Project coordinator organisation name: Utrecht University
TOWARDS A EUROPEAN LIPIDOMICS PROGRAM Publishable Final Activity Report
Contents page 1. Project execution 3 Project Objectives 4 Contractors Involved (for the duration of the project) 5 Work Performed and End Results 6 2. Dissemination and use 8 References 9
Annex 1 - Survey of expertise and infrastructure within the Lipidomics field Annex 2 - Plan for Using and Disseminating Knowledge
Annex 3 - Plan for Using and Disseminating Knowledge
(publishable version) Annex 4 - Final management report (pending) Annex 5 - Final report on the distribution of the Community's contribution (pending) Annex 6 - Questionnaires
TOWARDS A EUROPEAN LIPIDOMICS PROGRAM 1. Project execution The research areas that deal with the major chemical constituents that build up the cells in our body are referred to as genomics for genes and nucleic acids, proteomics for proteins and glycomics for carbohydrates. What has been missing in the “OMICS” realm is lipidOMICS. Since both carbohydrates and lipids are cellular metabolites, glycomics and lipidomics are subdivisions of metabolomics.
The time has come for generating broad insights into the role of lipids in physiology and pathology. Given that thousands of different lipids are present within a single cell and that many of these lipids are involved in modulating the processes of life in an area that is upcoming, lipidomics describes and quantitatively analyses the full complement of lipids, in for example body fluids, cells and tissues. Lipidomics integrates these data with knowledge of their protein targets, i.e. the metabolic enzymes and transporters, and of the relevant genes and the regulatory aspects of these physiological systems. Above all, an understanding of cell membranes will not be possible without understanding their lipid constituents.
Most important is the fact that many of the widespread diseases that plague humankind involve lipids. Prime examples are cardiovascular disease, obesity-related type-2 diabetes, and stroke. Other major diseases such as cancer and Alzheimer's disease also have a lipid involvement. In addition to these disorders of epidemic proportions, there are many other diseases that are directly caused by inherited defects in lipid metabolic enzymes and transporters, such as defects in cholesterol synthesis and lipid storage diseases. Lipids also play major roles in autoimmune diseases and act as (co-)receptors for bacteria, viruses and toxins. An increase in our knowledge of disease-related changes in lipid patterns and its integration into proteomic and genomic data will provide new basic biomedical insights; thus, far-reaching possibilities for diagnostic application (prognostic assessment, diagnosis and monitoring) as well as for the development of prevention and new therapeutic approaches can be expected.
Although lipid research was well developed in the initial era of biochemistry in the 1960s and 70s, it lagged behind the more recent developments of genomics and proteomics. One major problem has been the lack of technology to analyze the thousands of different lipids in body fluids and cellular systems. However, this problem is now quickly being overcome by exquisitely sensitive high-throughput mass spectrometric methods that are revolutionizing the field. Still, the application of such techniques to solving basic biomedical problems has remained rare and the clinical use of the potential of lipidomics is sparse. Finally, at the start of the present initiative there were no fora where basic biomedical scientists and clinicians would meet the technology developers, bioinformaticians and industrial stakeholders who can provide the infrastructure and the standardized kits needed for clinical testing.
Project Objectives The primary aim of the European Lipidomics Initiative (ELIfe) was to mobilize and organize key stakeholders, researchers and end-users in the area of metabolomics, especially lipidomics research, and to further define this field of research in terms of participants, scientific contents and strengths.
Objective 1: To network the field of metabolomics and to seek alliances with relevant stakeholders
The consortium should network and position the field of Lipidomics. Other areas of Metabolomics research like Glycomics and Signalomics (signaling lipids, lipid hormones) would be involved in all activities. Researchers, stakeholders from the health care profession and from industry with special emphasis on SMEs would be invited to join ELIfe activities at the earliest possible stage.
Objective 2: To link the field of metabolomics to the genomics and proteomics initiatives
One special challenge was to adapt bio-informatics as devised for Genomics and Proteomics to the field of Metabolomics. The choice of the technology to be used would define the type of bio-informatics approaches necessary to deal with the large body of data expected from Lipidomics and in a wider sense Metabolomics.
Objective 3: To define a strategy for metabolomics research, using lipidomics as example
Lipidomics was subdivided into three areas of development: i) technology, ii) cell biology, and iii) health. Experts in these areas were to be joined in a series of workshops to define where these areas would gain most from a European collaboration and what direction of research would most likely bring breakthroughs. The topic of lipid rafts would be taken as a theoretical test case to define the kinds of experimental data that can be generated by high-throughput approaches in this field, and to determine how these data sets could be most useful for medical application.
