MRC Cambridge Lipidomics Biomarker Research Initiative (CLBRI)

Lead Research Organisation: MRC Human Nutrition Research Group

Abstract

The proposal sets out the vision of creating an MRC led, internationally distinctive laboratory which has the capability to discover and use biomarker techniques to study the role of fats on health and disease (lipidomics biomarker research). Biomarkers are substances that are characteristic for specific biological processes; means to examine organ function or other aspects of health.

Modern practice in healthcare strongly moves from curing patient to disease prevention and early stage intervention, which helps to keep people out of the hospital and improve their quality of live and biomarkers play a crucial role herein. The development of many of today?s chronic diseases such as type 2 diabetes or heart disease is caused by changes in how fats are metabolised by the body. The ability to measure these changes will enable people to change their lifestyle or diet before it is too late. It also will help to monitor if change in lifestyle or diet result in the reduction of health risks.

People do not only develop heart disease by a bad diet, their genetics also plays a key role. Relating biomarkers to genes is essential to understand how diseases like diabetes and obesity arise on individual level. Biomarkers are also important to be able to measure how and which fats from the diet are metabolised. This will help to develop more suitable diets and understand how fats in diets can cause many of the now common diseases.

Although many laboratories in the world are working on the role of fat in diet an disease, the unique role of this laboratory lies in the fact that it does not only focus on discovery but also on application. This means that discovered biomarkers become available to healthcare community.

This centre of excellence will draw together worldwide expertise in the field, as well as utilising an already established scientific and clinical team based in Cambridge. The centre will not only pull together scientific and clinical expertise, but will also create a bioinformatics facility to collate and create a lipidomics database for use by others in the field. Providing a hub of new and emerging technologies within existing, well-established research groups, the centre will provide a unique teaching facility for scientists around the world to learn and develop the novel use of biomarker techniques.

Technical Summary

Advances in mass spectrometry have placed bioanalytical chemistry techniques at the forefront of the biological revolution, as key companion technologies to the cell and molecular biology tools that are rapidly advancing life science research. In the past decade, MRC HNR has developed into a national and international leader in human nutrition research in collaboration with a variety of external partners. MRC HNR now finds itself positioned to make a quantum advance over its current capabilities through the establishment of a ?MRC Cambridge Lipidomics Biomarker Research Initiative (CLBRI)? that would place MRC at the cutting edge of lipidomics biomarker research in the UK and worldwide. It would position MRC as a technology leader in using emerging technologies for nutrition and health research and add significantly to the Cambridge and UK capabilities in lipidomics research. It would also attract the world?s leading scientists to come and work with MRC researchers in Cambridge. The initiative described here is a collaborative effort of several MRC and academic partners and has the additional merit that it builds on MRC HNR?s core strengths. After three years, our aim is to have established 1) a fully functional, cutting-edge lipidomics biomarker research centre of excellence, 2) a state-of-the-art network of national and international partners and collaborators working in the CLRBI, and 3) a well-established and well-funded programme of frontier science ingrained in the new research lipidomics facility.

Publications

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Acharjee A (2017) The translation of lipid profiles to nutritional biomarkers in the study of infant metabolism. in Metabolomics : Official journal of the Metabolomic Society

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Bond NJ (2017) : an R package for annotation and interpretation of mass spectrometry imaging data for lipidomics. in Metabolomics : Official journal of the Metabolomic Society

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Faville MJ (2015) A QTL analysis of host plant effects on fungal endophyte biomass and alkaloid expression in perennial ryegrass. in Molecular breeding : new strategies in plant improvement

 
Description Ontario Genomics Institute's Scientific Advisory Group
Geographic Reach North America 
Policy Influence Type Participation in advisory committee
 
Description BBRSC DRINC
Amount £550,000 (GBP)
Funding ID BB/M027252/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2015 
End 09/2019
 
Description EU-FP6
Amount £426,000 (GBP)
Organisation Sixth Framework Programme (FP6) 
Sector Public
Country European Union (EU)
Start 04/2010 
End 04/2012
 
Description Brain isoprenoids in neurodegenerative diseases 
Organisation University of Frankfurt
Country Germany 
Sector Academic/University 
PI Contribution Development of the analytical techniques
Collaborator Contribution Development of the analytical procedures
Impact 19464372 18690423
Start Year 2007
 
Description Development of Lipid profiling techniques using FT-MS 
Organisation Thermo Fisher Scientific
Country United States 
Sector Private 
PI Contribution We provided samples for analysis and developed strategies for data analysis
Collaborator Contribution The collaborator provided access to analytical equipment and advice on analytical procedures
Impact 19347970
Start Year 2008
 
Description Fatty acid profiling 
Organisation National Research Council
Country Italy 
Sector Public 
PI Contribution Development of the assay
Collaborator Contribution Development of high resolution mass spectrometry aspects of the research
Impact 18523974
Start Year 2008
 
Description InterAct 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom 
Sector Multiple 
PI Contribution The Integrated Project InterAct is an EU funded large scale collaboration between nine European Countries and India, designed to: discover how genetic and lifestyle behavioral factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes
Collaborator Contribution we collaborate on the sample analysis
Impact multi-disciplinary: epidemiology, nutrition, analytical chemistry and bioinformatics. Funding from the EU obtained. SOPs established, material transfere agrement signed. base line paper published pub med ID: 21717116
Start Year 2010
 
Description Lipid mediator analysis lipotoxicity 
Organisation University of Cambridge
Department Institute of Metabolic Science (IMS)
Country United Kingdom 
Sector Academic/University 
PI Contribution A joint project to study the role of lipid mediators in lipotoxicity
Collaborator Contribution provided samples for analysis and joint design of experiments
Impact multi-disciplinary: lipidomics, cell biology, inflammation. Proof of concept experiments carried out and Joint funding proposal submitted.
Start Year 2010
 
