Advances in technology help drive scientific discoveries. To enable researchers to investigate neurodegeneration and dementia in new ways, the UK DRI has established the ‘Proteomics’ and ‘Single Cell and Spatial Transcriptomics’ technology platforms. These provide researchers with access to specialist equipment for studying protein and gene expression patterns at an unprecedented level of detail.
Matching expertise and interests
Dr Sam Jackson, Tools and Technology Platform Manager at the UK DRI, led the initial workshops on proteomics and single cell/spatial transcriptomics in November 2020 and April 2021, respectively. These brought experts together with UK DRI researchers for a series of talks and discussions to understand how the different technologies could be applied to neurodegeneration research. Following these successful meetings, we have launched funding competitions which aim to provide researchers with the resources to perform pilot experiments with the technologies. For Proteomics, we are pleased to have funded eight projects with four fantastic external collaborators from the University of Dundee, the University of Manchester and Imperial College London. Recently, we’ve also invested in 11 projects involving Single Cell and Spatial Transcriptomics, which will begin in the coming months.
The power of the new platforms
Due to the nature of the techniques, the large datasets generated have the potential to be analysed in distinct ways to answer several different scientific questions from multiple labs. Researchers will benefit from the platforms with access to specialist techniques, as well as the detailed datasets created, greatly expanding the experimental possibilities. Find out more about the new platforms and projects funded below.
funded by the technology platforms
UK DRI technology platforms provide researchers with access to cutting-edge analytical techniques to study neurodegeneration, allowing samples to be analysed in unprecedented detail. The knowledge generated will ultimately feed the pipeline for new dementia treatments.Dr Sam JacksonUK DRI Tools and Technology Platform Manager
Proteomics Platform: collaborating with mass spectrometry experts
Proteomics is the study of the composition of proteins in cells and tissues. Since proteins are responsible for many of the functions of cells, proteomics can give an insight into molecular processes and their regulation. Identifying the proteins in tissues, either in total or in a particular protein subset, requires machines called mass spectrometers. These pieces of scientific equipment are expensive and require specialist knowledge to operate, so are not readily available to most labs.
The Proteomics Platform aims to overcome these challenges by establishing collaborations with UK-based mass spectrometry experts. These labs will perform the techniques on samples from UK DRI researchers, who otherwise would not be able to perform mass spectrometry-based proteomics analyses. Two labs at the University of Dundee are part of this research partnership: Prof Dario Alessi, at the MRC Protein Phosphorylation Unit (MRC-PPU), and Douglas Lamont, at the FingerPrints Proteomics Facility. In addition to cutting-edge instruments, these labs have decades of experience at applying mass spectrometry to biological samples, so are ideal partners for the UK DRI in proteomics. Dr Bethany Geary, experienced with mass spectrometry and a bioinformatics expert, will be the lead scientist responsible for the management of the Proteomics Platform. Collaborations have also been established with other UK-based mass spectrometry experts to increase the variety of proteomics specialisms available.
Prof Dario Alessi, Director of the MRC-PPU at the University of Dundee, said:
“We are delighted to have the opportunity to collaborate and offer UK DRI researchers access to our MRC-PPU Units mass spectrometry platforms. Mass spectrometry is the go-to method to study how disease processes, mutations, inhibitors and other perturbations impact protein expression and post-translational modification, and it can provide important molecular insights of relevance to better understand neurodegenerative diseases.”
Dr Megan Torvell (UK DRI at Cardiff) is an early career researcher who has been awarded funding from the Proteomics Platform to investigate regional and progressive protein changes in a mouse model of Alzheimer’s disease in collaboration with proteomics expert Dr Richard Unwin (University of Manchester). This project will seek to help answer why some brain regions undergo neurodegeneration during Alzheimer’s disease, while others are spared.
Speaking on the aims of this proteomics study and how it will benefit her as an early career researcher, Dr Torvell said:
“This project will identify early pathway perturbations, which will point towards potentially reversible targets. The data generated here will provide a strong evidence base and clear rationale for future studies and, in doing so, will be pivotal for my career progression as I apply for fellowships and transition to independence.”
