Manchester Academic Health Science Centre Technology Hub: Clinical Proteomics Centre for Stratified Medicine

Lead Research Organisation: University of Manchester
Department Name: Medical and Human Sciences

Abstract

The genomic and post-genomic age promises much for clinical medicine, as we can now sequence genomes (the blueprint), and measure gene expression fairly routinely and now we can measure the amounts of proteins (the structural and catalytic functional entities in the cell) produced. Yet, to date, the biomedical community have struggled to integrate these technologies and generate the impact anticipated some years ago. The University of Manchester proposes to engage with this challenge by setting up a completely new facility, building on its strengths in biochemistry, to enable clinicians to choose the right treatment for the right patient at the right time. The biochemistry base that will be built, using state of the art technologies, can serve this objective in a number of different ways for a wide range of different diseases. Furthermore, the benefits generated from the facility will be available to researchers from other universities and industrial partners (such as drug companies) to use, with the aim to maximise its impact in diagnostic and translational medicine beyond Manchester.

This new facility will use a new development of mass spectrometry that supports the measurement of many proteins within a sample (such as blood, urine, or from tissue such as a tumour biopsy) within a much shorter time than has ever been possible before. Such techniques will be of huge benefit to clinical researchers as it will allow them to see the differences between samples from, for example, healthy people and people with a specific disease - this will give insights into how that disease develops and, importantly, how it might be treated. In addition, by examining the differences in the levels of particular marker proteins from patients who respond to a drug compared to those who don't respond, doctors will be able to identify which drug is the best treatment for individual patients. This will have economic benefit as drugs will not be used on patients who will receive no benefit from them. We will look in the first instance for such protein markers through the disease course, and treatment response in rheumatoid arthritis, psoriasis and cancer.

Technical Summary

This bid proposes the development of a unique world-leading clinical proteomics centre (CPC) for stratified medicine and mechanistic studies of disease. The objectives for the proposed centre include the pragmatic discovery of novel protein biomarkers to lead to early diagnosis of disease, stratification of patients according to their disease endotype and also according to their therapeutic response to a specific treatment. Additionally, we anticipate the CPC will offer a valuable resource for experimental medicine studies to understand the basis of disease mechanisms. Within the proposed CPC we will apply the very latest in innovative mass spectrometry-based technology on a high capacity throughput, for the first time in the UK. Sequential Window Acquisition of all THeoretical fragment-ion spectra Mass Spectrometry (SWATH MS), combined with Selected Reaction Monitoring (SRM) proteomics techniques will allow the creation of a digitised, quantitative, permanent record of the proteome. Linkage of proteomic data to electronic health records through the Farr@HeRC health informatics centre will be achieved through a secure 'eLab' platform, allowing the integration of complex molecular phenotyping with endotypic data (such as therapeutic outcome and medical history). Exemplar stratified medicine projects will be enabled once CPC is set up, and will include the use of samples from the MRC-funded stratified medicine programmes around psoriasis (PSORT) and rheumatoid arthritis (MATURA), where the digitised proteome can be interrogated alongside other 'omics and clinical data. Additionally, a number of other mechanistic studies around leukaemia and other solid cancers have already been identified and will proceed when the CPC is established. Combined with validation and verification platforms, the facility will offer unparalleled power to discover novel biomarkers and elucidate the underlying pathophysiological mechanisms of disease.

Planned Impact

1) Who will benefit from this research?

- Clinical scientists and experimental medicine researchers
- Clinicians, NHS
- Patients
- Drug discovery/ development groups
- Industry, including big pharma and biotech

2) How will the above groups benefit?

In short, the groups listed above will benefit from a quicker time to clinical validation of biomarkers and the improved prospect of personalised medicine penetration into the clinic with associated economic benefit.

Specifically-
- Clinical scientists and experimental medicine researchers will benefit through being able to access an innovative high capacity resource not currently available elsewhere in the UK, allowing them to undertake discovery biomarker projects and experimental studies in a fraction of the time. The ability to create a permanent digitised record (and subsequently iteratively mine this) will allow precious clinical samples and biobanks to be used sparingly;
- Clinicians and the NHS will benefit through the ultimate development of improved diagnostics and predictors of response, allowing earlier diagnosis and reduction in prescribing errors - all of which will ultimately reduce the necessity of inappropriate or aggressive treatment and, in turn, the economic burden of disease on the health service;
- Patients will benefit through better diagnostics and 'theranostics' by being detected earlier (improving outcome) and, following diagnosis, by being treated right first time;
- Drug discovery and development groups will be able to identify those individuals who are most likely to benefit from the drugs they are developing and allowing them to be targeted appropriately (reducing side effects and non-response);
- Pharma will benefit by being able to access a facility which will allow them to identify novel "druggable" targets through the comparison of proteomic signatures from patients and healthy volunteers, mass spectrometry instrument manufacturers (and specifically AB SCIEX and Waters) will benefit through having their techniques validated and translated into clinical practice (and the potentially larger market share this will bring), smaller biotech will benefit from pharma's increased use of protein or expression based diagnostics and the opportunities this will bring in terms of companion diagnostic development

Publications

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Russell MR (2016) Protein Z: A putative novel biomarker for early detection of ovarian cancer. in International journal of cancer

 
Description MRC Workshop on Methodology for Stratified Medicine - July 2015. 'Stratum Verification'
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Rosalind Franklin Institute Biological Mass Spectrometry
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description UK Biobank Enhancement Working Group
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Biomedical Research Centre
Amount £28,500,000 (GBP)
Organisation University of Leicester 
Department NIHR Biomedical Research Centre
Sector Hospitals
Country United Kingdom
Start 04/2017 
End 03/2021
 
Description MICA: NURTuRE - changing the landscape of renal medicine to foster a unified approach to stratified medicine
Amount £2,561,603 (GBP)
Funding ID MR/R013942/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2018 
End 07/2022
 
