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PhD opportunities
PhD opportunities

Subject 1: Mechanisms of the epigenetic memory during the development

Team:
Epigenetics: Proliferation and differentiation

Supervisors:
Thesis Director: Christophe THIRIET (Christophe.Thiriet@univ-nantes.fr / 33 (0)2 51 12 57 64)
Thesis co-supervisor: Gwenola AUDA-BOUCHER (gwenola.boucher@univ-nantes.fr / 33 (0)2 51 12 56 33)

Thesis project:
Numerous pathologies involve dysfunctions within the gene regulations. It is well-established that chromatin is a critical player that affects the genetic activities, which brought to a novel research domain, the epigenetics. A characteristic of this epigenetic regulation is the inheritability leading to the transmission of the information from the mother cell to the daughter cells. Nonetheless, the mechanisms of the epigenetic memory remain unclear. The work aims by an original approach exploiting the chicken-mouse chimera in conjunction with genomic analyses to identify the alterations of the epigenome during the development of the limb bud and to understand its functioning using experimental perturbations. Initially, the comparison of the changes of the chromatin marks occurring during the development in utero and ex vivo will be performed. These analyses will lead to the identification of unchanged chromatin marks and those that are altered by the different bud limb development approaches. In contrast to the in utero development, the chicken-mouse chimera offers the continuous access to the biological material. This advantage will be used to generate epigenome perturbations and to evaluate their effects within the cell differentiation and the bud limb development.

Subject 5: Chimio-enzymatic synthesis of oligosaccharides from Bacillus anthracis - Preparation of glycoconjugate vaccines against anthrax

Team:
Glycobiology

Supervisors:
Thesis Director: Cyrille GRANDJEAN (cyrille.grandjean@univ-nantes.fr / 33 (0)2 51 12 57 32)
Thesis co-supervisor: Franck DALIGAULT (franck.daligault@univ-nantes.fr / 33 (0)2 51 12 57 30)

Thesis project:
Carbohydrates play an essential role in host/pathogen recognition: Highly exposed at bacteria surface, they often are the target of the host protective immune response and, thus, some motifs can be part of vaccine formulations. The Laboratory aims at including a glycoconjugate valency to the less than optimal, currently licensed vaccines directed against Bacillus anthracis, the etiological agent of anthrax and the main bioterrorism threat. A hexasaccharide which forms the repeat unit of a polysaccharide {→6)-[beta-Galp-(1→4)]-[alpha-Galp-(1→3)]-alpha-GalpNAc-(1→4)-beta-ManpNAc-(1→4)-[alpha-Galp-(1→3)]-beta-GlcpNAc-(1→} and which is largely expressed by both the spores and the vegetative cells, respectively the infectious form and the form present in the host of the bacterium, appears as a potential candidate. Despite recent progress, total oligosaccharide synthesis is still considered as a limiting step to the development of semi-synthetic glycoconjugate vaccines. Therefore, we have planned to prepare this motif as well as fragments or analogs thereof according to novel chimio-enzymatic routes. Part of the project will consist in using and developing new enzymatic tools able to catalyze glycosylation reactions (use of glycosynthases, of glycosyl transferases obtained by mutagenesis and directed evolution). The antigenicity of the oligosaccharides will be assessed and the most promising candidates will be further conjugated to a protein of B. anthracis, used as a carrier, to evaluate their capacity at inducing an immune response in animal models (collaboration University of Strasbourg, University of Hohenheim - Germany).

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