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A word from the director

Circulation – Haemostasis - Cardiology – Pneumology - Nutrition - Diabetes - Obesity - Endocrinology - Gastroenterology - Hepatology - Nephrology – Dermatology - Osteoarticular system

Ferritin crystal. Ferritin an iron-storage protein in the liver, spleen and bone marrow - Copyright Inserm, J. Breton-Gorius

Ferritin crystal. Ferritin an iron-storage protein in the liver, spleen and bone marrow.

The Physiopathology, Metabolism and Nutrition Institute covers a very broad field of physiology, experimental medicine and human diseases. The areas covered are the lungs, heart and blood vessels, haemostasis, endocrine glands, liver, kidneys, skin, bones and joints, and all the organs involved in nutrition, from controlling appetite and dietary behaviour to the digestive processes and control of the use and storage of substrates.

The Institute is based on an Expert Committee representing each of the subject areas and representing the various research organisations involved. Research efforts are split, 29% in cardiovascular and haemostasis, 25% in metabolism, nutrition and diabetes, and 46% spread almost equally across osteoarticular, pneumology, nephrology, hepatology, endocrinology, gastroenterology and dermatology.

Medico-scientific challenges

Metabolic and nutritional diseases are a major public health issue, because of their complications, particularly cardiovascular. Diabetes, hyperlipidaemia, obesity and kidney failure are major precursors of cardiovascular diseases, leading cause of death in industrialised countries. The continuing high incidence, despite major therapeutic advances, is explained by the increasing incidence of diabetes, obesity and ageing of the population. Diabetes alone affects 7.1% of the French population aged between 20 and 70 years old, obesity about 15%. Paradoxically, malnutrition is also a major problem. Malnutrition is observed in 40% of chronic diseases, in 30% to 50% of hospital patients, taking all pathologies combined. Other diseases falling into the Institutes subject areas are frequent and/or serious. They pose fundamental questions, whether they are autoimmune and inflammatory diseases, perfect example of multigenic and multifactorial diseases, monogenic genetic diseases, often disabling, numerous cancers or infectious diseases.

The biological problems posed involve a huge spectrum of disciplines, from genetics to developmental biology, cell biology, immunology, imaging, engineering, the biology of ageing and clinical research. The spectacular increase in the incidence of common diseases poses the question of the role of the environment as well as its interaction with a genome whose variability is becoming accessible as these diseases appear suddenly. Apart from rare monogenic diseases, common diseases are arising across a multigenic field that combines gene variants controlling as many intermediate phenotypic traits. Besides the genes that contribute to initiating these diseases, others yet to be identified contribute to their progression. These diseases require us to have biomarkers for their triggering and progression. There is a priority need for relevant preclinical models and extensively phenotyped patient cohorts.

For many of these diseases, current treatments are inadequate, often symptomatic or palliative. When they are based on mechanisms, they often clash with the risks they cause. When a preventive measure exists (atherosclerosis), it is often limited to targeting associated risk factors, which could only typify the physiopathological mechanisms involved. Organ replacement strategies, widespread in numerous fields of medicine, come up against the shortage of donors, the toxicity of immunosuppressants or the complexity of the surgical procedure. Changes are unavoidable to generate cells or tissues in vitro for use in transplants, to develop cell regeneration strategies, to make the immune system tolerate transplanted organs or to create artificial organs.

The Institute's priorities

They are of three types: scientific, organisational and technological.

Alignment of osteoblasts responsible for bone formation - copyright Inserm, G. Boivin

Alignment of osteoblasts responsible for bone formation

Ten scientific priorities have been identified:

  • Gene-function-environment interactions based on essentially epigenetic processes orchestrated by the diversity of the genome.
  • Mechanisms of common diseases, which falls within a continuum initiated from the first development phases, ranging from physiology to pathology, justifying new hypotheses at the origin of their triggering and/or progression.
  • Consequences of inflammation, cellular senescence and ageing in physiology and pathology.
  • Integrative physiopathology taking account of multiples and complex interactions between organs and between central and peripheral nervous systems.
  • Preclinical models (humanised mice, cell models, stem cells (iPS)).
  • Preclinical and clinical phenotyping integrating data from high speed biology and new biomarkers to nosological division of common diseases.
  • Optimising the use of biological resource banks (blood, plasma, DNA, tissues) and resource centres focusing the use of data banks.
  • Innovative therapies based on physiopathology and organ replacement strategies.
  • Opening up fundamental research and cross-disciplinary and clinical research, and interdisciplinary research, integrating physics (biomaterials), chemistry, mathematics (interpretation and robustness of high speed biology data, modelling).
  •  Balance between emergence and targeted research, by relying on strong fundamental research (epigenetics arose from plant biology).

The 9 functional priorities are:

  • Groups, themed and unthemed, combining research and hospitals, on sites creating efficient technical platforms to ensure a critical mass, visibility and broad opportunities for interactions, by relying on structures arising from future investments or local vocation (DHU).
  • Filling the persistent gulf between the identification of biological targets that remains beneficial and the transfer to clinical application, often failing, and creating academic platform dedicated to clinical conversion of academic discoveries.
  • Interactions in precompetitive projects between academic laboratories, biotechnology and industrial companies on the basis of a complementarity necessary to develop innovative diagnostic or therapeutic approaches.
  • Emergence and recruitment of young teams within sites identified by the scientific level and critical mass that they represent.
  • Maintain a significant pool of technicians and engineers within platforms, but also teams of which they are an active memory.
  • Adapt the length and conditions of employment contracts to the special requirements of research carried out as part of project finance. 
  • Major, coordinated effort to develop European projects and encourage team to respond to calls for tenders. 
  • Balance between recurring grants and project finance.
  • Integration of research strategies of multiple French organisations working in life sciences.

Finally, the technological priorities relate to continuing to implement metabolomic platforms coordinated with existing genomic, transcriptomic and metabolomic platforms and to develop bio-informatics and biostatistics platforms. This technological policy must be considered in a coordinated way with objectives set by other institutes, particularly in the field of genetics and the genome, inflammation, public health and, of course, healthcare technologies.

Christian Boitard
Director of the Physiopathology, Metabolism and Nutrition Institute

 

 

 

 

 

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