INSERM is the French National Institute of Health and Medical Research. It is a public scientific and technological institute which operates under the joint authority of the French Ministry of Health and French Ministry of Research. INSERM has forged close partnerships with the other public and private research establishments as well as with hospitals to fulfill its missions. 80% of INSERM's 318 research units are currently hosted in university hospitals or cancer research centres.
Three INSERM units, located in Limoges, Toulouse, and Paris participate in the BioMargin project.

Description of the laboratories involved within the organisation. Background and facilities

UMR-S850 INSERM Limoges (Director: Pierre Marquet) is a research unit jointly appointed by INSERM, Limoges University and Limoges University Hospital. The unit is composed of 6 professors, 2 associate professors, 1 assistant professor, 5 physicians (in transplantation or pharmacology), 1-2 post-docs, 6-7 PhD students, 1 IT engineer, 2 lab engineers (technologists), 2 lab technicians, 1 clinical research assistant, 1 datamanager and 1 secretary. The unit research domain is "pharmacology of immunosuppressive drugs and transplantation", including research on urine biomarkers in renal transplantation since 2007. The unit has also set up a biobank of blood and urine samples from renal transplant patients, as part of an ongoing cohort study in three transplantation centres in France (PI: Pierre Marquet).
Pierre Marquet is also director of SCRABL, a "common facility for the analysis of biomolecules" cofinanced by INSERM, Limoges University and Limoges University Hospital, composed of three platforms (mass spectrometry, proteomics and NMR), each coordinated by an engineer. The mass spectrometry platform is equipped with nanoLC -- MALDI-TOF/TOF (AB Sciex 4800) and LC-LIT-MS/MS (AB Sciex 4000QTRAP).

Inserm U1048 Toulouse (PI: Dr Joost Schanstra) : The unit and the Children Hospital (part of the University Hospital) are located in Toulouse, France. The Children Hospital has a capacity of ~150 beds and the University Hospital of Toulouse was elected best hospital in a survey of the "Point" magazine in 2011.
The laboratory is internationally recognized for its expertise in the discovery of urinary biomarkers of renal disease in infants and identification of HNF1? mutations in renal developmental disease. In addition, using relevant animal models the laboratory has identified new antifibrotic molecules, including kinin and lysophosphatidic acid receptor antagonists. The laboratory runs two large national clinical projects on the discovery and validation of biomarkers in obstructive- and developmental nephropathies. This expertise is completed by strong "hands on" experience in molecular- and cellular-biology and renal pathology. Facilities: Access to paediatric patients. Multi biological level omics data gathering (miRNomics, transcriptomics, proteomics, peptidomics, metabolomics) and annotation. Host of the KUPKB (www.kupkb.org): a collection of omics data (multiple biological levels) of the kidney and urinary pathways. Multi biological pathway analysis (Ingenuity). Modern cellular and molecular biology wet lab for validation experiments in vitro and animal models of CKD.

Inserm Unit U845 Paris (PI: Dr Dany Anglicheau) is a Research Unit located on the Necker Hospital site, with the clinicians also working at the University Hospital Necker for their clinical work to ensure efficient translational research from bench to bedside. This activity provides the unique opportunity of developing clinical and translational researches, as well as basic science in transplantation immunobiology.

Contact persons active in BioMargin

INSERM-Limoges:
Prof Pierre Marquet, Dr Annick Rousseau,

Inserm –Toulouse :
Dr Joost P Schanstra, Dr. Jean-Loup Bascand, Dr. Stéphane Decraemer

Inserm-Paris :
Dr Dany Anglicheau

Inserm Transfert, private subsidiary of the French Institute for Health and Medical Research (Inserm) funded in 2001, will support the management of the BioMargin consortium.
The company has extensive expertise in two core areas:
i) Intellectual property management, technology transfer and exploitation of research results via its in-house lawyers, European patent attorneys and business developers;
ii) Management and coordination of FP7 and other international programs in biomedical research.
IT has a strong expertise in the FP7 financial and contractual rules. Having faced and solved many issues raised by the European cooperation in medical research, it can now anticipate and address quickly any kind of problems emerging in European collaborative programs. The company has already established management links with almost all life science organizations, including more than 50 biotech SMEs, in Europe.
Over the last 10 years, the European and International Department of Inserm Transfert has managed more than 25 FP6 & 32 FP7 projects in the field of life sciences and health. The Department of EU Affairs has a strong expertise in the financial and contractual rules of the FP7 program and all related regulatory aspects linked to European cooperation. It can anticipate and solve quickly any kind of emerging problems within large consortia. The Department of EU Affairs is certified ISO 9001.2008 since January 2010 for the management of European and International biomedical research projects.

Contact persons active in BioMargin
Dahlia Tsakiropoulos

The CNRS, (Centre National de Recherche Scientifique), is a public basic-research organization. It is the largest fundamental research organization in Europe. For BIOMARGIN, the ICSN (Institut de Chimie des Substances Naturelles) research unit will be involved.

