Development of validated assays for the evaluation oxidative stress in health and disease.

Lead Research Organisation: University of Leicester
Department Name: Cancer Studies and Molecular Medicine

Abstract

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Technical Summary

Overarching objective: a successful partnership between Leicester and Biotage.

1. Timing. Leicester?s biomarker research fits perfectly with Biotage?s planned move into

the biological sciences market. The collaboration with Leicester will provide reputation and

assays, generating a strong and credible market presence.

2. Expertise. Leicester has an international reputation in the field of biomarkers, mass

spectrometry, and biomarkers of oxidative stress. However, to expand the repertoire of DNA

lesions studied, and to develop high throughput analysis, requires knowledge of SPE

chemistry, and associated equipment. Biotage has extensive expertise and is the market

leader in the development of SPE chemistry and technology.

3. Exchange. Items (1) and (2) provide significant scope for technology and knowledge

exchange.

4. Economic benefits. Oxidative stress receives widespread interest, yet there is a

paucity of robust commercial assays. This collaboration represents an important route, by

generating competitive advantage, to establish a significant stake in a growing market .

Research excellence. The proposal builds upon research excellence in oxidative stress and

biomarkers represented by MSC/Leicester. MSC leads of one of the foremost oxidative stress

groups in the UK, illustrated by numerous awards, and a total of 76 publications; 55 in peerreviewed

journals (48% in the top oxidative stress journals) and 21 book

chapters/reviews/commentaries including co-editing one book. MSC is chair of the EU FP6

funded international ESCULA (www.escula.org) project comprising > 30 labs/SMEs, validating

urinary DNA biomarkers for large-scale human studies.

Importance. DNA oxidation, derived from both endogenous and exogenous sources, is

considered important in the pathogenesis of numerous diseases with significant worldwide

impact e.g. cancer, cardiovascular and neurodegenerative disease, hence strong interest from

academia and industry. Widely used as biomarkers of generalised oxidative stress, these

markers may also inform on DNA repair, crucial to genome protection. However, there is a

paucity of robust biomarker assays validated to GCLP, which largely confines the potential

market to non-clinical, academic research. The proposed partnership is uniquely placed to

address this gap in a significant market, to provide robust oxidative stress assays that could

be used to address numerous MRC strategic research areas. For example: Stratification of

phenotype (e.g. asthma); Tracking response to intervention (e.g. chemoprevention);

Measure, understand and modify environmental and inherited influences on health (e.g.

exposure to UVR or airborne pollutants); Exploitation of world leading position in hypothesisgenerating

science to deliver improved health (e.g. high-throughput assays of oxidative stress

for molecular epidemiology); Development of new interventions (DNA repair targets in

cancer).

Justification for the collaborating partner chosen. Biotage are seeking to make a large-scale

move into the biological science applications market. This will add to their existing portfolio

(Forensic, Environmental and Agrochemical and Food). To make this move credible, and

demonstrate application for their products to the biological/health sciences Biotage requires a

pairing with a prominent academic group. We request support to determine the potential size

of the collaboration between Leicester and Biotage. This will include generation of pilot data

from novel assays to support Leicester?s biomarker interests and Biotage?s proposed move

into the biological science applications market.
 
Description University of Leicester Innovation Fellowship
Amount £9,964 (GBP)
Organisation University of Leicester 
Sector Academic/University
Country United Kingdom
Start 04/2012 
End 03/2013
 
Title UHPLC-MS/MS of 8-oxodG 
Description Rapid UHPLC-MS/MS method for 8-oxodG in a variety of human biological matrices e.g. urine, serum, plasma, seminal plasma, amniotic fluid, peritoneal fluid. 
Type Of Material Technology assay or reagent 
Year Produced 2012 
Provided To Others? Yes  
Impact Urine volume and assay time have both been significantly decreased compared to exisitng methods. 8-oxodG had not been previously detected in some of the above matrices. 
 
