Science jobs from Freie Universitaet Berlin;
Charité - Universitaetsmedizin Berlin:
Charité - Universitaetsmedizin Berlin:
· Post: Post Doc
· No of Position: 2
· Employer: Freie Universitaet Berlin; Charité - Universitaetsmedizin Berlin
· Location: Berlin, Germany
· Last date to apply: September 01, 2010
We are looking for 2 excellently qualified post-docs for a period of 2 years only, to work on the following projects.
Project 1: Polymorphisms in the mutS-rpoS genomic region of extraintestinal pathogenic Escherichia coli (ExPEC) - filling the gap between molecular and functional epidemiology
State of the art: Aside from harmless commensal strains, E. coli can be broadly categorized as intestinal and extraintestinal pathogenic E. coli (ExPEC), both being of immense medical and economic importance. ExPEC represent a versatile group of bacteria causing a number of diseases in humans and animals, e.g. urinary tract infections, septicemia, and meningitis. The high species diversity hampers a sound risk assessment of single strains concerning their virulence, host specificity, and zoonotic potential. Thus, it would be of immense value to implement an epidemiological study driven by Indian and German researchers to identify a global genetic marker enabling an “in vivo pathogenicity” categorization of the mixed population of E. coli. By that, it might be possible not only to predict human and animal health risk but also to unravel features contributing to the “reservoir life style” of different pathogen categories of ExPEC in the mammalian intestine and possibly to host specificity.
Previous work: Initial screening of a genomic region, anchored by genes mutS and rpoS, encoding a DNA mismatch repair system and the alternative sigma factor, respectively, revealed high levels of variation among human and animal ExPEC and commensal E. coli. Own initial data give clear evidence for a correlation of the mutS-rpoS intergenic region with the phylotype of the strains, their virulence gene profile, and most importantly, their in vivo pathogenicity, as tested in a systemic chicken infection model. In addition, mutS and rpoS knock-out mutants of a highly virulent avian ExPEC strain indicated regulatory roles for well known virulence factors and an influence on in vitro adhesion and in vivo pathogenicity.
Working hypothesis and work plan: The E. coli mutS-rpoS genomic region is (i) a future typing tool of ExPEC, (ii) a regulatory component of vital importance for their lifestyle (iii) a predictor of in vivo virulence, and (iv) a genetic marker for host specificity. We will systematically categorize human and animal isolates from India and Germany with regard to their affiliation to distinct phylotypes (MLST), pathovars, hosts, and clinical manifestations via sequence analysis of the mutS-rpoS region. Using a sample collection scheme, addressing epidemiological issues, we intend to establish a collection of 500 strains in both countries. Bioinformatic studies will identify functional single nucleotide polymorphisms. The influence of different mutS-rpoS genomic regions on the transcriptome will be studied by microarray and Real-time PCR analyses using different cell lines/in vivo models and representatives of each mutS-rpoS group and knock-outs of single genes/entire mutS-rpoS genomic regions.
Project 2: Single Nucleotide Polymorphisms (SNPs) of the Toll-Like Receptor (TLR) Signaling System and Susceptibility to Tuberculosis: Functional Epidemiologic Analysis
State of the art: The rapid initiation of an immune response initiated by signal transduction events of the toll-like receptor (TLR) system activating either NF-kB or type-1 interferons is crucial for successful fighting of pathogens and eliminating disease. Extracellular TLRs recognize bacterial cell wall compounds, while intracellular ones, and the rig-helicases sense microbial nucleic acids. Nod-like receptors (NLRs) sense to muropeptides, breakdown products of all bacterial cell walls. Genetic variations of these systems exist and have impact on clinical medicine.
Previous work: We have analyzed genetic variations of the TLR system and found associations with susceptibility and course of diseases. A TLR2 SNP (Arg753Gln) associated with chronic inflammatory disease is completely absent in Africans, and according to first results also very rare in India. The world wide distribution of frequent TLR4 SNPs also differs greatly and may relate to selective pressure and migration patterns of humans. For the TIRAP/Mal Ser180Leu SNP shown to be involved in TB susceptibility, a unique world-wide distribution pattern was found by us. SNPs in TLR1 are important for susceptibility to and clinical course of leprosy, which we showed for a Turkish population, and recently also for Bangladesh involving 1,300 patients and controls.
Working hypothesis and work plan: Our previous work showed that genetic variations in the TLR signalling system of the host are of importance for infectious diseases susceptibility. We hypothesize that genetic variations within these innate immune receptors contribute to epidemiology of tuberculosis in India, and may differ from Europe due to selective pressure. We will study the genetic variation of the TLR system in India and compare it to the distribution in European cohorts. These studies will be flanked by functional molecular analyses aimed at elucidating the consequences of the genetic variations for the host pathogen interaction.
Abilities and requirements: Within the GRK1673 network a large number of genotyping assays have to be established and applied. Furthermore the results have to be evaluated by statistic and bioinformatics methods. Both projects will be performed in close interaction with the University of Hyderabad with regular teleconferences and visits. Applicants should have a completed education in the Natural Sciences, Medicine or Veterinary Medicine with a strong background in Molecular Biology. Experience with PCR-based and other Genotyping methods is needed for both projects. The applicant should be fluent in English and willing to work with and train local and international graduate students. Part of this training will include holding seminars and workshops for graduate students as part of the teaching program of the GRK1673. Experience and knowledge in management and project coordination are helpful as this project will interact with a large number of sub-projects of this graduate school.
Requirements specific to each project:
Project 1:
· The applicant must have good knowledge of bioinformatics software (freeware and/or commercial) for analysing sequence based data (e.g. phylogeny, whole genome sequence annotation and comparison, functional prediction).
· Experience with Next Generation Sequencing methods/data would also be helpful.
· Experience with bacterial manipulation techniques and animal infection experiments is desired.
Project 2:
· The applicant should have experience with the establishment of genotyping protocols.
· Experience with the implementation of sequencing software and net-based data bases for the storage and analysis of data collected is required.
· To this end a large body of clinical data has to be compiled and evaluated, and understanding of medical terminology would be helpful.
To apply for the positions, please send in your complete application to the following addresses at the latest by 01.09.2010
Project 1
Dr. Christa Ewers/Prof. Dr. Lothar H. Wieler
Institute of Microbiology and Epizootics
Freie University Berlin
Philippstr. 13
10115 Berlin
Tel: +49 (030) 2093 6153
Fax: +49 (030) 2093 6067
Project 2
Prof. Dr. Ralf R. Schumann
Institute of Microbiology and Hygiene
Charité – Universitätsmedizin
Dorotheenstr. 96
10117 Berlin
Tel: + 49 (030) 450524141
Fax: +49 (030) 450524941
Email: ralf.schumann@charite.de
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