The ICSN is one of its main units and the largest chemistry research institute in France or even in Europe, with approximately 270 scientists with more than 1250 publications in high cited peer reviewed journals and 41 patents in the last 10 years. The ICSN has an indisputable reputation is the field of natural compounds materialized and is known for the discovery of two major anticancer drugs (Taxotere® and Navelbine®) from natural sources.

The mass spectrometry team is equipped with modern and various analytical tools. This research group received an A grade during the 2009 evaluation campaign of the national evaluation agency AERES.

Contact persons active in BioMargin
Dr Alain Brunelle
Dr David Touboul
Dr Jean-Pierre Lecaer

The Necker Hospital is a university hospital, part of the Assistance Publique – Hôpitaux de Paris group, and is affiliated to the University of Paris Descartes. It offers a capacity of 400 beds for pediatrics and 200 beds for adults. Necker hospital is a place of history. The first transplantation was performed by Jean Hamburger at Christmas 1952 between a mother and her son, and a few years later, in 1959, a kidney transplant was successfully performed between 2 dizygotic twins several months after the same kind of transplantation had been performed in Boston. Since that time, more than 3,000 kidney transplants have been performed at Necker.
The Necker Hospital renal transplant program is one of the most active in Europe with ?200 adult and pediatric kidney transplantations per year. This activity provides the unique opportunity of developing clinical and translational researches, as well as basic science in transplantation immunobiology.

Contact persons active in BioMargin
Dr Dany Anglicheau
Pr. Rémi Salomon
Dr. Marina Charbit

The CEA, French Alternative Energies and Atomic Energy Commission, is a leading public body in research, development and innovation. CEA is a French government-funded technological research organization. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world. The agency is active in four main areas: health and information technologies, low-carbon energies, and defense/security. In each of these fields, the CEA maintains a cross-disciplinary culture of engineers and researchers, building on the synergies between fundamental and technological research. Within the CEA, the LIST institute (applied research on software-intensive technologies) is specialized in applied mathematics and computer science, interactive systems, signal processing and sensors with health being a strategic axis of application.

The DCSI, Department of Sensors, Signal and Information, belongs to the LIST Institute within the Technological Research Division of CEA. It shares its technological know-how and deep understanding of end-user for complex and multidimensional health data processing, analysis and modeling. Within the DCSI, the Laboratory of Data Analysis Tools develops innovative mathematical approaches and associated software platforms for signal processing, chemometrics, machine learning in the main "omic" fields (transcriptomics, proteomics, metabolomics) and in pharmacokinetics. The LIST has a strong experience in European projects (e.g. in health with FP5 "Computis" coordination on molecular imaging – also including Biomargin partners 5 and 11, and FP6 "ReaDNA" on next-generation sequencing) and industrial collaborations.

Contact persons active in BioMargin
Dr Nora Benhabiles
Dr Etienne Thevenot

The University of Leuven is the largest and oldest university in Belgium. The University Hospitals Leuven is the depending University Hospital, which has a capacity of 1900 beds, the largest in the country. The University Hospitals Leuven are very actively involved in clinical transplant care with internationally renowned programs of kidney, heart, lung, pancreas, liver, bowel, bone marrow and composite tissue grafts, and linked basic and translational research in transplantation.
Two departments are participating in the BioMargin project:
- Clinical Department of Nephrology and Renal Transplantation: Since 1963, kidney transplantation has been performed at the University Hospitals Leuven (Belgium), totalling more than 3500 patients. On average, 140 kidney transplantations are performed each year. The unit has been involved: in the major clinical trials with novel immunosuppressive drugs and regimens; and in large multicenter trials on steroid minimization, calcineurin inhibitor avoidance, CMV prophylaxis, etc. Protocol biopsies are routinely performed in all kidney transplant patients at our center, at implantation, 3 months, 1 year, 2 years and 5 years after transplantation.
- Laboratory of Nephrology: The team is involved in translational research in kidney transplantation, and has collected an extensive biobank of: DNA from both donor and recipients, biopsy mRNA and DNA (extracted at our site), serum and plasma samples.

Contact persons active in BioMargin
Dr Maarten Naesens
Prof Dirk Kuypers

VITO is a leading independent Flemish research and consulting agency active in the area of material and environmental science, energy, health, nutrition and chemical analysis. VITO counts approximately 600 highly qualified employees from diverse specialisations and collaborates with sector federations and their research centres, universities, colleges and European research institutes.

The Centre for Proteomics (CFP) is part of the Unit Environmental Risk and Health (MRG), that has a longstanding track record in FP7 projects. The labs of CFP, which is a collaboration with University of Antwerp, are equipped with both GC-MS/MS and LC-MS/MS equipment. The Centre is specialized in proteomics and peptidomics analysis, using state of the art equipment, such as the Thermo LTQ Velos orbitrap, the Waters Synapt G2 and the AB MALDI-TOF 4800. Not only the equipment, but also all the necessary expertise is present to cover all aspects of a proteomics workflow: sample prep, analytics and data analysis, integration and interpretation.