Description Molecular Pathology Nodes Call Feb 2015
Amount £2,886,686 (GBP)
Funding ID MR/N00583X/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2015 
End 09/2019
 
Description Research Grant
Amount £604,167 (GBP)
Funding ID MR/N028457/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 04/2016 
End 03/2020
 
Description Research Grant
Amount £324,224 (GBP)
Funding ID BB/P024424/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 12/2017 
End 11/2020
 
Description Small pilot grants
Amount £15,000 (GBP)
Organisation Genesis Breast Cancer Prevention Appeal 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2016 
End 10/2016
 
Description Wellcome Trust Institute Strategic Support Fund (University of Manchester)
Amount £44,500 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2015 
End 09/2016
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation Academia Sinica
Country Taiwan, Province of China 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation Chang Gung University
Country Taiwan, Province of China 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation Chinese Academy of Sciences
Country China 
Sector Public 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation ETH Zurich
Country Switzerland 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation Fudan University
Country China 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation Korea Institute of Science and Technology Information (KISTI)
Country Korea, Republic of 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation Korea University
Country Korea, Republic of 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation Leibniz Association
Department Leibniz Institute for Analytical Sciences
Country Germany 
Sector Charity/Non Profit 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation Lund University
Country Sweden 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation Macquarie University
Country Australia 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation McGill University
Country Canada 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation National Cancer Centre
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation National Cancer Institute (NCI)
Country United States 
Sector Public 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation Shanghai Institute of Materia Medica, China
Country China 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation The Garvan Institute for Medical Research
Country Australia 
Sector Charity/Non Profit 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation University of British Columbia
Country Canada 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description International Cancer Proteogenome Consortium- Cancer Moonshot 
Organisation University of Dundee
Department School of Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Collaborator Contribution International proteomics network for cancer research that is sharing best practice sample processing and mass spectrometry protocols and data from various tumour samples.
Impact Proteomics collaboration, outputs so far include standard operating procedures agreed by consortium.
Start Year 2017
 
Description Stoller/SCIEX research collaboration 
Organisation AB SCIEX
Country United States 
Sector Private 
PI Contribution Stoller staff are providing intellectual input, access to facilities and equipment and will be training PhD students. The goal of the partnership is to industrialise proteomics with appropriate QA/QC measures.
Collaborator Contribution SCIEX staff are providing on site support from field service engineers to maintain the equipment and application chemists advising on use of the instrumentation, training new users and jointly developing new methodologies. The goal of the partnership is to industrialise proteomics with appropriate QA/QC measures.
Impact Joint poster presentations at ASMS and HUPO conferences. Sponsored seminars at various international conferences. VIP round table discussions on the advancement of precision medicine and the major challenges researchers face.
Start Year 2016
 
Description CRUK-Abcodia Science Advisory Board 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact I was invited to become a member of the Science Advisory Board for collaboration between Cancer Research UK and Abcodia, the biomarker validation company. The main reason for this collaboration is to develop new tests to detect various cancers before patients develop any symptoms.
Year(s) Of Engagement Activity 2013,2014,2015,2016,2017
 
Description Cub scouts visit to the Stoller 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 48 cub scouts aged 8-11 years old attended an evening visit to the Stoller Biomarker Discovery Centre where staff engaged in fun experiments designed to interest children in science. The feedback from the visitors has been very positive with additional visits from older scout troops planned for later in the year.
Year(s) Of Engagement Activity 2017
 
Description High profile visit from the Deputy Prime Minister and Manchester Alumni from Singapore 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact High profile visit from the Deputy Prime Minister and Manchester Alumni from Singapore on the 26th of March 2018.
Year(s) Of Engagement Activity 2018
 
Description MRC group on Stratification in next 30 years 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact MRC group on Stratification in next 30 years
Year(s) Of Engagement Activity 2019
 
Description NIHR BRC Workshop on Oncology Initiatives 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact NIHR BRC Workshop on Oncology Initiatives
Year(s) Of Engagement Activity 2019
 
Description School visit 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 14 children visited from a local primary school and participated in child-friendly protein science experiments related to our research, supervised by teachers and lab technicians.
Year(s) Of Engagement Activity 2017
 
Description Scouts visit 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Third sector organisations
Results and Impact 30 Scouts aged 10-11 attended an evening visit to the Stoller Biomarker Discovery Centre, including different protein science experiment stations related to our research.
Year(s) Of Engagement Activity 2017
 
Description Stoller Launch and Symposium 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A two day symposium with visiting speakers from across the UK and international precision medicine and proteomics communities. Attendees ranged from postdoctoral students, academics and industry representatives working in the field. There was also a formal launch event attended by our collaborative partners from SCIEX and the Danaher Corporation, and a ribbon cutting ceremony with representatives from the Stoller Charitable Trust who have provided funding to the Stoller Centre.
Year(s) Of Engagement Activity 2016
 
Description The Times, supplement called Future North 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact The Times (the supplement went into all copies of The Times in Yorkshire, North West and North East of England); a summary about importance of the Stoller Biomarker Discovery Centre in the biomarker discovery, validation and verification.
Year(s) Of Engagement Activity 2019
 
Description UK Biobank Enhancement Working Group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Development of a new multiomics approach on the UK Biobank cohort.
Year(s) Of Engagement Activity 2018,2019
 
Description UK Biobank's COO and Director of Operations visited Stoller Biomarker Discovery Centre 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact UK Biobank's COO Mark Effingham and Director of Operations Simon Sheard visited Stoller Biomarker Centre on the 21st of November 2018 to see the facility and to discuss future collaboration with Prof. Tony Whetton.
Year(s) Of Engagement Activity 2018