Objective 4: To initiate an Expertise Platform on Lipidomics
As a first step to fully mobilize the field, an awareness of the strength and expertise was to be created. Via a survey of expertise, to be published on the web and via a specific workshop on Lipidomics and Technology, a virtual Expertise Platform would be initiated and linked to the Euro Fed Lipids organization. It was to become a test centre for bench marking of new Lipidomics technology.
Objective 5: To hold both science-related as well as policy meetings
A series of scientific and strategic meetings had to be organised. (a) Workshops with a focus on technology and terminology, on basic science and on medical applications of metabolomics and of lipidomics in particular. (b) Networking meetings and applications meetings should join academic scientists across the life sciences, clinical laboratory scientists, clinicians and industrial representatives. (c) The concluding conference should be open to policy makers as well as the above mentioned representatives, and specific round tables were to be organized for this purpose.
Contractors Involved (for the duration of the project)
Lipidomics Expretise Platform: www.lipidomics-expertise.de Work Performed and End Results Expertise Platform and the inventory of stakeholders (Objectives 1 and 4).
The Lipidomics Expertise Platform was launched on the internet in November 2005. The database was used to prepare a survey of the lipidomics expertise and infrastructure in Europe. A database containing 2,500 active e-mail addresses was used to mobilize lipidologists for the concluding ELIfe meeting. Scientists from industry were specifically invited for the first workshop (Dresden, 2005) focusing on lipidomics technology, which led to the exchange of ideas on technological possibilities versus the needs of the scientists in the field.
Contacts were established between ELIfe and related initiatives in the US (LipidMAPS) and Japan (LipidBank). As a first collaborative step, a common lipid classification scheme has been devised and published [1-3]. In this context, professors Spener and van Meer were invited to become members of the International Lipid Classification and Nomenclature Committee (ILCNC), which has taken on the task of updating and expanding the classification system. The committee concluded its first meeting on July 7, 2006, with a list of recommendations in the light of a continuously evolving inventory of biological lipid structures.
Lipidomics versus genomics/proteomics and the need for bioinformatics (Objective 2).
Genomics, proteomics and metabolomics experts were invited to present their points of view at the ELIfe kick-off meeting. The recognized need for specific bioinformatics approaches was then addressed by inviting the lipid MAPS experts for the first technology workshop in Dresden, and subsequently by active participation of ELIfe members (with LipidMAPS representatives) in an extra workshop at the European Bioinformatics Institute in Hinxton that concentrated on connectivity between different types of databases, the willingness of EBI to provide the physical storage space for lipid databases, and the curation of existing databases. This resulted in the involvement of EBI experts in the later ELIfe-based FP7 lipidomics application LipidomicNet.
Devising a strategy for lipidomics research (Objective 3)
Experts in three areas of development of lipidomics: i) technology, ii) cell biology, and iii) health, were collected in three workshops to discuss progress in their subfield and to define what would be the best way to stimulate lipidomics research in Europe. Experts in technology were brought into contact with basic scientists and clinicians at an industry workshop, that was positioned as a satellite meeting to the concluding ELIfe/FEBS special meeting in Noordwijkerhout (NL). The outcome of this meeting, which attracted over 60 scientists, was a round table discussion on technologies available, on instrument development, and on application of these in society, where possible in high throughput mode. A second workshop in Bilbao (E), cosponsored by EMBO, brought together basic scientists in physics, chemistry and biology who focused on the theme of lipid rafts, membrane substructures of exciting functions, and the possibilities to further characterize these structures using novel technologies. In a final workshop on 'Lipidomics and Health' preceding the 2006 ICBL meeting in Pécs (HU), life scientists and clinical scientists discussed the applications of novel and high-throughput lipidomics technology in medical applications.
In line with the workshops, the following papers were published, each of which included a conclusion/perspective section: 'Cellular Lipidomics', 'Lipidomic strategies to study structural and functional defects of ABC-transporters in cellular lipid trafficking' and 'The European Lipidomics Initiative: Enabling Technologies' [4-6]. In addition, a white paper under the title 'Enabling Technologies for Studying the Genome, Proteome and Cytome of the Lipidome' was published as an interactive paper on the ELIfe website . A series of editorials by ELIfe members served to critically evaluate future developments in lipidomics [8-13]. In addition, ELIfe members formed an interest group with other lipid scientists to prepare a policy document for the European Science Foundation under the title: 'Structural Medicine II: the Importance of Lipidomics for Health and Disease' .
To pursue possibilities to apply for lipidomics funding under FP7 two meetings were organized in 2006 and 2007 for ELIfe members plus other interested scientists in Frankfurt (D). This eventually resulted in the successful FP7 application LipidomicNet. A EuroCORE theme proposal EuroMEMBRANE by a team led by the ELIfe chair has been accepted by ESF, with an expected call for research grant applications in early 2008 .
