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Microbiologie & Sciences Humaines

Equipe n°10: Christelle Desnues, CR CNRS

EQUIPE EMERGENTE PATHOVIROME

https://pathovirome.wordpress.com/

 

Team Composition

 

1. Christelle DESNUES, CR1 (researcher)

2. Laura Fancello, étudiante en these (PhD student)

3. Sonia MONTEIL, Ingénieure d’étude (research assistant)

4. Thi Anh Dao Phung, stagiaire master 2, (master student)

5. Nikolay Popgeorgiev, Post-Doctorant (post-doc fellow)

6. Sarah Temmam, Ingénieure de recherche (research assistant)

 

Research context

 

While viral infections create an important threat for humanity, our knowledge of the viruses that infect humans is largely incomplete. So far, discovery of new viruses has been limited by the inability to propagate them in cell culture, the lack of serological cross-reactivity, or the absence of conserved genetic element that could be used for PCR-based analyses. Thus, numerous acute and chronic diseases with unknown etiology are caused by yet unidentified viruses. Among the highest failure rates in determining the etiological cause of disease, pneumonia, encephalitis, and pericarditis are usually cited. In these cases, the search for unknown viruses is an urgent scientific task. Our team aims at a better understanding and thus an improved diagnostic of idiopathic pathologies such as encephalitis, pneumonia, or pericarditis by characterizing new or divergent viral agents using a combination of high-throughput sequencing, culturing, and epidemiological studies.  

 

1. Team achievements

  

This team was created with the support of a Starting Grant from the European Research Council. The project is led by Christelle Desnues, a young researcher, bronze medal of the CNRS in 2010. This team fulfills an urgent need to develop and apply metagenomics and new sequencing tools in the medical context and particularly fits with the URMITE UMR 7278 research area. This team has a multi-disciplinary core (virology, bioinformatics) and actively interacts with the medical staff and the other teams of the laboratory.

 

2. Detailed research objectives


Metagenomics, the sequenced-based analysis of the whole collection of genomes directly isolated from a sample overcomes the main limitations of classical tools for viral detection. Indeed, unlike traditional techniques for virus identification, metagenomics bypasses the “single-organism-level” point of view of clinical diagnostics and thus the need to isolate and culture the targeted organism. Metagenomic application is therefore particularly appropriate for pathologies with a large number of idiopathic cases.

Basically, our researches follow three main axes:

 

Research axis 1: Characterization of the viral communities in healthy and diseased human samples.

Our first research axis is to characterize the human virome in different human samples. In order to have a big picture of “who is there”, we analyze the viruses at the community level. We use microscopy (epifluorescence and electron microscopy) to determine the viral abundances along with sequencing, bioinformatics, and mathematical modeling to define the viral diversity of each sample in terms of specific richness and evenness. 

 

Research axis 2: Identification of new viruses involved in pathologies

Our 2nd research axis is to identify new RNA and DNA viruses in human samples from patients presenting acute diseases and for which the diagnosis is currently incomplete. For this purpose, comparative metagenomics of control and patients with disease are used. 

 

Research axis 3: Epidemiological studies

Once a new or highly divergent virus is detected, a screening of a large number of samples allows the determination of the prevalence, abundance, and geographical distribution of the novel viruses.

 

3. Methodology


Patients are recruited from the cardiology, neurology and lung services of the Timone, Hôpital Nord and Sainte Marguerite hospitals, Marseille, France. Samples are sent to our laboratory for diagnostic purposes. Specimens are collected within a “diagnosis kit” which includes a consent form. No specimen is specifically done for the needs of the study and specimens are anonymous. Controls consist of patients with non-infectious diseases. Viral particles are usually purified by density gradient centrifugation and non-particle nucleic acids are removed using nucleases.  Viral DNA and RNA are then extracted and pyrosequenced on a Roche/454 GS-FLX machine.   

4. Implementation

 

1. Human resources

One of the forces of our research is association of clinicians and scientists under a same objective: a better knowledge on the causal agents of idiopathic pathologies. Currently, our team is composed of 6 persons: 1 post-doc, 1 research engineer, 1 research assistant, 2 PhD students and 1 undergraduate.

 

More details on team members are found here.

 

2. Interactions with other teams

The work we are carry-on meets an urgent need in the medical field. Our team thus has numerous interactions with the different hospital services and the other teams of the foundation. More particularly, we have strong interactions with the “Rickettsies and pathogènes émergents” (Pr. D. Raoult), “Microbiogénomique” (Pr. PE. Fournier), “Microorganismes de l’environnement et amibes” (Pr. Lascola), “Maladies émergentes et moustiques” (Pr. C. Rogier), “Résistances bactériennes, infections respiratoires et mucoviscidoses” (Pr. JM. Rolain) teams.

We also actively develop contractual and non-contractual collaborations with national and international partners resulting in public (EC2CO, INSU CNRS) and private (Total Foundation) fundings.

 

3. Infrastructure and equipment

Our research projects rely on the Méditerranée Infection platforms (link


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