PhD position - Uncovering novel drug targets of polyprotein precursors of SARS-CoV2

Context & Job description

You will be joining the ESRF Structural Biology (SB) group that currently operates 8 end-stations for Structural Biology providing a wide range of state-of-the-art facilities for experiments in macromolecular crystallography (MX), BioSAXS and cryo-electron microscopy (cryo-EM).

The aim of the PhD project is to perform structural and functional studies on SARS-CoV2 non-structural protein 3 (Nsp3) domains and to exploit them for fragment screening campaigns in collaboration with the pharma company NUVISAN ICB GmbH, to identify lead compounds. Nsp3 protein from SARS-CoV2 plays a crucial role in viral replication and polyprotein processing and therefore is a vital therapeutic target. Nsp3 is the largest protein of the entire coronavirus genome and contains at least 15 different functional domains. The main goal for the PhD project is to target the papain-like protease and the domains upstream to it in a polyprotein context.

You will participate in the protein production and biochemical/biophysical  characterisation followed by structural studies using an integrated approach including X-ray crystallography, SANS and if applicable, cryo-EM. The results from this project will yield valuable insights into SARS-CoV2 therapeutics.

Further information can be obtained from Eaazhisai Kandiah (tel.: +33 (0)476 88 2691, email: eaazhisai.kandiah@esrf.fr) and from Christoph Mueller-Dieckmann (tel.: +33 (0)476 88 2870, email: christoph.mueller_dieckmann@esrf.fr) and Roman Hillig, (tel: + 49 30 468 18451, email: roman.hillig@nuvisan.com).

Expected profile

  • Degree allowing enrolment for a PhD (such as MSc, Master 2 de Recherche, Laurea or equivalent) in biology, biochemistry or closely related science
  • A background in molecular biology and protein biochemistry is essential and knowledge in X-ray crystallography, especially hands-on experience with crystallization and data processing will be an advantage. Basic knowledge in cryo-EM is an asset.
  • Proficiency in English (A proof of upper-intermediate level would be advantageous and can be provided in the application. Applicants originating from native-English-speaking countries can apply without the need for proof of level. An official degree conducted in English will be also accepted as a proof; Students without proof upper-intermediate level may still apply and their level of English will be checked during the interview).
  • Compliance with the Marie Sklodowska-Curie mobility rule: candidates may not have resided or carried out their main activity (work, studies, etc.) in France for more than twelve months in the three years immediately before the date of recruitment.
  • At the date of recruitment, early-stage researchers must be in the first four years of their research careers and have not yet been awarded a doctoral degree.
  • Candidates must satisfy eligibility criteria according to the partner university requirements for PhD enrolment.

More details about the application procedure on www.innovaxn.eu/for-students/documents/

Working conditions

The successful candidate will be enrolled in the doctoral school of Chemistry and Life Sciences of the University of Grenoble Alpes and based full-time at the ESRF (Grenoble, France), other than a 3-month secondment to the Company NUVISAN ICB GmbH (Berlin, Germany). In addition to the tuition/training for the skills required for the implementation of the PhD project, a varied pedagogical training program will be offered to the successful candidate throughout the 3-year PhD project.

More details on the InnovaXN program on www.innovaxn.eu

Company description

InnovaXN is a Horizon 2020 MSCA COFUND programme providing an opportunity for 40 industrial companies to work with 40 PhD students, performing advanced research and exploiting the unique characterisation techniques of the ESRF and ILL. Through collaborations with industry, innovation will be the central theme of the programme. This will provide a unique cross academic-industry science setting, secondment opportunities and society-relevant research, training the future key researchers able to tackle major research and societal challenges.

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