Date : 10/06/2011

Internship proposal for : Master 1

Laboratory
AMIPEM (Alimentation, Microbiote Intestinal, Pathologies Encéphaliques et Métaboliques)
UMR 1319 Micalis - AgroParisTech INRA
Domaine de Vilvert Bat 440 RC-2
78350 Jouy en Josas
Website : http://www.jouy.inra.fr/
et http://www.micalis.fr/micalis/poles_et_equipes/pole_ecosystemes/amipem_gerard
Main discipline : Neurology
Lab director : Stéphane AYMERICH

Mentor
Patricia ANGLADE
email : This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
phone : 01 34 65 20 45

Subjects
1.: Gut microbiota / Brain axis - Brain development and functions - neuropsychiatric diseases
2.: Physiology - Fonctional genomic - Integrative biology- System biology
3.: Computational biology- Functional and structural annotation

Tools & Methodologies
1.: Brain dissection- proteomic analysis
2.: mass spectrometry - 2 D electrophoresis
3.: omics bioinformatic tools - data visualisation - data integration

Summary of lab's interests

The gastro-intestinal tract hosts a complex microbial community, the gut microbiota, whose collective genome coding capacity vastly exceeds that of the host genome. Gut microbiota is thus regarded as a full organ likely to affect the host physiology. For example, it plays a key role in the construction of the microvascular network of the intestinal mucosa, modulates the expression of host genes, locally in the gut mucosa, but also in other organs such as the liver. Recently, a metabolomics analysis of blood in germ-free and conventional mice showed that a large number of chemical species found in systemic circulation arise because of the presence of gut microbiota. The research interest of the team AMIPEM (Alimentation, Microbiote Intestinal et Pathologies Encéphaliques et Métaboliques) focuses on the role of gut microbiota (i) in the pathogenesis of liver inflammation consequent to obesity or alcohol consumption, and (ii) in the functioning of the gut-brain axis, with emphasis on the effect of gut microbiota on the neuro-endocrine and behavioural response to stress. To address these issues, AMIPEM scientists use germ-free rodents (mice and rats), whose gut can be colonised with human gut microbiota (gnotobiotic models).

Summary of project

The role of gut microbiota in the gut-brain axis has been lately highlighted. Patients with hepatic encephalopathy are improved after administration of oral antibiotics. Compared with conventional mice, germ-free mice exhibit an exaggerated hypothalamic-pituitary-adrenal (HPA) response to a restraint stress and we found recently the same results in germ-free rats submitted to an open-field test (manuscript in prep.). On the other hand, using different behavioural test systems, other authors showed lately that germ-free mice display an increased motor activity and decreased anxiety-like behaviour compared with conventional counterparts. Modification of the gut microbiota using administration of probiotics has been shown to modulate the HPA axis activity and brain monoamine concentrations. Indeed, in conventional rat pups, treatment with a preparation containing Lactobacillus rhamnosus and L. helveticus strains decreases the enhanced level of circulating corticosterone indu ced by maternal separation. In conventional adult rats, administration of a strain of Bifidobacterium infantis increases the plasma concentration of the serotonin-precursor tryptophan, while reducing the concentration of serotonin metabolites in the frontal cortex. Yet, mechanisms underlying behavioural and neuroendocrine alterations induced by gut microbiota remain to be elucidated. In this context, our aims are: - to establish in germ-free rats the profile of gene expression in brain regions involved in reactivity to stress and anxiety-like behaviour, using transcriptome and proteome analyses; - to study how transcriptome and proteome profiles are altered following colonisation of the gastro-intestinal tract by gut microbiota; - to relate these data with behavioural phenotype and neuroendocrine profile (blood corticosterone, brain monoamines) obtained in bacterial status-, gender- and age-matched animals. The Master student will participate to the proteomics part of the project, which will be performed in collaboration with Dr Franck Samson the operational manager of INRA platform Migale (http://migale.jouy.inra.fr/) of the Research Unit MIG (Mathématiques, Informatique, Génome). Access to the INRA platforms ICE (Iso Cell expression: http://www4.jouy.inra.fr/gabi_eng/Our-Resources/ICE-Integrated-Microgenomics-Platform) and PAPPSO (Plateforme d'analyse protéomique de Paris Sud-Ouest : http://pappso.inra.fr/), which are all located on the INRA campus of Jouy-en-Josas will be practised.