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Regulators of sirtuin of type 1 (Sirt1): a key player in bone marrow adiposity increase in energy deficit context

ABG-83721 Thesis topic
2019-03-15 > €25,000 and < €35,000 annual gross
Université du littoral côte d'opale
Boulogne sur mer - Les Hauts de France - France
Regulators of sirtuin of type 1 (Sirt1): a key player in bone marrow adiposity increase in energy deficit context
  • Biology
Sirt1, osteoblast, bone marrow adiposity, anorexia nervosa, bone marrow stromal cell, epigenetic modifications

Description

PMOI (Physiopathology and inflammatory bone diseases) is the only European laboratory focused on the study of the relationship between bone marrow adiposity and bone physiology. It is strongly involved in a European network dedicated to this subject. The proposed project is one of its priority areas. The sirtuin of type 1 (Sirt1), a histone deacetylase (HDAC), which have pro- osteoblastic and anti-adipogenic effects by deacetylating lysine residues of key regulators and their cofactors implicated in differentiation pathways. In a mouse model of energy deficit mimicking consequences of anorexia nervosa (SBA model), we have highlighted, in vitro,  a sustainable down-regulation of Sirt1 expression in bone marrow stromal cells of anorectic mice compared to control mice. In vitro, this was accompagnied by an increase of adipogenesis at the expense of osteogenesis. Thus, we hypothesis in this thesis project that decrease of Sirt1 expression in bone marrow could be due to epigenetic modifications of Sirt1 promoter. Therefore, the main objective of this project is to identify these changes and to determine the molecular mechanisms responsible for Sirt1 down-regulation in SBA model. This will provide in a short term a better understanding of bone marrow adiposity’s regulation and in a medium term will allow to propose new therapeutic strategies to improve bone quality in osteoporosis related to anorexia nervosa.

The project will be carried out in collaboration with a team located in Lille and having a great expertise in epigenetic studies. The supervisors use routinely all the models and techniques necessary for the project.

Funding category

Public funding alone (i.e. government, region, European, international organization research grant)

Funding further details

50 % grants from Université du Littoral Côte d'Opale and 50% from Région Hauts de France

Presentation of host institution and host laboratory

Université du littoral côte d'opale

PMOI Lab is located on the sites:université de chirurgie dentaire Lille and the université du littoral Côte d'opale in Boulogne sur mer (62200). The principal theme of the lab is to study the interactions between osteoblasts and adipocytes in the bone marrow.

PhD title

Doctorat en Biologie cellulaire et moléculaire

Country where you obtained your PhD

France

Institution awarding doctoral degree

Université du littoral Côte d'Opale

Graduate school

Ecole Doctorale de Biologie et Santé de Lille

Candidate's profile

Required Skills :

- good experience in cell culture

- good experience in RNA extraction and gene expression analysis by real time PCR

- good knowledge of English

- good experience in epigenetic study would be appreciated

- be able to analyze the bibliographical and experimental data and to report on the results

 

Application deadline

2019-04-15
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