Martin Luther University Halle-Wittenberg

The section Microbial Biotechnology (Institute of Biotechnology; Prof. Sven-Erik Behrens) at the Martin Luther University Halle-Wittenberg is seeking a highly motivated PhD student in the course of a research project funded by the German Research Foundation (DFG).

Background: Antisense procedures have long been in development, for therapeutic use in humans, and also for crop protection. They aim to inactivate (‘silence’) cellular or pathogenic target RNAs or to modulate their function. Central functional components are small nucleic acids (NAs) as small interfering RNAs (siRNAs) or antisense DNA-oligonucleotides (ASOs), which mostly direct endonucleases to the targets. Despite significant progress in the past years, antisense procedures still encounter considerable technical limitations. Due to their high structural complexity, it was yet impossible to reliably identify regions in target RNAs that are accessible for NAs and are referred here to as ‘accessible sites’ or a-sites. Consequently, the design of siRNA or ASO agents yet relied on uncertain in silico predictions or empirical tests.

We developed an experimental method, the ‘eNA screen’, which solved this problem. It is now possible to reliably identify in vitro (‘in the test tube’) siRNAs and ASOs that are capable to associate to a-sites of complex structured RNA molecules such as mRNAs or viral RNAs. In the plant system, we could show that thus identified siRNAs and ASOs effectively protect against viral infections. The eNA screen technology thus has the potential to significantly increase the potency and safety of antisense procedures.

In the proposed project, we will apply the eNA screen to two examples of human respiratory viruses, influenza A (FluvA) and respiratory syncytial virus (RSV). By exclusively using highly efficient eNAs, our long-term goal is to develop well-tolerated oral/nasal treatments against viruses for which little or no antiviral substances and/or vaccines are available. These could help to reduce the viral load in early stages of infection, inhibit viral spread and reduce the risk of severe disease progression and pandemics.

Most important publication

Gago-Zachert S, Schuck J, Weinholdt C, Knoblich M, Pantaleo V, Grosse I, Gursinsky T, Behrens S-E (2019). Highly efficacious antiviral protection of plants by small interfering RNAs identified in vitro. Nucleic Acids Res 47, 9343-9357.

Comment

https://www.sciencemag.org/news/2019/08/new-medicine-could-vaccinate-plants-against-devastating-viruses

Award

Hugo Junkers Preis 2018. 1st prize category Most Innovative Basic Research Project

Patent appl.

Schuck J, Gursinsky T, Behrens S-E (2018). Methode zur gezielten Identifizierung hocheffizienter small interfering RNAs „ERNAs“ zur Anwendung in Pflanzen und anderen Zielorganismen. PCT/DE2018/000194

 

Your qualifications: MSc. or Diploma in Biochemistry, Biology or Pharmacy. Experience in molecular biology/cloning and RNA handling.

Our expectations: You will perform eNA screens, RNA structure determinations of target RNAs, characterizations of esiRNAs and eASO in vitro, in infectious cell culture and in animal challenge experiments. Throughout your PhD thesis studies, you will closely work together with a highly experienced staff scientist. English is our common language.

Salary will be in accordance with German TV-L (0.65 E13) 36 months, 100% standard working time

Submit an application including your detailed CV, a letter describing your motivation, so far lab experience and contact information of three peers willing to provide references.

Um dich für diesen Job zu bewerben, besuche bitte biochemtech.uni-halle.de.