will allow the use of off-the-shelf high sampling rate accelerometers to record vital signs, track activities and identify novel signatures related to sleep.

Predicting dementia risk using medical records

Dr Samaneh Kouchaki, Academic, UK DRI Care Research & Technology
Project title: A feasibility study to evaluate the use of electronic healthcare records for dementia screening

Emerging interventions such as lecanemab for Alzheimer’s are most beneficial if used at an early stage of the disease. However, early detection is difficult using current diagnosis methods. Healthcare information datasets are now routinely collected during visits to primary and secondary care providers. These contain helpful information, which research has shown could potentially detect dementia. However, manual screening is typically unable to handle data for dementia screening due to the volume and complexity of records and shortage of healthcare professionals. This project by Dr Kouchaki will provide a feasibility study by exploring medical records and building machine learning tools to predict the risk of dementia.

Understanding the effects of reduced blood supply in Alzheimer’s

Dr Juraj Koudelka, Research Fellow, UK DRI at Edinburgh
Project title: Examining the effect of astrocytic calcium dysregulation on vascular haemodynamics relevant to early Alzheimer’s disease

Reduced blood supply in the brain occurs early in Alzheimer’s disease and may be responsible for triggering cell death and memory impairment. Blood supply to meet the energy requirement of cells is regulated by a system called neurovascular coupling. A neuron sends a signal to its supporting cell, the astrocyte, to control the dilation and constriction of blood vessels to regulate the amount of blood supply. However, whilst we know that this process is affected in Alzheimer’s disease, the relationship between signals from astrocytes and blood vessels is not well understood. Dr Koudelka’s project will study these processes in a model of Alzheimer’s disease, visualizing astrocytes live and their signals to blood vessels in awake mice, to better understand the early mechanisms of Alzheimer’s disease and allow new drug targets to be identified.

Investigating the effects of genetic causes of ALS/FTD on cellular processes

Dr Seoungjun Lee, Postdoctoral Researcher, UK DRI at King’s
Project title: Therapeutic testing on nucleocytoplasmic transport dynamics for DPR-induced C9orf72 FTD/ALS neurotoxicity using super-resolution microscopy

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders that share overlapping genetic causes and pathologies, frequently caused by mutations in the C9orf72 gene. These mutations cause issues in transporting material inside cells, which disrupts cellular homeostasis, the process that keeps conditions stable within cells. In this project, Dr Lee will investigate the effects of C9orf72 mutations on these cellular functions, to inform future development of therapeutics.

Congratulations to the successful awardees, and we look forward to seeing their progress over the next year.

Read previous news stories to find out about the projects selected for the first, second, third and fourth rounds of the pilot awards programme. UK DRI researchers can stay updated on calls and deadlines for funding rounds via the UK DRI Portal.

Article published: 7 July 2023
Banner image: Shutterstock/Juan Gaertner