DESCRIPTION
Engineering Hyper-Recombinogenic Streptomyces Strains for Biosynthetic Pathway Diversification and Discovery of Novel Bioactive Molecules
Project: DIAMS (Diversification of the Specialized Metabolite Synthesis Arsenal in Streptomyces via Recombination Modulation)
Project Background
The discovery of new bioactive molecules remains a major challenge for addressing emerging needs in human health, biotechnology, and sustainable industrial processes. Members of the genus Streptomyces are among the most prolific producers of specialized metabolites, including antibiotics, anticancer agents, immunosuppressants, and industrially relevant enzymes.
Recent genomic studies have revealed that Streptomyces genomes harbor up to 40 biosynthetic gene clusters (BGCs), many of which remain cryptic or poorly characterized. In parallel, recent work from our laboratory demonstrated that conjugation-mediated large-scale chromosomal transfer can generate extensive genomic mosaics and hybrid BGCs, providing a natural mechanism for metabolic diversification.
We have also identified the DNA repair endonuclease NucS, which generates DNA double-strand breaks (DSBs) and plays a key role in genome dynamics and recombination. The DIAMS project aims to exploit NucS-mediated recombination to create hyper-recombinogenic strains capable of accelerating the evolution of biosynthetic pathways and generating novel bioactive compounds.
Research Objectives
The successful candidate will contribute to the development and characterization of engineered Streptomyces strains with enhanced recombination capacity.
The main objectives include:
- Investigating the molecular mechanisms involved in NucS-dependent DNA double-strand break repair.
- Identifying cellular factors interacting with NucS and determining their role in recombination control during horizontal gene transfer
- Constructing and characterizing hyper-recombinogenic chassis strains.
- Generating recombinant strains through conjugation between environmental Streptomyces isolates.
- Identifying hybrid biosynthetic gene clusters through genome sequencing.
- Evaluating the metabolic consequences of BGC hybridization using non-targeted metabolomics.
- Contributing to the discovery of novel specialized metabolites with potential biotechnological applications.
Research Activities
Microbial Genetics and Molecular Biology
- Genetic manipulation of Streptomyces strains.
- Construction of mutants and engineered strains.
- Conjugation experiments and recombinant strain generation.
- Analysis of DNA repair and recombination pathways.
- Standard molecular biology techniques.
Genomics
- Genomic DNA preparation.
- Whole-genome sequencing (Illumina and/or Oxford Nanopore technologies).
- Analysis of chromosomal recombination events.
- Identification and annotation of biosynthetic gene clusters using antiSMASH and related tools.
Metabolomics
In collaboration with the PASM (Structural Analysis and Metabolomics Platform, University of Lorraine):
- Non-targeted metabolomics by high-resolution mass spectrometry (HRMS).
- Orbitrap ID-X and Q-TOF analyses.
- MS/MS-based molecular annotation.
- Molecular networking and metabolite discovery using the ASIA platform.
Bioinformatics and Data Analysis
- Analysis of genomic and metabolomic datasets.
- Statistical analysis and multivariate approaches.
- Comparative genomics.
Candidate Profile
Required Qualifications
- PhD in Microbiology, Molecular Biology, Genetics, Biotechnology, Genomics, or a related discipline.
Desired Expertise
Experience in one or more of the following areas is highly desirable:
- Bacterial genetics.
- Actinobacteria and/or Streptomyces biology.
- DNA repair and homologous recombination.
- Comparative genomics.
- Metabolomics and mass spectrometry.
- Bioinformatics and omics data analysis.
Experience with Linux environments and programming languages such as R or Python will be considered an asset.
Personal Skills
- Scientific curiosity and creativity.
- Ability to work independently.
- Strong analytical and problem-solving skills.
- Excellent communication and scientific writing abilities.
- Capacity to work within interdisciplinary and collaborative projects.
TERMS AND TENURE
Research Environment
The position will be based in the DynAMic Laboratory at the University of Lorraine (Nancy, France), within a highly collaborative environment combining microbial genetics, genome evolution, biotechnology, and natural product discovery. Some mobility (fully funded) within collaboratoring partners of the European GRASP project focused on DNA repair and antimicrobial resistance is expected mid-2027.
The postdoctoral researcher will interact closely with:
- The DynAMic research group.
- The PASM Metabolomics Platform.
- The ASIA analytical platform.
- International collaborators involved in the European GRASP project
The candidate will have access to state-of-the-art facilities in genomics, metabolomics, and bioinformatics.
The target start date for the position is October 2026, with some flexibility on the exact start date.
SALARY
Grossly monthly salary starting from 2000 €, depending on experience
HOW TO APPLY
Applicants are requested to submit the following materials:
• A cover letter applying for the position
• Full CV and list of publications
• Academic transcripts (unofficial versions are fine)
Deadline for application is August 30th 2026. Applicants will be interviewed by an Ad Hoc Commission (date to follow).
Applications are only accepted through email. All document must be sent to:
Dr Claire BERTRAND
[email protected]
JOB LOCATION
Nancy, Lorraine, France
