Description du sujet de thèse

Dengue (DENV) and Zika (ZIKV) viruses are transmitted by mosquitoes of genus Aedes. DENV and ZIKV belong to the Flaviviridae family like the Yellow fever virus (YFV) and West Nile virus (WNV). Dengue virus is the most significant arthropod-borne viral pathogen in humans with 400 million infections annually, about 5% of the world's population. DENV is usually asymptomatic or produces a wide range of symptoms like high fever, muscle and joint pain, nausea, headache, skin rash, … Regarding ZIKV, it was a relatively obscure pathogen until 2007, when it started causing outbreaks in Pacific islands and later in the Americas, with a massive outbreak in Brazil in 2015-2016. Several congenital injuries, like ocular lesions and microcephaly, and/or neurological disorders have been observed. Currently, no efficient treatments or vaccines are available against these viruses. Considering that DENV and ZIKV circulate in both vertebrate and invertebrate hosts, targeting specific steps of viral replication would be an efficient strategy to block viral transmission and disease spread. The development of new drugs requires a precise understanding of each step of the viral replication cycle. RNAs are now recognized as valuable targets for the development of new drugs. Several RNA structures within untranslated regions (5'- and 3'-UTR) of genomes from DENV and ZIKV have been identified as essential for viral replication and for hijacking host's cellular machinery.
The thesis project will focus on the characterization of mosquito protein factors interacting with the non-coding regions of ZIKV/DENV viral RNA, and of viral RNA/protein complexes involved in DENV and ZIKV replication cycle. Several complementary biophysical approaches will be used: microcalorimetry, mass spectrometry, Crystallography, Nuclear Magnetic Resonance, etc.. This study will contribute to finely characterize mechanisms driving the viral replication and will provide basis for the design of new drugs that would interfere with the viral replication cycle.

Contexte de travail

The IBMC institute is located in the heart of the campus of the University of Strasbourg, easily accessible by bus and tram. The Unit “RNA architecture and reactivity”, under the supervision of CNRS (UPR 9002) is a multidisciplinary laboratory which research themes are focused on the RNA biology of the RNA world. The Unit is structured into 12 groups and has a total staff of 117 staff including 59 permanent staff (ie 25 CNRS researchers, 12 teachers/researchers, 2 INSERM researchers, 19 CNRS engineers and technicians and 1 unistra technician), 4 emeritus researchers, 21 staff on fixed-term contracts and 33 doctoral students M/F.
The PhD student will be welcomed within the “Structure and dynamics of biomolecular machines” Team which is composed of 6 researchers, 4 engineers, 1 post-doctoral researcher and 2 doctoral students.
The PhD student will be attached to the Doctoral School of Life Sciences and Health (ED414).
The PhD student will be able to benefit from all materials conditions (instrumentation, equipped laboratory), human support (sharing of expertise) and informatic necessary for the successful completion of the thesis project.
The candidate will benefit from access to an administrative restaurant, partial reimbursement of travel expenses and a work council.
The candidate must hold a Master's and/or engineering degree.
He/She will need to prove a solid knowledge in RNAs and proteins biochemistry, and in Biophysics. A strong interest in bioinformatic and data processing will be an advantage.
The candidate must be fluent in English in writing and orally (at level C2 according to the Common European Framework and reference for Languages) in order to be able to write reports and to present results at meetings and conferences.
Applications should include a detailed CV, two references, a letter of motivation, a summary of the Master's internship, as well as the grade of Master 1 and 2.

Contraintes et risques

Casual travels at NMR and Crystallographic platforms located outside the Unit. The costs are covered by the laboratory.