SCIENCE-JOBS-DE

PhD position (Heidelberg), "Immune-modulating nucleotide modifications within tRNA" (Heidelberg)

PhD position (65%)

available in the research group of Professor Dalpke

Dept. of Infectious Diseases - Medical Microbiology and Hygiene, University Heidelberg

“Immune-modulating nucleotide modifications within tRNA”

The innate immune system recognizes conserved, microbial structures including nucleic acids by pat¬tern recognition receptors.

Recognition of foreign, microbial nucleic acids is based on differences in sequences and structure, presence of nucleotide modifications and subcellular compartmentalization of the respective receptors. We recently showed that Toll-like receptor 7 (TLR7) not only recognizes single-stranded RNA but is also activated by bacterial tRNA. The decisive discrimination of bacterial versus host tRNA was due to the presence of an inhibitory 2’-O-methylation at guanosine 18 (Gm18).

Results on inhibitory modifications within the natural tRNA context were obtained by combining techniques in RNA synthesis and analysis with immunobiological assays. The newly developed techniques are now to be used to answer basic questions of RNA recognition by TLR7. It is intended to identify the molecular mechanism by which Gm18 suppresses an immune response. Therefore, positional effects and cellular signal transduction will be analyzed. Furthermore, new immune-modulating nucleotide modifications will be identified within bacterial and eukaryotic RNA using LC/MS and the recently developed synthesis of chimeric RNAs. Finally, functions of the identified nucleotide modifications with respect to foreign/self discrimination and a potential role for bacterial immune evasion will be studied.

The project will be done in close cooperation with the group of Prof. Mark Helm, Institute of Pharmacy and Biochemistry, University Mainz

who will contribute with expertise in RNA chemistry. Our group is applying a combination of immunological, biochemical and microbiological techniques. We offer an exciting interdisciplinary project in a stimulating and interactive environment at the world- renowned Heidelberg life sciences campus.

Start of PhD project: 1st of july 2014 (or later), funded by a 3-year DFG grant

Personal qualifications: Applicants should have a master degree in biology, biochemistry or pharmacy. They should have a strong interest in addressing basic immunological questions using methods from different fields. Ideally, candidates should have a background in both, immunology and biological chemistry. We are seeking for candidates with a high degree of motivation and curiosity, who are looking forward to interact with the members of our group and with the collaboration partner from chemistry.

Applications should be sent as one pdf file within two weeks after publication of this ad to Prof. Dr. A. Dalpke, Dept. of Hygiene and Medical Microbiology, University Hospital Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, phone +49 6221 56 38173, alexander.dalpke@med.uni-heidelberg.