Science-related and policy meetings (Objective 5)
A series of scientific and strategic meetings has been organised. Besides the technology workshop in Dresden (2005), and the three workshops in Bilbao, Pécs an Noordwijkerhout, ELIfe contributed sessions to four industrial and life science meetings: (1) the 2005 conference of the European Life Sciences Organization (ELSO 2005) in Dresden (D), was attended by 1,200 scientists, amongst whom 40% PhD students. The program consisted of 6 plenary sessions, 21 minisymposia, 3 poster sessions and 7 sub-group meetings. ELIfe contributed Minisymposium 1: Lipidomics. (2) the 26th World Congress and Exhibition of the International Society for Fat Research (26th ISF World Congress) in Prague (CZ) 2005, hosted by the Czech Chemical Society and Euro Fed Lipid: 'Modern aspects of fats and oils - A fascinating source of knowledge'. The session on 'Lipid Bioscience and Genomics' to this industrial meeting was sponsored by ELIfe. (3) the 47th International Conference on the Bioscience of Lipids (ICBL - ELIfe – ILPS joint meeting), 2006, in Pécs (HU): two sessions on 'Lipidomics' and 'membrane microdomains' to an audience of basic lipid scientists. (4) the 4th Euro Fed Lipid Congress, 'Fats, Oils and Lipids for a Healthier Future - The Need for Interdisciplinary Approaches', Madrid (E), 2006. One session was contributed on 'Lipid Mediators and Lipidomics'. This was a meeting with an industrial character.
The concluding general ELIfe meeting 'New concepts in lipidology: from lipidomics to disease' in Noordwijkerhout, NL, 2006, was cosponsored as a FEBS special meeting and was attended by over 250 participants The meeting hosted a short joint symposium between the Nordrhein-Westfälische Akademie der Wissenschaften and the Dutch Royal Academy of Arts and Sciences. A special ELIfe issue of FEBS Letters under the title 'Lipidome and Disease' was distributed at the meeting .
2. Dissemination and use Over 2005 and 2006, the specific support action 'the European Lipidomics Initiative (ELIfe)' has resulted in four successful workshops where stakeholders from basic science, industry and medicine met to discuss cell biological, technological, industrial and clinical aspects of lipidomics. In addition, ELIfe contributed lipidomics sessions to four networking meetings, one on life sciences, one on the bioscience of lipids and two industrial lipid meetings. These workshops and meetings culminated in the concluding general meeting in October 2006, attended by a broad audience of 250 scientists. At the occasion of this meeting a special journal issue was published on 'Lipidome and Disease' . The results of the the specific support action were reported in a series of policy papers in the scientific literature [4-6, 8-13], and a policy briefing on lipidomics and health of the European Science Foundation . In addition, ELIfe contributed to a number of technical papers on lipid classification and data handling [1-3] and to a 500 page document entitled 'Enabling technologies for studying the genome, proteome and cytome of the lipidome.' . This document will be presented on the Lipidomics Expertise Wiki Portal (LEP-Wiki): http://www-cgi.uni-regensburg.de/Klinik/Klinische_Chemie/lipidWiki/, to allow a direct interaction with the scientists in the field. Interviews with ELIfe members appeared in various journals [17,18].
A survey was prepared based on registrations in the Lipidomics Expertise Platform www.lipidomics-expertise.de with the purpose of identifying stakeholders and providing insight in the available expertise, which can be used for contacting specific centers for collaboration. A 260 page document entitled 'Lipid droplets and lamellar bodies as dynamic organelles connecting influx, efflux, and storage of lipids: Translational research towards human disease' was prepared as the basis for a grant proposal under FP7 by a number of ELIfe members plus other scientists. This proposal 'LipidomicNet' was recently selected for funding. A EuroCore theme proposal under the name EuroMembrane  has been accepted by the European Science Foundation and a call for applications is expected for early 2008.
In summary, we believe that the European Lipidomics Initiative has created many opportunities for crossover between basic science and medical and commercial applications, and that it has inspired stakeholders to seek contact and establish strategic alliances. Because national funding agencies and policy makers value the European dimension, the project will impact on both the European and the national level in shaping policies and research activities, both in applied and fundamental research. One such field is that of nutrition and health. Technology development will allow more detailed analyses of lipid patterns in diseased and healthy persons, which will drive discussions with the food industry concerning the potential positive and negative effects of different types of (lipid) nutrition on human health with new health policies drawn up as a result.
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 van Meer, G. (main proposer), Malhotra, V., Marsh, M., Simons, K., van der Goot, G., Warren, G. (2008) Membrane Architecture and Dynamics (EuroMEMBRANE), EuroCORE theme proposal. Call to be launched in spring 2008.
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European Lipidomics Initiative: Shaping the Life Sciences