Physiopathology, Metabolism, Nutrition

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Scientific challenges

Diseases of the heart and blood vessels, lungs, endocrine tissues, liver, kidneys, digestive tract, skin, bones, joints are specific to the organs affected. But they can be understood and treated without taking account the numerous interactions between the body and its environment.

Cross-disciplinary aspects of physiology and pathology are therefore a major issue for the Institute. This is all the more true given the various diseases involved arising from essentially common mechanisms. They are often diseases arising against a background of genetic predisposition, but interacting closely with the environment and its sometimes sudden upsets. We often know little about the triggering mechanisms due to:

• still insufficient knowledge of the genetic polymorphism involved in their aetiology, genes and proteins functionally expressed in the tissues involved and their interaction with the environment;
• incomplete modelling of physiopathological mechanisms leading to the initiation and then the advance of the disease in the tissues.

The consequence of it is often inadequacy of available treatments, rarely appropriate to the origin of these common diseases. Knowledge of the mechanisms of diseases is also likely to lead to defining new biomarkers, which we can hope will improve the diagnosis, prognosis and choice of treatment for these diseases.

Several opportunities for progress are therefore identified. Genomics and proteomics are a major issue for better understanding of normal function of the tissues and their interactions with the environment. This means developing functional genomics, characterising the tissues in which the newly discovered genes are expressed, but also using comparative genomics and proteomics to understand the development of tissues (from gene to organ), ageing mechanisms, and signalling routes that enable the tissues to function. Epigenetics and metagenomics are new fields, and it is thought they will be drivers in the study of gene-environment interactions. The diseases covered by the Institute are generally multifactorial, so their models should include their three triggering levels and their progression: genetic predisposition (these are multi-genetic diseases involving genes that are normal but not exactly the same in different individuals), cellular circuit implicated by each gene identified, and environmental factors. Work on targeted cohorts allow the clinical phenotypes of different diseases to be analysed and the causes of their frequent variability to be researched.

A major issue in these diseases is to implement appropriate treatment. Currently available treatments often remain unsatisfactory, for various reasons. Some are only palliative or symptomatic (hormonal substitutes for endocrine diseases, dialysis in the final phase of kidney diseases, organ transplants, etc.). Others are non-specific and led to side effects (immunosuppressive treatments in inflammatory or auto-immune diseases). We are also missing treatments to eliminate the after-effects of ischemia on the organs affected. And yet opportunities are identified to improve and individualise treatments: molecules specifically targeting inflammatory pathways, purification and injection of monoclonal antibodies, cellular biotherapies intended to produce tissues and organs from the patient's stem cells... But today these biotherapies remain the field of research, already rarely of clinical investigation. Advances in the knowledge of risk factors also allow the development of individualised predictive medicine and better targeting of preventive messages addressed to the population.