Description PROMIS 
Organisation University of Cambridge
Department Department of Public Health and Primary Care
Country United Kingdom 
Sector Academic/University 
PI Contribution Lipid profiling of epidemiological samples using HR DIMS, to understand the genetic mechansims of lipid biosynthesis is relation to cardiovascular diseases
Collaborator Contribution Supplied samples and meta data
Impact Multi-disciplinary: Clinical epidemiology, bioinformatics, genetics, lipidomics, mass spectrometry Developed a joint approach to analyse this lipid profiling data in conjunction with epidemiological and genetical data.
Start Year 2009
 
Description The application of metabolomics in nutritional and genetical research 
Organisation AgResearch
Country New Zealand 
Sector Public 
PI Contribution Collaboration on meta-analysis of biomarkers, developing strategies for the analysis of metabolic profiling data in such a way that is can be combined with genetics data for QTL research
Collaborator Contribution Intellectual input, providing longterm overview of the field and providing genetical and metabolic profiling data for data analysis
Impact PubMed ID 19277615 PubMed ID 19551846 PubMed ID 19923209
Start Year 2007
 
Description Whole Body Fat Metabolism in Severe Insulin Resistance 
Organisation University of Cambridge
Department Institute of Metabolic Science (IMS)
Country United Kingdom 
Sector Academic/University 
PI Contribution When mechanisms for lipid storage are compromised, as in severe insulin resistance (SIR), dietary fat may exert an increased influence on the balance of macronutrients oxidised. This effect on the macronutrient oxidation system maybe comparable to that of carbohydrate in healthy individuals. We hypothesise that in SIR, positive fat balance may induce an increase in the rate of total and the proportion of recently ingested fat oxidised. We plan to study this using a combination of stable isotope tracer methods together with indirect calorimetry. Furthermore advances in magnetic resonance spectroscopy will allow us to explore the role of liver in buffering recently ingested fat in SIR, particularly SIR associated with lipodystophy.
Collaborator Contribution this partner pays for the MRS and calorimeter experimentsHelped in study design and recruitment of severe insulin resistant patients
Impact multi-disciplinary: Lipidomics, stable isotope analysis, medical imaging, endocrenology, nutrition. Ethics proposal is being completed.
Start Year 2010
 
Description Whole Body Fat Metabolism in Severe Insulin Resistance 
Organisation University of Oxford
Department Oxford Centre for Diabetes Endocrinology and Metabolism (OCDEM)
Country United Kingdom 
Sector Academic/University 
PI Contribution When mechanisms for lipid storage are compromised, as in severe insulin resistance (SIR), dietary fat may exert an increased influence on the balance of macronutrients oxidised. This effect on the macronutrient oxidation system maybe comparable to that of carbohydrate in healthy individuals. We hypothesise that in SIR, positive fat balance may induce an increase in the rate of total and the proportion of recently ingested fat oxidised. We plan to study this using a combination of stable isotope tracer methods together with indirect calorimetry. Furthermore advances in magnetic resonance spectroscopy will allow us to explore the role of liver in buffering recently ingested fat in SIR, particularly SIR associated with lipodystophy.
Collaborator Contribution this partner pays for the MRS and calorimeter experimentsHelped in study design and recruitment of severe insulin resistant patients
Impact multi-disciplinary: Lipidomics, stable isotope analysis, medical imaging, endocrenology, nutrition. Ethics proposal is being completed.
Start Year 2010
 
Description lipid mediators in inflammatory bowel disease 
Organisation University of Portsmouth
Country United Kingdom 
Sector Academic/University 
PI Contribution The relationship between mucosal polyunsaturated fatty acids (PUFA) bioavailability, inflammatory response and disease course in patients with inflammatory bowel diseaseLi
Collaborator Contribution Provided the samples and provided analytical standards, visiting scientist carries out work at HNR
Impact multi-disciplinary: lipidomics, inflammation, nutrition, experimental medicine. Material transfer agreement signed.
Start Year 2010
 
Description lipid metabolism prediction 
Organisation EMBL European Bioinformatics Institute (EMBL - EBI)
Country United Kingdom 
Sector Academic/University 
PI Contribution The aim of the collaborations is to use bioinformatics tools to predict the metabolism of lipids, this can be used to predict novel and unknown lipids.
Collaborator Contribution Developed bioinformatics tools
Impact Bioinformatics tools are jointly tested and improved, that are publicly available through the EBI.
Start Year 2010
 
Description Cambridge Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact describing how mass spectrometry and chromatography are used to separate lipids to children and adults.

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Year(s) Of Engagement Activity 2012
 
Description ChemNet Evening 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact An evening organised with RSC to show students, who are in years 12 and 13, the opportunities that are available to them after their A-levels in chemsitry.

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Year(s) Of Engagement Activity 2010
 
Description Gifted and Talented Masterclass 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact Year 10 masterclass at HNR entitled 'Searching for Health Clues' with hands-on activities for students to help them learn about the mass spectrometer.

None.
Year(s) Of Engagement Activity 2009
 
Description MP Pairing Scheme 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Scientist visit to spend a week with David Howarth MP.

None.
Year(s) Of Engagement Activity 2009
 
Description RSC afternoon 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Schools
Results and Impact An afternoon organised with RSC to show students, who are in years 12 and 13, the opportunities that are available to them after their A-levels in chemsitry. The students had a tour through the lab and could ask questions.

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Year(s) Of Engagement Activity 2012