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Regional Provision of Nanostring CosMx Spatial Molecular Imager

Lead Research Organisation: University of Birmingham
Department Name: Institute of Inflammation and Ageing

Abstract

This grant will fund cutting-edge imaging equipment allowing scientists to visualise our body's tissues in unprecedented detail in health and disease. This will enable them to simultaneously determine the levels, location, and function of crucial cell types, receptors and processes, and understand how they interact.

Recent advances in technology - "single cell sequencing" - have allowed doctors and scientists to extract cells from tissue samples and determine which genes are switched on in each individual cell. This has been hugely informative and has changed our understanding of disease. However the data this approach provides is akin to knowing the name and role of every member of the two teams in a football match, but only being allowed to listen to the game on the radio. The new equipment this grant will fund allows us to watch the whole football game as if live: We can actually see the genes switched on in cells in extraordinary detail in the tissues themselves, allowing us to understand how different types of cell communicate with one another in local neighbourhoods to drive processes such as inflammation, cancer and ageing. The ongoing COVID-19 pandemic, which affects multiple tissues in the body, has highlighted the importance of understanding these issues at a fundamental level.

We will place this new equipment in a specialist facility in the University of Birmingham that is dedicated to the study of tissue, and has multiple machines and resources that provide additional complementary data for tissue studies, alongside specialist trained staff. This will ensure that the research enabled by this new equipment will be delivered rapidly, and will be available to the largest possible number of researchers in order to make the greatest possible advances in science and medicine.

Technical Summary

This bid will establish subcellular resolution spatial transcriptomics as a key technology within the University of Birmingham's Birmingham Tissue Analytics Facility [BTA]. The Nanostring CosMx Spatial Molecular imager provides a unique route to characterise diverse tissue microenvironments at single-cell resolution, yielding critical information about cellular phenotypes, differentiation, localisation/trafficking, inter-cellular interactions, and ultimately effector and regulatory mechanisms. Local MRC remit research encompasses discovery, translation, novel therapies and molecular stratification across healthy, diseased and ageing tissue-based research, but crucially we will offer CosMx externally, creating regional provision for this new technology. High resolution spatial transcriptomics capability will greatly complement synergistic digital histology equipment in BTA, one of the only global facilities to combine field-leading multiplex IF and spatial transcriptomics platforms in one integrated vision. Such parallel technologies will catalyse new pipelines integrating spatial transcriptomics and proteomics datasets for rapid analysis, taking advantage of CosMx's linked cloud analysis platform and the strength of the Birmingham Environment for Academic Research (BEAR) computing resource. Our strong emphasis on computational approaches exploits a combination of sophisticated image analysis software platforms and cutting-edge method development working across regional consortia such as COMPARE, maximising biological insights and catalysing interactions between computational and functional biologists.
 
Description Defining the Cellular Basis of Disease Persistence in Juvenile Idiopathic Arthritis
Amount £299,115 (GBP)
Funding ID 22710 
Organisation Arthritis UK 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2021 
End 09/2024
 
Description MICA: BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (the BIO-FLARE study)
Amount £2,849,227 (GBP)
Funding ID MR/N026977/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 12/2023
 
Description NIHR Birmingham Biomedical Research Centre (BRC)
Amount £30,700,000 (GBP)
Organisation National Institute for Health and Care Research 
Sector Public
Country United Kingdom
Start 12/2022 
End 12/2027
 
Description REmission induction of Arthritis caused by Cancer ImmunoTherapy (REACT): a randomised multicentre trial to guide initial therapy for checkpoint inhibitor (CPI) induced arthritis
Amount £1,011,583 (GBP)
Funding ID NIHR154840 
Organisation National Institute for Health and Care Research 
Sector Public
Country United Kingdom
Start 08/2023 
End 08/2028
 
Description REsolving Seronegative and CheckpOint inhibitor-induced iNflammatory ArthriTis by synovial dEconstruction (RESONATE)
Amount £568,174 (GBP)
Funding ID MR/X02914X/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2023 
End 02/2025
 
Description Remission induction of arthritis caused by cancer immunotherapy [REACT]: a randomised multicentre trial to guide initial therapy for checkpoint inhibitor [CPI] induced arthritis
Amount £943,447 (GBP)
Funding ID NIHR 154840 
Organisation National Institute for Health and Care Research 
Sector Public
Country United Kingdom
Start 08/2023 
End 08/2028
 
