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laboratoire orphy
optimisation des régulations
physiologiques

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Call of interest for welcoming MSCA Post-Doc

Job title : Prevention of decompression sickness (DCS) : genetic and physiologic characterization of a new rat strain selectively bred for its resistance to DCS.

Key words : Physiology ; Genetic ; SCUBA diving ; Decompression sickness ; Precision medicine ;

Project context and objectives:

Decompression sickness (DCS) is is not only the most serious danger for self-Contained Underwater Breathing Apparatus (SCUBA) divers, but also an acknowledged risk of space flight and extravehicular activity, as well as air workers (hyperbaric chamber nurses, tunnellers). Symptoms of DCS range from skin rash, pain only and general malaise, to neurological symptoms of motor function impairment, loss of bladder/sphincter control, sensory impairment, permanent paralysis and even, ultimately, death (Vann, 2011).

Although the formation of venous gas emboli (VGE) during and after the decrease of environmental pressure is the primum movens of DCS, it was also estimated that the probability of DCS predicted from the highest VGE grades is only approximately 13%. DCS is associated with endothelial or vascular smooth muscle dysfunction, oxidative stress, platelet activation and inflammatory process. However, these factors have been studied independently and even if they are linked to DCS, none of these factors appear determinant in the onset of this pathology. Thus, the actual mechanisms leading to DCS are still puzzling, we still have no predictive marker of one’s individual susceptibility to DCS (for improved prevention) and the success-rate of treatment remains unchanged in 40 years, (at less than 80% complete recovery).

We recently developed a new murine strain by selecting Wistar rats based solely on their resistance to DCS. In a previous preliminary publication, we reported a 3 times decrease of DCS occurrence in these individuals after only 3 generations (Lautridou et al. 2017). To our knowledge, this strain represents the first evidence of inheritability of the susceptibility to DCS. It is also the only animal model with modified resistance to DCS. Therefore, we undertook to seek the molecular and physiologic mechanisms underlying the resistance to DCS.

Relevant approaches include investigations at both the molecular and physiological levels. Every three months a new generation of rats have been tested for resistance to DCS, and tissues were sampled and stored at -80°C. –omic approaches have been used to assess transcriptomic differences between resistant and susceptible rats, as well as the profiles of miRNA to understand the regulation of gene expression, and proteomic analysis for identification of biomarkers (for better selection of individuals) and better understanding of the mechanisms (for better treatment of the pathology).These molecular approaches have been coupled with a full array of functional physiological assessments.

The Marie‐Curie fellowship aims at characterize further the resistant strain and identify the mechanisms of the resistance to DCS. According to his/her field of expertise, the fellow will perform DNA analysis to determine whether DCS susceptibility is linked to different genes variants. Based on results from microarray and proteomic analysis, he/she will also assess the expression of candidate genes for resistance to DCS. Finally, data from these molecular approaches will be coupled with phenotypic traits obtained through physiologic approaches.

Litterature quoted:

Lautridou J, Buzzacott P, Belhomme M, et al (2017) Evidence of Heritable Determinants of Decompression Sickness in Rats: Medicine & Science in Sports & Exercise 49:2433–2438.
Vann RD, Butler FK, Mitchell SJ, Moon RE (2011) Decompression illness. The Lancet 377:153–164.

 

SUPERVISOR :

François Guerrero is full time professor at the University of Brest, Faculty of Sciences of Sport and Education. As a member of the research group ORPHY, he is the lead researcher on the physiopathology of SCUBA diving with special emphasis on the prevention of DCS. The approaches range from cellular and molecular to clinical experiments. Considering the field of SCUBA diving, Pr F. Guerrero has tutored 6 PhD students and published 28 articles in peer reviewed scientific journals during the last 5 years. He coordinated the PHYPODE European program, a 3.5 Million-euro research project funded by the Marie Curie Initial Training Networks (FP7-PEOPLE-2010-ITN, grant agreement n°264816).

Skills requirement :

The candidate must be experienced in experiments on animal models, and either molecular biology and/or physiology, with at least 1 publication per year since the PhD in 1st author.
She/he needs to speak English. French speaking is welcome but not mandatory.

CONTACT :

Pr François Guerrero
francois.guerrero@univ-brest.fr
332 98 01 67 42