PhD position OT-22075

PHD - Beyond Borders: Unraveling Virus-Microbiota Interactions and decoding the glycomic symphony

31076 TOULOUSE

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INRAE presentation

The French National Research Institute for Agriculture, Food, and Environment (INRAE) is a major player in research and innovation. It is a community of 12,000 people with 272 research, experimental research, and support units located in 18 regional centres throughout France. Internationally, INRAE is among the top research organisations in the agricultural and food sciences, plant and animal sciences, as well as in ecology and environmental science. It is the world’s leading research organisation specialising in agriculture, food and the environment. INRAE’s goal is to be a key player in the transitions necessary to address major global challenges. Faced with a growing world population, climate change, resource scarcity, and declining biodiversity, the Institute has a major role to play in building solutions and supporting the necessary acceleration of agricultural, food and environmental transitions.

Work environment, missions and activities

As a prospective PhD candidate, your academic voyage will lead you to the esteemed French National Research Institute for Agriculture, Food, and Environment (INRAE). This institution stands as a beacon of scientific excellence, driving innovation and advancing knowledge across disciplines. Your scholarly home will be the Host-pathogens interaction Unit (IHAP) at the renowned National Veterinary School of Toulouse (ENVT), nestled in the vibrant city of Toulouse. Here, you’ll find a stimulating environment where rigorous research meets academic rigor.

Within this dynamic context, you’ll collaborate closely with two pivotal teams: Myc and Viremie. The team MYC comprises seasoned experts in microbiota research, and delves into the intricate dialogue between host and microbiota. The Viremie team is part of the same IHAP research unit and focuses on host-virus interactions, and aims to unravel the mysteries of viral infections. As a PhD candidate, you’ll work alongside scientists, research technicians, and fellow PhD students, sharing insights and pushing the boundaries of knowledge.

 

Introduction: Bovine respiratory infectious diseases pose a significant health challenge for cattle, impacting both their well-being and overall health. This disease results from a complex interplay between bacterial and viral pathogens. In healthy animals, the respiratory tract’s mucus layer, containing mucins and a diverse microbial ecosystem, acts as a barrier to prevent pathogen invasion. However, viruses, especially, can exploit mucin glycans to infect the host. While current research highlights the critical role of the respiratory microbiome-glycome complex in colonization by pathogens, detailed information in animals remains limited.

Thesis Objectives: This thesis aims to unravel the intricate interactions among mucin glycans, the respiratory microbiome, infectious agents (including coronavirus (BCoV), influenza D virus (IDB), and Mycoplasma bovis), and animal health and welfare. Specifically, the project will focus on:

Virus-Glycan Interactions:

  • Investigating specific virus-glycan interactions in vitro and ex vivo during co-infection by BCoV and IDB.
  • Examining whether key mucin glycans play essential roles in other viruses, including those with zoonotic potential.
  • Validating these interactions through in vitro binding assays and immunohistochemistry on fixed tissue samples (lung explants).

Microbial Culturomics:

  • Developing and implementing culturomics on nasal samples to enrich, identify, and isolate bacteria with potential beneficial effects against pathogens.
  • Using culturomics as a basis for obtaining enzymes that will be subsequently tested in vitro against target viruses (in collaboration with the Norwegian Veterinary Institute).

Role of Microbial Enzymes:

  • Elucidating how microbial enzymes (e.g., proteases and sialidases) modulate viral infectivity.
  • Investigating how selected microbial enzymes can cleave viral fusion proteins and influence infection dynamics.

Methodology and Infrastructure: This research will leverage state-of-the-art facilities, including animal experimentation infrastructure at the ENVT, glycoconjugate analysis equipment at the Platform for Glycoconjugate Analysis (Pagés) in Lille (utilizing NMR and mass spectrometry), and sequencing platforms for microbiome data. Additionally, standard microbiology and cellular virology facilities will be used for culturomics, virus/protein production, and lung explant studies.

