Přehled

Group:

Cryogenic Electron Microscopy

Tutor:

Mgr. Tomáš Kouba, PhD.

Field of study:

Biochemistry, molecular biology, structural biology, virology

Abstract:

Effective treatment against influenza viruses (Flu) suffers from virus resistance. Therefore, there is a great demand for exploring new drug targets and developing effective novel antivirals. This is challenging, since there is only a limited number of antiviral targets for rational drug design. This project will tackle both; it will explore and verify a new target and develop inhibitors against it. Cutting edge results in structural biology of the influenza RNA-dependent RNA polymerase (FluPol), identified a common general mechanism of Flu RNA transcription and replication cycle. The mechanism is entirely dependent on binding of viral endogenous RNA molecules to specific sites on the FluPol. Aided by already existing cryo-EM structures of FluPol, we will design inhibitors based on the sequence, atomic structure and interactions with the protein, and add extensive chemical modification to these viral RNAs. We will then test whether they can inhibit FluPol by in vitro and in cell-based experiments. Targeting these RNA binding sites and using RNA-scaffold based molecules is an innovative concept and expected to be robust in respect to the development of viral resistance. Altogether, the approach has great potential to bring a new universal paradigm to the field of antiviral drug discovery.

References:

University:

Faculty of Food and Biochemical Technology, UCT Prague; Faculty of Science, Charles University

How to apply:

At the Institute of Organic Chemistry and Biochemistry of the CAS / IOCB Prague, we are looking for talented, independent, and highly motivated PhD students with an MSc. degree or equivalent in life sciences or related fields. We are offering more than 20 new exciting projects in organic and medicinal chemistry, biochemistry, molecular biology, analytical, and physical chemistry.

  • Online registration deadline: 3 March 2024
  • Interview Day: 21 March 2024

Learn more and apply at www.uochb.cz/en/call-for-phd-applications.