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Reference : UPR9002-ROLMAR-002
Workplace : STRASBOURG,STRASBOURG
Date of publication : Friday, September 25, 2020
Scientific Responsible name : Roland Marquet et Laurence Despons
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 February 2021
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Influenza A viruses are responsible for seasonal flu epidemics and occasional flu pandemics. Their genome consisting of eight segments of genomic RNA (vRNAs) of negative polarity allows rapid evolution, named antigenic shift, by genetic reassortment of the vRNAs of two influenza A viruses infecting the same cell. This process generates new influenza A viruses with high pandemic potential. However, this evolutionary advantage complicates packaging of the viral genome, as the viral particles must contain one copy of each vRNA in order to be infectious. It is generally accepted that each vRNA is selectively packaged as a viral ribonucleoprotein (vRNP, in which the vRNA is associated with trimeric polymerase and multiple copies of the nucleoprotein (N)). Each vRNA indeed contains specific packaging signals, and an increasing number of publications support the existence of direct base-pairing interactions between vRNAs.
Genetic reassortment between divergent influenza A viruses is a strongly biased process, as only a small number of the 254 theoretically possible genotypes are efficiently produced. This restriction is due to the limited compatibility between the packaging signals of divergent influenza A viruses and to the limited conservation of the interactions between the vRNAs that are required for optimal packaging. Thus, analysis of genetic reassortment not only shed light on the molecular mechanisms by which reassortant viruses are produced, but also on the mechanisms allowing the coordinated packaging of the segmented genome of influenza A viruses.
The PhD thesis project aims at studying the secondary structure of the vRNA in parental and reassortant viruses using chemical probing, namely SHAPE-MaP. This analysis should allow to identify differences in the vRNA-vRNA interactions between parental and reassortant viruses. This data will be used to identify packaging signals using bioinformatics, and these predictions will be tested experimentally. Finally, compounds designed to selectively interfere with vRNA-vRNA interactions will be generated.
This Early Stage Researcher (ESR) position (PhD fellowship) in molecular and structural virology is part of the VIROINF (Understanding (harmful) virus-host interactions by linking virology and bioinformatics) project, which opens a total of 15 ESR positions (the full list of positions is available here: https://viroinf.eu/apply/). VIROINF is a European Training Network (ETN) funded by European Commission under the Horizon 2020 Marie Sklodowska-Curie Action.
This PhD project will be mainly performed within the 'Viral Ribonucleoprotein, genome packaging, and viral assembly' team led by Roland Marquet and Jean Christophe Paillart, which consist of about 12 people, under the supervision of Roland Marquet and in collaboration with Laurence Despons for bioinformatics. This team is part of the CNRS Unit UPR 9002 ARN, headed by Pascale Romby, which studies RNA functions under normal and pathologic conditions, including infections by viruses, bacteria and parasites. The UPR 9002 ARN Unit is part of the Institut de Biologie Moléculaire et Cellulaire, in Strasbourg, France.
The PhD project includes several secondments (for a total of about 10 months) in Germany (Freiburg, Jena) and Austria (Vienna).
Constraints and risks
Please see below the eligibility criteria, how to apply, and the salary details.
European and non-European students (M/F) are eligible
To be eligible, the candidate (M/F):
- must be in the first four years of her/his research career. Candidates should ideally possess a Master's degree in an academic field relevant to the PhD project, or a degree that allows them to embark in a PhD at the University of Strasbourg. (Applications from candidates who already possess a doctoral degree cannot be considered)
- must not have resided or carried out their main activity (work, studies, ect.) in France for more than 12 months in the 3 years immediately before the recruitment date. Short stays such as holidays and/or compulsory national service are not taken into account.
- be willing to spend a prolonged time in other institutes/countries of the network during the PhD thesis period
- have great interest and be willing to work at the interphase of two disciplines
How to apply
In order to fulfill the requirements of both the CNRS and VIROINF ETN, the candidate (H/F) havs to apply in parallel both:
-on the 'emploi.cnrs.fr' website
- by sending an email to email@example.com, till the 30th of October 2020. The mail subject has to be ESR-VIROINF, please include a letter of interest, a CV and at least one recommendation letter as one pdf file (max file size 5 MB).
October 2020: Online applications
November 2020: Interviews of the selected candidates (probably only via online systems)
1st December 2020: Communication of the final selection
1st February 2021– 1st April 2021: Recruitment
The selected candidate (M/F) will receive a living allowance, a mobility allowance, and if eligible a family allowance. The monthly brut salary will be about 2840 € without family allowance, or if eligible, about 3150 € with family allowance.
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