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Cutting-edge precision profiling of specific cell populations using a Laser Capture Microdissection (LCM) system

Lead Research Organisation: UNIVERSITY OF EXETER
Department Name: Institute of Biomed & Clinical Science

Abstract

Laser capture microdissection (LCM) is a method that allows specific populations of cells to be visually identified on a microscope and then cut out with a laser and collected for analysis. There are a wide variety of different applications for the system, for example it could be used to collect a particular cell type in the brain that is affected by disease, and then compare it to unaffected cells that are collected into a different container. The system also can be useful for comparing different regions, for example to isolate a particular structure in the lungs, or to collect a tumour sample and then compare it to neighbouring healthy cells. A wide variety of different sample types can be studied with this microscope, including fresh biopsies, frozen or fixed autopsies, or even cells grown in a dish. The LCM we plan to purchase is the Leica LMD6, which is contact and therefore contamination free, as a laser is used for cutting and the sample is then collected via gravity. The laser in the system is fast, accurate, maintenance-free, long-life and is adjustable by the user so that can collect many different types of samples. One exciting feature of the LMD6 system is that it has an Auto Detection Mode (ADM), where the user draws around the cells of interest on the screen, and then the software uses this as a template to cut across the rest of the sample, which saves a lot of time and means more sample can be collected. This would be the only LCM in the South West with automated software, meaning it can attract usage from external users as well as the large number of researchers at the University of Exeter who already plan to use the machine. At the University of Exeter, we currently have 17 group leaders, representing in total 46 researchers, who plan to use the system when installed. This includes researchers interested in lots of areas of human health and disease, including brain disorders, lung disease, diabetes, infection, cancer, development and ageing. The LCM will be located in a state-of-the-art building, which is a partnership between the University of Exeter and the Royal Devon and Exeter (RD&E) NHS Trust campus. As this building is home to a Clinical Research Facility (CRF) and a BioResource Centre, there is likely to also be interest in the equipment from clinical teams in the NHS.

Technical Summary

Laser capture microdissection (LCM) is a microscope attached to a laser where, following a rapid staining protocol, it is possible to draw around specific cells of interest, or specific areas of a tissue and collect this for downstream analysis. The system has been widely used for studying the molecular profile of specific cells in heterogenous tissues, or for example to compare a region of pathology to healthy neighbouring tissue. The LCM we plan to acquire is the Leica LMD6. It is contact and contamination free as a laser is used for cutting and gravity for collection. The lasers in this system are guided via optics to allow high cutting speed and precision for cutting the correct area. The laser in the system is maintenance-free, long-life and adjustable by the user so that many different types of samples can be collected. The system can be used for many sample types, including frozen, fresh and fixed tissue, as well as live cells in culture that can then be re-cultivated. One exciting feature of the LMD6 system is the Auto Detection Mode, where the user selects cells of interest in the field of view, and then the system uses this as a template to cut across the rest of the sample, which saves considerable processing time. This would be the only LCM in the South West with automated software, meaning it can attract usage from external collaborators as well as internal users. At the University of Exeter, we currently have 17 principal investigators, representing 46 researchers, who plan to use the system. This includes researchers interested in several areas under the MRC's remit, including brain disorders, lung disease, diabetes, infection, cancer, embryogenesis, development and ageing. The LCM will be housed in a state-of-the-art building, which is a partnership between the University and the RD&E NHS Trust and home to a Clinical Research Facility and BioResource Centre, meaning that there is likely to be interest in the equipment from clinical teams in the NHS.

Publications

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Lunnon K (2025) Epigenomics of AD: a focus on DNA methylation and microRNAs in Alzheimer's & Dementia

 
Description The award of this equipment has allowed us to apply for further funding using it. We were recently awarded a PhD studentship from the Charles Wolfson Charitable Trust, where the student will use this equipment to isolate specific cell types and quantify microRNAs. This project will start in September 2025. Other researchers at the University have applied for funding including the use of this equipment and collaborations on protocols, for example Dr Akshay Bhinge at the University of Exeter will be using LCM in his recent MRC project titled "Dysregulation of RNA processing as a driver of motor neuron dysfunction in Amyotrophic Lateral Sclerosis". We are aware of further grant applications being submitted by Exeter-based researchers and we have worked with these scientists to provide quotes for costs.
Exploitation Route This equipment will be increasingly used over the coming years as grants become funded that have budgeted for the consumables for the equipment.
Sectors Healthcare

 
Description Exploring the role of microRNAs in Dementia with Lewy Bodies
Amount £91,391 (GBP)
Organisation Charles Wolfson Charitable Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2024 
End 09/2027
 
Title High-throughput cell type specific DNA methylation analysis 
Description Three researchers are using the system in combination with ML cell segmentation and classification for high-throughput isolation of cell-types (and phenotypes) of interest, for subsequent DNA-methylation analysis. 
Type Of Material Technology assay or reagent 
Year Produced 2024 
Provided To Others? No  
Impact None yet 
 
Title Optimising Laser-capture microdissection to enable dual rapid staining of neurons expressing synuclein aggregates 
Description We have optimised a protocol from our lab to allow us to rapidly stain neurons bearing synuclein pathology in frozen post-mortem human brain tissue in collaboration with researchers at the University of Cambridge. We are now using this in the project to isolate neurons with and without pathology. This has the advantage over the previous method that we are able to visualise the neurons with antibodies rather than by shape, meaning the separation of cells is more optimal. 
Type Of Material Technology assay or reagent 
Year Produced 2023 
Provided To Others? No  
Impact None yet 
 
Description Collaboration between Maastricht University and the University of Exeter 
Organisation Maastricht University (UM)
Department Maastricht School for Mental Health and Neuroscience (MHeNS)
Country Netherlands 
Sector Academic/University 
PI Contribution Prof Katie Lunnon now has an honorary position at the University of Maastricht whilst similarly Dr Ehsan Pishva now has an honorary position at the University of Exeter. We are in the process of establishing exploring double PhD awards. In the meantime we have several PhD students co-supervised across the two Universities
Collaborator Contribution As a result of the MRC funding we are able to co-supervise students and arrange secondments for their PhDs across the two institutions
Impact Numerous publications (see outputs)
Start Year 2020
 
Description Exeter Bioimaging Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Education session, aimed to highlight the experimental capabilities of RILD. This included a presentation on the LCM and its capabilities to allow more people to utilise the equipment.
Year(s) Of Engagement Activity 2024
 
Description Oral presentation at International Perspectives in Dementia Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Public engagement day held for those living with and caring for those with dementia in and around the Plymouth area.
Year(s) Of Engagement Activity 2023
URL https://www.plymouth.ac.uk/news/university-hosts-dementia-conference