PhD candidate in epigenetics (M/F)

Job Description

Thesis Subject

DNA methylation is an epigenetic mark with multiple functions in genome regulation. It is catalyzed by DNA methyltransferases (DNMTs) and consists of the addition of a methyl group (-CH₃) to cytosine, generating the modified base 5-methylcytosine (5mC). In humans, dysregulation of DNA methylation is associated with numerous diseases. In particular, mutations in the DNMT3A gene cause Tatton-Brown-Rahman syndrome (TBRS, OMIM #615879), a neurodevelopmental disorder characterized by intellectual disability, psychiatric manifestations, and autism spectrum disorder (Tatton-Brown et al., 2018). A better understanding of the molecular etiology of these disorders is essential for the development of future therapeutic strategies. The aim of the PhD project is to use cerebral organoid models to investigate the role of DNMT3A in normal and pathological human brain development. The candidate will validate hiPSC clones carrying DNMT3A mutations and generate cerebral organoids from both wild-type and mutant hiPSC lines. Organoid phenotypes will be analyzed at multiple developmental stages using immunostaining and imaging approaches. In parallel, organoids will be characterized at the transcriptomic (RT-qPCR and single-cell RNA sequencing) and epigenomic levels by generating genome-wide DNA methylation maps. Phenotypic and molecular datasets will be integrated to link DNA methylation changes with alterations in gene expression and cellular trajectories. The combined analysis of gene expression, DNA methylation, and organoid phenotypes will provide insight into the cellular programs and biological functions disrupted by DNMT3A mutations. The findings will advance our understanding of the role of DNA methylation in human brain development and shed light on the molecular mechanisms underlying DNMT3A-associated neurodevelopmental disorders.

Required qualifications:
-Master's degree in Molecular Biology, Genetics, or Developmental Biology
-Laboratory experience in epigenetics and human stem cells/organoids

Your Work Environment

The laboratory Biotechnology and Cell Signaling (UMR 7242, CNRS/University of Strasbourg) is located on the campus of the École Supérieure de Biotechnologie de Strasbourg (ESBS) in Illkirch, France. The unit comprises approximately 110 researchers, engineers, technicians, and students conducting research on cellular signaling pathways and the development of innovative therapeutic strategies.
Research unit website: https://bsc.unistra.fr

The candidate will join the team “Epigenetic Regulation of Cell Identity”, which consists of 10 members and investigates the role of DNA methylation in normal and diseased cells. The candidate will be supervised by Michael Weber. The team has extensive expertise in molecular and genetic approaches and provides access to state-of-the-art technological platforms required for the project. The candidate will receive training and supervision in genome editing (CRISPR/Cas9), cerebral organoid generation, epigenetic profiling technologies, and bioinformatic analysis of high-throughput sequencing datasets, including transcriptomic and DNA methylation (methylome) data.

The candidate will benefit from:
-Easy access to the laboratory via the Tram network.
-Access to a CROUS university restaurant located on campus.
-Reimbursement of up to 75% of public transportation costs, and a sustainable mobility allowance of up to €300 per year, subject to eligibility.
-Employee benefits, including partial health insurance coverage and access to the Social Welfare Committee (sports, leisure activities, cultural events, discounted ticketing).

Constraints and risks

No specific constraints or risks.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

The research professions