The full list of researchers that have been awarded funding through the Proteomics Platform, and their proteomics collaborators, are:
Identifying protective proteomics changes in frontotemporal dementia/ amyotrophic lateral sclerosis: Prof Adrian Isaacs (UK DRI at UCL) in collaboration with Prof Dario Alessi (MRC-PPU at the University of Dundee)
Identifying microglial proteins that modulate disease-associated cell states: Dr Alexi Nott (UK DRI at Imperial) in collaboration with Dr Harry Whitwell (Imperial)
Discovering brain cell proteome changes during mouse aging: Dr Blanca Díaz-Castro (UK DRI at Edinburgh) in collaboration with Prof Dario Alessi (MRC-PPU at the University of Dundee)
Developing a high throughput proteomic assay for dementia research: Dr Brenan Durainayagam (UK DRI at Imperial) in collaboration with Dr Harry Whitwell (Imperial)
Single-cell proteomics profiling of vulnerable neurons in Alzheimer’s disease: Dr Martha Foiani (UK DRI at UCL) in collaboration with Prof Dario Alessi (MRC-PPU at the University of Dundee)
Determining protein expression changes in a mouse model of Alzheimer’s disease: Dr Megan Torvell (UK DRI at Cardiff) in collaboration with Dr Richard Unwin (University of Manchester)
Identifying synaptic targets of complement: Dr Soyon Hong (UK DRI at UCL) in collaboration with Prof Dario Alessi (MRC-PPU at the University of Dundee)
Studying pathological tau filaments through proteomic analysis: Dr Taxiarchis Katsinelos (UK DRI at Cambridge) in collaboration with Douglas Lamont (FingerPrints Proteomics Facility)
Single Cell and Spatial Transcriptomics Platform
Transcriptomics involves studying the mRNA content of cells to determine gene expression patterns. While some techniques involve the measurement of mRNA from all the cells in a tissue, single cell transcriptomics determines the gene expression of individual cells. This is especially useful for distinguishing expression patterns between multiple cell types in the same tissue. Furthermore, spatial transcriptomics enables researchers to identify the exact location in the tissue where different genes are expressed. This spatial resolution means that gene expression patterns can be related to specific parts of the tissue, giving more detailed mechanistic insights into cell functions and neurodegeneration.
The Single Cell and Spatial Transcriptomics Platform aims to increase the availability of these techniques to researchers, installing machines at several labs across the Institute. In time, these labs will provide a service for other labs, helping others harness the power of single cell and spatial transcriptomics for their projects.
The full list of researchers that have been awarded funding through the Single Cell and Spatial Transcriptomics platform are:
Investigating the mechanism of astrocyte dysfunction during Parkinson’s disease: Zongze Li (UK DRI at Cardiff)
Epigenetic profiling of the human brain: Dr Di Hu (UK DRI at Imperial)
Profiling the gene expression of dysfunctional neurons: Dr Michael Morten and Dr Carola-Izabela Radulescu (UK DRI at Imperial)
Defining microglial responses to necrotic brain tissue: Dr Jack Barrington (UK DRI at Edinburgh)
Investigating variability in microglia that result from protein dysfunction: Michael Sewell (UK DRI at Edinburgh)
Investigating the response of brain cells to brain modulation: Gerard Crowley (UK DRI at UCL)
Identifying disrupted transcriptomic profiles in frontotemporal dementia: Dr Niamh O’Brien (UK DRI at King’s)
Investigating the role of microglia in frontotemporal dementia/amyotrophic lateral sclerosis: Prof Adrian Isaacs (UK DRI at UCL)
Enhancing transcriptomic analysis in human brains with dementia: Melissa Leija Salazar (UK DRI at UCL)
Investigating inflammatory microglia and astrocytes in an Alzheimer’s disease mouse model: Dr Ruth Jones (UK DRI at Cardiff)
Assessing microglia in different brain regions during cerebrovascular-mediated brain injury and cognitive decline: Dr Stefan Szymkowiak (UK DRI at Edinburgh)
Article published: 17 September 2021
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