Description Biotage 
Organisation Biotage
Country Sweden 
Sector Private 
PI Contribution Expertise in understanding the sources and analysis of DNA damage products in extracellular matrices. This resulted in a novel UHPLC-MS/MS method for 8-oxo-7,8-dihydro-2'-deoxyguanosine in a variety of human, biological matrices (PMC3404459). This then generated a product application note for Biotage.
Collaborator Contribution Biotage made significant in-kind contributions and access to their facilities, equipment and technical expertise.
Impact Lam, PMW., Mistry, V., Marczylo, TH., Konje, JC., Evans, MD. and Cooke, MS. (2012) Rapid measurement of 8-oxo-7,8-dihydro-2'-deoxyguanosine in human biological matrices using ultra high performance liquid chromatography tandem mass spectrometry. Free Radic. Biol. Med. 52, 2057-2063. Extraction of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) from biological fluids using ISOLUTE ENV+. Biotage product application note.
Start Year 2011
 
Description ESCULA 
Organisation Chung Shan Medical University
Country Taiwan, Province of China 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation Columbia University
Department Department of Environmental Health Sciences
Country United States 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation Copenhagen University Hospital
Department Laboratory of Clinical Pharmacology
Country Denmark 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation Ege University
Department Department of Pharmaceutical Toxicology
Country Turkey 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation European Space Agency
Department ESA Laboratories
Country European Union (EU) 
Sector Public 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation Flemish Institute for Technological Research (VITO)
Department Environmental Risk and Health Unit
Country Belgium 
Sector Charity/Non Profit 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation Heidelberg University
Department Institute for Occupational and Social Medicine
Country Germany 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation Institute of Experimental Medicine AS CR
Department Laboratory of Genetic Ecotoxicology
Country Czech Republic 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation Japan Institute for the Control of Aging (JaICA)
Country Japan 
Sector Private 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation Lund University
Department Sections for Metals and Health
Country Sweden 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation National University of Defense Technology
Country China 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation Nicolaus Copernicus University in Torun
Department Department of Clinical Biochemistry
Country Poland 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation Philippe Auguste Laboratory
Country France 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation Stockholm University
Department Department of Genetics, Microbiology and Toxicology
Country Sweden 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation University of Copenhagen
Department Department of Public Health
Country Denmark 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation University of Occupational and Environmental Health
Department Department of Environmental Health Engineering
Country Japan 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation University of Parma
Department Department of Clinical & Experimental Medicine
Country Italy 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation University of Parma
Department National Institute for Insurance against Accidents at Work
Country Italy 
Sector Public 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description ESCULA 
Organisation University of Valencia
Department Biochemistry and Molecular Biology Department
Country Spain 
Sector Academic/University 
PI Contribution Chaired the European Standards Committee of Urinary (DNA) Lesion Analysis (ESCULA). Led and contributed to grant applications and publications plus coordinated inter-laboratory validation studies.
Collaborator Contribution Contributed to grant applications, publications and inter-laboratory validation studies.
Impact Grants and publications
Start Year 2007
 
Description NIBOIRE 
Organisation Forsite Diagnostics
Country United Kingdom 
Sector Private 
PI Contribution Leadership of the consortium, biomarkers of oxidative stress expertise
Collaborator Contribution Expertise in specific technologies, health risk assessment and radiobiology.
Impact Confidential
Start Year 2012
 
Description NIBOIRE 
Organisation Japan Institute for the Control of Aging (JaICA)
Country Japan 
Sector Private 
PI Contribution Leadership of the consortium, biomarkers of oxidative stress expertise
Collaborator Contribution Expertise in specific technologies, health risk assessment and radiobiology.
Impact Confidential
Start Year 2012
 
Description NIBOIRE 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution Leadership of the consortium, biomarkers of oxidative stress expertise
Collaborator Contribution Expertise in specific technologies, health risk assessment and radiobiology.
Impact Confidential
Start Year 2012
 
Description NIBOIRE 
Organisation l'Institut de Recherche Biomédicale des Armées
Country France 
Sector Public 
PI Contribution Leadership of the consortium, biomarkers of oxidative stress expertise
Collaborator Contribution Expertise in specific technologies, health risk assessment and radiobiology.
Impact Confidential
Start Year 2012
 
Title ISOLUTE ENV+ 
Description Use of ISOLUTE ENV+ for the extraction of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) from biological fluids. MRC most recent principle source of funding for this development. 
Type Support Tool - For Medical Intervention
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2012
Development Status Under active development/distribution
Impact Increased the speed and ease of sample throughput