Mots-Clés
genomics
software development
Pipeline
microbiology
benchmark
Description
Master Internship offer M2
Internship supervisors and host laboratory
Supervisor: Coluzzi Charles (Professeur Junior, Université de Lyon, charles.coluzzi@univ-lyon1.fr)
Host laboratory: Laboratoire de Biométrie et Biologie Evolutive (LBBE), 43 boulevard du 11 Novembre 1918, Villeurbanne https://lbbe.univ-lyon1.fr
Research project title:
Design and Benchmark of a Tool for Environmental Detection of Antibiotic-Resistance Plasmids
Project description:
Antimicrobial resistance (AMR) has emerged as one of the leading public health threats around the world. The spread of antimicrobial resistance can be largely attributed to the dissemination of antibiotic resistance genes (ARGs) through horizontal gene transfer, primarily mediated by plasmids. However, ARG-plasmids are not exclusive to pathogenic species. Non-pathogenic microbial communities serve as significant reservoirs for plasmids carrying ARGs, where they can persist even without antibiotic pressure [1]. In fact, many plasmid-mediated resistance genes in pathogens may originate from environmental, animal, or non-clinical human sources [2]. Therefore, the AMR crisis can only be tackled with a One Health approach [3].
Yet, despite evidence of plasmids mobilizing ARGs between these habitats, our understanding of the evolutionary mechanisms driving this process remains limited. Previous studies on the spread of ARG-plasmids have focused mainly on clinically relevant pathogenic bacteria in single isolate cultures [4]. However, tackling antibiotic resistance demands a global perspective. Therefore, it is essential to investigate the presence and evolution of these plasmids within metagenomes of various habitats.
Recent advancements in metagenomic approaches offer solutions to this challenge by providing a substantial number of metagenomes from various environments. However, existing methods still struggle to detect novel plasmids in metagenomes as they rely heavily on reference genome sequences. Put simply, the absence of universal genetic markers for plasmids limits current approaches from a complete understanding of plasmid diversity across different habitats.
The objective of this internship is to develop a computational tool to detect plasmids across different habitats. The tool will rely on the plasmid marker database already built in the laboratory [5]. We will focus on making it available and easy to use for the community: we will benchmark its accuracy, speed, and memory usage on metagenomic microbiomes and complete genomes ; and we will provide a simple installation and command-line interface. The final deliverable will be an open-source tool that is easy to use, fast, and precise, with clear documentation and example workflows. This will also prepare the ground for a PhD project on habitat-specific reservoirs of resistance plasmids and their contribution to environmental AMR dynamics.
Specific tasks
• Integrate the lab’s plasmid marker database.
• Develop the detection pipeline and calibrate decision rules. (scoring, thresholds, habitat-specific presets)
• Benchmark, tune, and release for the community (accuracy/speed, docs, container/Conda package, tests, example dataset).
What you will gain by joining us
By joining this project, you will benefit from training in bioinformatics and evolution:
• Robust software development skills
• Familiarization with big data
• Solid experience in comparative genomics and molecular microbiology
• Autonomy, rigor, and critical thinking
You will work in a stimulating research environment, surrounded by doctoral students, postdoctoral fellows, and interns; an enthusiastic and accessible supervisor (me) will guide you and share their energy with you. This internship will allow you to develop a solid scientific network and effectively prepare you for the next step in your career (thesis, bioindustry, R&D). It is possible to continue the project as a Phd.
Expected profile and skills of the candidate
The ideal candidate should have strong skills in bioinformatics/computer science and be willing to acquire extensive training in microbiology. They should have a genuine enthusiasm for science.
Laboratory publications or recommended review on the subject:
- Carroll, A.C. and A. Wong, Plasmid persistence: costs, benefits, and the plasmid paradox. Can J Microbiol, 2018. 64(5): p. 293-304.
- Matlock, W., et al., Enterobacterales plasmid sharing amongst human bloodstream infections, livestock, wastewater, and waterway niches in Oxfordshire, UK. Elife, 2023. 12.
- McEwen, S.A. and P.J. Collignon, Antimicrobial Resistance: a One Health Perspective. Microbiol Spectr, 2018. 6(2).
- Mughini-Gras, L., et al., Attributable sources of community-acquired carriage of Escherichia coli containing beta-lactam antibiotic resistance genes: a population-based modelling study. Lancet Planet Health, 2019. 3(8): p. e357-e369.
- Coluzzi, C. and E.P. Rocha, The spread of antibiotic resistance is driven by plasmids amongst the fastest evolving and of broadest host range. bioRxiv, 2024: p. 2024.07.23.604842.