PhD Position – Regulation and Functional Role of FGF23 in Chronic Inflammatory Diseases

Scientific Background

Chronic inflammatory diseases represent a major public health issue, affecting multiple organs as well as the circulatory system as a whole. Fibroblast Growth Factor 23 (FGF23) is a key hormone produced by the bones and involved in ion metabolism, particularly phosphate and iron homeostasis. FGF23 is regulated by inflammation and has emerged as a major contributor to the development of cardiovascular disorders (CVD).

FGF23 is known to undergo post-translational cleavage; however, the biological impact of this cleavage and the potential roles of the resulting peptide fragments remain largely unknown in the context of chronic inflammatory diseases.

Objectives

The aim of this PhD project is to investigate the transcriptional and post-translational modifications of FGF23 in vitro, in vivo, and in patients with inflammatory diseases.

Research Plan

The project is structured around three main objectives:

1. Identification of FGF23 sources during inflammation
   We will characterize the relative contributions of key organs and cell types to FGF23 production under inflammatory conditions, using multi-omics approaches.
2. Characterization of transcriptional and post-translational modifications
   We will investigate transcriptional regulation and post-translational processing of FGF23 to generate a detailed map of the molecular changes occurring during hormone synthesis.
3. Functional analysis of FGF23 peptides
   We will assess the respective effects of the different molecular forms of FGF23 on the immune system and on the development of cardiovascular disorders.

Each of these three axes will be supported by complementary cellular approaches, animal models, and analyses of patients’ samples.

Expected Outcomes

This project will provide new insights into the pathophysiological mechanisms governing phosphate and iron regulation in chronic inflammatory diseases and may open new therapeutic perspectives.

The research department is SAINBIOSE (U1059), located on the Campus Santé in Saint-Etienne (Université Jean Monnet, INSERM, and École des Mines).

The laboratory comprises approximately 150 members and focuses primarily on multi-scale approaches to osteoarticular and cardiovascular diseases.

Applicants should hold a Master, or equivalent, in biomedical sciences (physiology, cellular and molecular biology, immunology, or related fields).

The ideal candidate will demonstrate a strong interest in translational medical research, solid knowledge of integrative physiology and inflammation, ability to critically analyze and synthesize scientific literature, scientific writing skills, experience in some of the following techniques: cell and molecular biology, histology, biochemistry, microscopy…The project includes preclinical animal models. Transversal skills in statistics and English are expected. An international mobility of several weeks during the PhD is considered.