Mosaiques Diagnostics (MOS) is the leading specialist in clinical proteome and CE-MS analysis, currently the most advanced technology to identify disease-specific peptide and protein biomarkers in body fluids. MOS has published more than 100 manuscripts in leading journals and led the consortium that defined standards for clinical proteome analysis.
MOS main research activities are identification of biomarkers in body fluids for human diseases by capillary electrophoresis coupled to mass spectrometry (CE-MS); sequencing of peptide biomarkers, identification of posttranslational modifications, development of software solutions for multidimensional data analysis and establishment of proteome maps of human body fluids.
Contact persons active in BioMargin
Dr Jochen Metzger

The Hannover Medical School (Medizinische Hochschule Hannover, MHH), founded in 1965, is one of the world's leading university medical centres. Due to its interdisciplinary research, MHH has strong collaborative links with many academic and industrial research organizations worldwide. Building on a broad expertise in medicine, immunology, biochemistry, structural biology, genetics, cell biology and infectiology, MHH scientists study human diseases and develop innovative strategies for diagnosis, prevention and therapy. Main research activities focus on transplantation, stem cell research, infection biology, immunology and biomedical technology.
In the transplant centre for solid organs (lung, heart, liver, kidney, pancreas), 170 to 210 kidney transplantation are performed annually. Of these, approximately 35 are performed in pediatric patients.
Contact persons active in BioMargin
Dr Wilfried Gwinner

Cardinal Systems (French private SME) is a Clinical Research Organization, offering scientific and operational expertise, aiming to bring health innovation to patients. The company provides services to the pharmaceutical industry, biotechnology companies, governmental and non profit organizations. The company provides professional centralized services including: Randomisation; Logistics (therapeutic supplies, biological specimens); Medical Imaging; Clinical workflow systems; Management of independent committees. The company creates tailor-made clinical development projects for unmet medical needs and personalized medicine, through multidisciplinary project management methodology. In addition to centralized services, this includes individual monitoring, biometry, scientific writing activities.
With experience in early phase development studies through to Phase IV and epidemiology studies in various areas, Cardinal Systems is able to provide a full service with strong quality standards, scientific guidance and close follow-up throughout each of the development life cycles for therapeutics and biomarkers. Therapeutic Areas: HIV, Oncology, Auto-immune diseases, and Cardiovascular.

Contact persons active in BioMargin :

Antoine Perier, PhD
Rachel Madec, PhD

The C-TAC Laboratory (Analytical and Cellular Toxicology) belongs to the University Paris Descartes and is located at the University of Pharmacy. It is a research unit developing its own research programs and a series of collaborative projects with various partners.
The research team « Cellular and Analytical Toxicology » (EA4463) was created by the University Paris Descartes in January 2010 in order to explore new research fields in both experimental and analytical Toxicology. It brings together diverse skills including Toxicology, Analytical Chemistry and Biochemistry. Owing to its cell toxicology facility and its mass spectrometry platform, this team is able to propose multidisciplinary approaches to address complex toxicological issues. Several main axes have been defined including, in experimental toxicology, the mechanisms of oxidative stress and cell degeneration. The research topics in analytical toxicology are mainly focused on lipid markers of toxicity and concern different fields including neurodegenerative diseases and placental toxicology.
Contact persons active in BioMargin
Prof Olivier Laprévote
Dr Nicolas Auzeil

AcureOmics was founded in 2008 by Associate Professor Johan Trygg, Professor Torbjörn Lundstedt and Professor Thomas Moritz. The company is a leader in metabolomics and metabolic profiling of autoimmune diseases for instance Rheumatoid Arthritis (RA), diabetes, and Systemic lupus erythematosus (SLE). AcureOmics have also successfully studied drug treatment response and reactions to kidney transplantations. Together with clinicians, biotech companies, patient organizations and universities we develop therapeutic, diagnostic and prognostic biomarkers for more individual-based, personalized healthcare.
In addition to a modern NMR-facility at Umeå University, AcureOmics also have full access to the Swedish national metabolomics platform at the Swedish University of Agricultural Sciences (SLU) in Umeå. Since its launch in 2002, more than 45,000 samples ranging from plasma and cerebrospinal fluid to plants have been analyzed resulting in more than 40 research papers. The seven individual instruments available to AcureOmics cover both liquid and gas chromatography (LC and GC) coupled with mass spectrometry (MS).
Contact persons active in BioMargin
Prof Torbjörn Lundstedt
Dr Johan Trygg

The CHU Limoges is the owner of one of the 4 biobanks on which a large part of the project is built, and will be the sponsor of the BIOMARGIN European prospective cohort study.
The Department of Nephrology-Transplantation (Head: Prof. Marie Essig) and the Department of Pharmacology-Toxicology (Head: Prof. Pierre Marquet) at CHU Limoges will participate in the BioMargin project.
Contact persons active in BioMargin
Prof Marie Essig