MRC Cambridge Lipidomics Biomarker Research Initiative (CLBRI)
Lead Research Organisation:
MRC Human Nutrition Research
Department Name: UNLISTED
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.
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.
Organisations
- MRC Human Nutrition Research (Lead Research Organisation)
- UNIVERSITY OF OXFORD (Collaboration)
- European University Viadrina Frankfurt (Oder) (Collaboration)
- EMBL European Bioinformatics Institute (EMBL - EBI) (Collaboration)
- University of Portsmouth (Collaboration)
- AgResearch (Collaboration)
- Thermo Fisher Scientific (United Kingdom) (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- National Research Council (Collaboration)
People |
ORCID iD |
Publications
Zehethofer N
(2008)
Plasma free fatty acid profiling in a fish oil human intervention study using ultra-performance liquid chromatography/electrospray ionization tandem mass spectrometry.
in Rapid communications in mass spectrometry : RCM
Koulman A
(2008)
Perspectives for Metabolomics in Human Nutrition: An Overview.
in Nutrition bulletin
Koulman A
(2009)
Semi-quantitative and structural metabolic phenotyping by direct infusion ion trap mass spectrometry and its application in genetical metabolomics.
in Rapid communications in mass spectrometry : RCM
Koulman A
(2009)
From differentiating metabolites to biomarkers.
in Analytical and bioanalytical chemistry
Koulman A
(2009)
Comparative High-Speed Profiling of Carboxylic Acid Metabolite Levels by Differential Isotope-Coded MALDI Mass Spectrometry
in Analytical Chemistry
Koulman A
(2009)
High-resolution extracted ion chromatography, a new tool for metabolomics and lipidomics using a second-generation orbitrap mass spectrometer.
in Rapid communications in mass spectrometry : RCM
Lee TV
(2010)
Structure of a eukaryotic nonribosomal peptide synthetase adenylation domain that activates a large hydroxamate amino acid in siderophore biosynthesis.
in The Journal of biological chemistry
Masoodi M
(2010)
Comprehensive lipidomics analysis of bioactive lipids in complex regulatory networks.
in Analytical chemistry
Pan X
(2012)
The lipid composition of isolated cytoplasmic lipid droplets from a human cancer cell line, BE(2)M17.
in Molecular bioSystems
Ubhi BK
(2012)
Targeted metabolomics identifies perturbations in amino acid metabolism that sub-classify patients with COPD.
in Molecular bioSystems
Lehrbach NJ
(2012)
Post-developmental microRNA expression is required for normal physiology, and regulates aging in parallel to insulin/IGF-1 signaling in C. elegans.
in RNA (New York, N.Y.)
Paschos GK
(2012)
Obesity in mice with adipocyte-specific deletion of clock component Arntl.
in Nature medicine
Johnson LJ
(2013)
An extracellular siderophore is required to maintain the mutualistic interaction of Epichloë festucae with Lolium perenne.
in PLoS pathogens
Osei M
(2015)
Hyphenating size-exclusion chromatography with electrospray mass spectrometry; using on-line liquid-liquid extraction to study the lipid composition of lipoprotein particles.
in Rapid communications in mass spectrometry : RCM
Johnson RD
(2015)
A novel family of cyclic oligopeptides derived from ribosomal peptide synthesis of an in planta-induced gene, gigA, in Epichloë endophytes of grasses.
in Fungal genetics and biology : FG & B
Prentice P
(2015)
Lipidomic analyses, breast- and formula-feeding, and growth in infants.
in The Journal of pediatrics
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
Jenkins B
(2015)
A review of odd-chain fatty acid metabolism and the role of pentadecanoic Acid (c15:0) and heptadecanoic Acid (c17:0) in health and disease.
in Molecules (Basel, Switzerland)
Eiden M
(2015)
Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes.
in Genome medicine
Forouhi NG
(2016)
Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.
in PLoS medicine
Hall Z
(2016)
Myc Expression Drives Aberrant Lipid Metabolism in Lung Cancer.
in Cancer research
Rocca-Serra P
(2016)
Data standards can boost metabolomics research, and if there is a will, there is a way.
in Metabolomics : Official journal of the Metabolomic Society
Jenkins BJ
(2017)
Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance.
in Scientific reports
Bond NJ
(2017)
massPix: an R package for annotation and interpretation of mass spectrometry imaging data for lipidomics.
in Metabolomics : Official journal of the Metabolomic Society
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
Stanley EG
(2017)
Lipidomics Profiling of Human Adipose Tissue Identifies a Pattern of Lipids Associated with Fish Oil Supplementation.
in Journal of proteome research
Sanders FWB
(2018)
Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption.
in Genome biology
Wittemans LBL
(2019)
Assessing the causal association of glycine with risk of cardio-metabolic diseases.
in Nature communications
Zheng JS
(2019)
Changes in plasma phospholipid fatty acid profiles over 13 years and correlates of change: European Prospective Investigation into Cancer and Nutrition-Norfolk Study.
in The American journal of clinical nutrition
Harshfield EL
(2019)
An Unbiased Lipid Phenotyping Approach To Study the Genetic Determinants of Lipids and Their Association with Coronary Heart Disease Risk Factors.
in Journal of proteome research
| Description | Ontario Genomics Institute's Scientific Advisory Group |
| Geographic Reach | North America |
| Policy Influence Type | Participation in a guidance/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 | European University Viadrina Frankfurt (Oder) |
| 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 | Academic/University |
| 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 | Academic/University |
| 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. none |
| 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. none |
| 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. No feedback yet |
| Year(s) Of Engagement Activity | 2012 |