Description du sujet de thèse

A significant challenge in contemporary biology and medicine is unravelling the intricate interactions between genetic variation and environmental factors that influence developmental processes and disease susceptibility. This PhD project aims to address this challenge by characterizing the molecular aspects of genotype-environment interactions within the nematode germ stem cell system, regulated by the Delta-Notch pathway. The Delta-Notch pathway is a highly conserved genetic pathway implicated in various human pathologies. Our approach involves two primary objectives. First, we will molecularly examine the interplay between natural genetic variation and environmental factors to comprehend their modulation of stem cell niche activity. Second, we will introduce targeted mutations into a panel of diverse genetic backgrounds in order to identify new alleles influencing the penetrance and expressivity of these mutations, with a particular focus on variants capable of suppressing excessive germ cell proliferation. These experiments aim to offer novel insights into how natural molecular variation influences responses to environmental stimuli and mutations, specifically affecting the activity levels of a stem cell system governed by the Delta-Notch pathway. Consequently, this project will provide fundamental information on why certain individuals exhibit heightened sensitivity to environmental perturbations and how natural allelic variation can either suppress or enhance mutations with deleterious effects, such as uncontrolled cell proliferation.

Contexte de travail

Education & Academic Background:
Master's degree in evolutionary biology, genetics, molecular biology, developmental biology, or a related field.
Strong understanding of quantitative genetics, developmental biology, and bioinformatics.
Technical Skills:
Previous experience (or strong motivation to learn) working with Caenorhabditis elegans.
Proficiency in molecular genetics techniques: mutagenesis, cloning, PCR, CRISPR/Cas9, etc.
Microscopy skills, particularly for germline analysis.
Knowledge of statistical and bioinformatics tools for genetic data analysis.
Ability to manage high-throughput experiments, including with panels of diverse genetic strains.
Soft Skills:
Autonomy, scientific rigor, critical analytical thinking.
Enjoyment of collaborative work in an interdisciplinary team.
Strong scientific writing and communication skills.
Language:
Excellent command of English, both written and spoken (minimum B2 level, C1 recommended).
French is not required, but a willingness to integrate into a French-speaking environment is a plus.

Host Team
The PhD student will join the team led by Christian Braendle, titled "Gene-Environment Interactions in Development and Evolution".
This team is part of the Institut de Biologie Valrose (iBV) — a joint research unit CNRS / INSERM U1091 / Université Côte d'Azur.
http://ibv.unice.fr/research-team/braendle/
The lab is located in the heart of Parc Valrose, on the Science Faculty campus of Université Côte d'Azur in Nice (06100), France.

Contraintes et risques

- Laboratory activities requiring compliance with current hygiene and safety regulations.
- Handling of common reagents in a secure environment, following standardized protocols.
- Use of personal protective equipment (gloves, lab coat, goggles) required according to established procedures.