Expected Impact: The outcomes of this research may lead to the development of pro-, post-, and prebiotics aimed at enhancing calf respiratory barriers. Ultimately, this work could revolutionize prevention and management strategies for bovine infectious diseases, improving animal health and welfare.

 

The research program will be structured around 3 main axes:

  • Describe specific virus-glycan interactions in vitro and ex vivo and determine if the main mucin glycans during co-infection by IDV and BCoV are essential for other viruses, including those with zoonotic potential. The student will compare the list of sialic acids and glycoconjugates of interest identified by the glycomic approach with an in vitro binding test. Afterwards, they will perform immunohistochemistry (IHC) of glycans on fixed tissues (lung explants).
  • Develop and implement culturomics on nasal samples to enrich, identify, and isolate bacteria with potential beneficial action against pathogens. The culturomic approach will also form the basis for obtaining enzymes that will then be tested in vitro against the viruses of interest, thanks to protocols shared between IHAP and NVI (Norway).
  • Elucidate the role of microbial enzymes (e.g., proteases and sialidases) in modulating viral infectivity. This joint project will focus on studying how selected microbial proteases, sialidases, and esterases can cleave viral fusion proteins and influence infection.

 

The candidate will engage different collaborations throughout the research journey:

  • Interdisciplinary Collaboration: The candidate will be at the intersection of multiple scientific disciplines, requiring effective communication and collaboration with experts in virology, microbiology, glycomics, and animal health.
  • Academic and Research Community: They will be part of a vibrant academic community at the ENVT and INRAE, and will interact with various research groups, including those at the Glycoconjugate Analysis Platform in Lille and the Norwegian Veterinary Institute (NVI).
  • Mentorship and Guidance: The PhD student will receive mentorship from co-supervisors who are proficient in the methodologies to be used, providing an environment for learning and professional development.
  • Scientific Network: Engagement with national and international funding bodies, as well as participation in scientific conferences and seminars, will be crucial for networking and disseminating research findings.
  • Peer Interaction: Regular interactions with other PhD students, postdocs, and research technicians will form an essential part of the candidate’s daily work environment and peer support system.
  • Inter-Institutional Relations: The project involves cooperation between different national and international institutions, which will require the candidate to navigate and maintain productive relationships across organizational boundaries.

 

Training and skills

Master's degree/Engineering degree
  • Interdisciplinary Understanding: A comprehensive grasp of virology, microbiology, and glycomics, and the ability to synthesize these disciplines into a cohesive research approach.
  • Theoretical Foundations: Solid knowledge of the theoretical underpinnings of bacteriology and virology to inform experimental design and data interpretation.
  • Data Analysis Principles: Familiarity with bioinformatics, statistical methods, and data analysis techniques relevant to large datasets generated by sequencing and glycomic analyses
  • Laboratory Techniques: Familiarity in a range of laboratory molecular techniques and immunohistochemistry
  • Computational Proficiency: Computational skills to manage and analyze large datasets, including programming languages like R.
  • Collaborative Ability: Effective communication and teamwork skills to collaborate with diverse national and international research teams, adapting to various research cultures and expectations.

INRAE's life quality

By joining our teams, you benefit from (depending on the type of contract and its duration):

- up to 30 days of annual leave + 15 days "Reduction of Working Time" (for a full time);
parenting support: CESU childcare, leisure services;
- skills development systems: trainingcareer advise;
social support: advice and listening, social assistance and loans;
holiday and leisure services: holiday vouchers, accommodation at preferential rates;
sports and cultural activities;
- collective catering.

How to apply

I send my CV and my motivation letter

Offer reference

  • Contract: PhD position
  • Duration: 36 months
  • Beginning: 01/10/2024
  • Remuneration: 2,100€ gross monthly
  • Reference: OT-22075
  • Deadline: 08/07/2024
Centre Occitanie-Toulouse

L'UMR INRAE-ENVT 1225 Interactions Hôtes-Agents Pathogènes (IHAP) 31076 TOULOUSE

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