Description Therapeutic targeting of fibroblast subsets in inflammatory arthritis
Amount £2,034,912 (GBP)
Funding ID MR/S025308/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2019 
End 08/2024
 
Description Tissue research in childhood inflammatory arthritis (TRICIA consortium)
Amount £1,087,871 (GBP)
Funding ID MR/W028557/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2022 
End 11/2027
 
Description JNJ cartography consortium 
Organisation Johnson & Johnson
Department Johnson & Johnson Innovation (JJDC)
Country United States 
Sector Private 
PI Contribution CosMx SMI platform used to provide spatial transcriptomics data for cartography consortium
Collaborator Contribution collaborative analysis and merging of CosMx data with scRNAseq data
Impact doi: https://doi.org/10.1101/2023.03.11.532085
Start Year 2023
 
Description JNJ cartography consortium 
Organisation University of Oxford
Department Kennedy Institute of Rheumatology
Country United Kingdom 
Sector Academic/University 
PI Contribution CosMx SMI platform used to provide spatial transcriptomics data for cartography consortium
Collaborator Contribution collaborative analysis and merging of CosMx data with scRNAseq data
Impact doi: https://doi.org/10.1101/2023.03.11.532085
Start Year 2023
 
Description MICA: Targeting the RA synovial fibroblast via cyclin dependent kinase inhibition - a phase IIa study 
Organisation Cyclacel Ltd
Country United Kingdom 
Sector Private 
PI Contribution development of Phase IIa protocol
Collaborator Contribution development of Phase IIa protocol
Impact MRC DPFS funding
Start Year 2013
 
Description MICA: Targeting the RA synovial fibroblast via cyclin dependent kinase inhibition - a phase IIa study 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution development of Phase IIa protocol
Collaborator Contribution development of Phase IIa protocol
Impact MRC DPFS funding
Start Year 2013
 
Description MICA: Targeting the RA synovial fibroblast via cyclin dependent kinase inhibition - a phase IIa study 
Organisation University of Newcastle
Country Australia 
Sector Academic/University 
PI Contribution development of Phase IIa protocol
Collaborator Contribution development of Phase IIa protocol
Impact MRC DPFS funding
Start Year 2013
 
Description US guided biopsy training: international 
Organisation Brigham and Women's Hospital
Country United States 
Sector Hospitals 
PI Contribution we have contributed to teaching of US guided biopsy to units in the US-wide NIH AMP consortium (alongside QMUL), and also have developed a scientific collaboration with the Boston units We have also trained personnel from other universities, including Gothenberg (Rudin group)
Collaborator Contribution bidirectional collaboration on optimising tissue processing and digestion techniques from biopsies
Impact interim funding for training and protocol development from AMP units. final funding decision awaited.
Start Year 2014
 
Description US guided biopsy training: international 
Organisation North Shore Long Island Jewish Medical Center
Department Feinstein Institute for Medical Research
Country United States 
Sector Academic/University 
PI Contribution we have contributed to teaching of US guided biopsy to units in the US-wide NIH AMP consortium (alongside QMUL), and also have developed a scientific collaboration with the Boston units We have also trained personnel from other universities, including Gothenberg (Rudin group)
Collaborator Contribution bidirectional collaboration on optimising tissue processing and digestion techniques from biopsies
Impact interim funding for training and protocol development from AMP units. final funding decision awaited.
Start Year 2014
 
Description US guided biopsy training: international 
Organisation University of Gothenburg
Country Sweden 
Sector Academic/University 
PI Contribution we have contributed to teaching of US guided biopsy to units in the US-wide NIH AMP consortium (alongside QMUL), and also have developed a scientific collaboration with the Boston units We have also trained personnel from other universities, including Gothenberg (Rudin group)
Collaborator Contribution bidirectional collaboration on optimising tissue processing and digestion techniques from biopsies
Impact interim funding for training and protocol development from AMP units. final funding decision awaited.
Start Year 2014
 
Description online seminar in national Computational Pathology Interest Group 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact invited talk showcasing Birmingham Tissue Analytics facility
Year(s) Of Engagement Activity 2023
 
Description website release 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact web publication about APIPPRA clinical trial
https://www.birminghambrc.nihr.ac.uk/clinical-trial-shows-rheumatoid-arthritis-drug-could-prevent-disease/
Year(s) Of Engagement Activity 2024
URL https://www.birminghambrc.nihr.ac.uk/clinical-trial-shows-rheumatoid-arthritis-drug-could-prevent-di...