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Exploring and targeting genetic variants affecting the innate immune pattern recognition receptors

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  • Full or part time
    Prof Alexander Weber
  • Application Deadline
    Applications accepted all year round
  • Awaiting Funding Decision/Possible External Funding
    Awaiting Funding Decision/Possible External Funding

Project Description

Topic and project description: The innate immune systems in mammals rely on the recognition of microbes through conserved molecular patterns by so-called pattern recognition receptors (PRRs). While many PRR signaling pathways have been discovered, the function of PRR in human primary cells and how genetic variation affects PRR function and impacts on disease susceptibility and progression in humans remains largely unknown. Additionally, despite the dawning of an age of individualized approaches in medicine, the therapeutic potential for stratified diagnostic and therapeutic approaches based on PRR genetic variants has not been well investigated. Working in cellular model system, primary human immune cells, variant-genotyped healthy volunteers and patient cohorts, our lab seeks to unravel some of the effects of naturally occurring genetic variance affecting PRR signaling pathways in humans and describe their molecular, cellular, immunological and epidemiological impact. So far our work has mainly focused on Toll-like receptors (TLRs) but recent studies also include receptors of the Nod-like receptor (NLR) PRR family. To advance this important research, we seek to attract highly motivated and gifted students.

Institute and team: You would be part of a dynamic research group with a solid track record, and located in an excellent scientific environment, the Department of Immunology (Head: Prof. Dr. Hans-Georg Rammensee) located on the University and University Hospital campus of Tübingen. In our lab you would find a friendly, well-connected and international environment, a firm commitment to good supervision and professional development, and an excellent instrumental setup. International applicants are very welcome and will be supported in participating in German courses (NB: German skills are not a requirement for application as English will generally be used in the work environment).

Funding Notes

Funding: Fully funded 3 years (~1500 EURO/month), stipend holders welcome.

Your profile: an excellent Masters degree in biology or medicine, and research experience in molecular/cellular biology, microbiology/virology, protein biochemistry or immunology. You are highly motivated to work independently and also as part of a team. You have very good written + spoken English.

Your application: The starting date is flexible. The following documents are mandatory - only complete electronic applications will be reviewed on an ongoing basis:
- Cover/motivation letter (max 1 A4)
- CV
- Transcripts/certificate of diploma and bachelor degree
- Support letter from 1 previous supervisor

References

Suggested reading:

1. Wang H, Flannery SM, Dickhöfer S, Huhn S, George J, Kubarenko AV, Lascorz J, Bevier M, Willemsen J, Pichulik T, Schafmayer C, Binder M, Manoury B, Paludan SR, Alarcon-Riquelme M, Bowie AG, Försti A, Weber AN. A coding IRAK2 variant compromises TLR signaling and is associated with colorectal cancer survival. J Biol Chem. 2014 Jun 19. pii: jbc.M113.492934.
2. Colak E, Leslie A, Zausmer K, Khatamzas E, Kubarenko AV, Pichulik T, Klimosch SN, Mayer A, Siggs O, Hector A, Fischer R, Klesser B, Rautanen A, Frank M, Hill AVS, Manoury B, Beutler B, Hartl D, Simmons A, Weber AN. RNA and Imidazoquinolines are sensed by distinct TLR7/8 ectodomain sites resulting in functionally disparate signaling events. J Immunol. 2014 Jun 15;192(12):5963-73.
4. Klimosch SN, Försti A, Eckert J, Knežević J, Bevier M, von Schönfels W, Heits N, Walter J, Hinz S, Lascorz J, Hampe J, Hartl D, Frick JS, Hemminki K, Schafmayer C, Weber AN. Functional TLR5 genetic variants affect human colorectal cancer survival. Cancer Res 2013;73(24):7232-42.
5. Eckert KJ, Kim YJ, Kim JI, Gürtler K, Oh D-Y, Sur S, Lundvall L, Hamann L, van der Ploeg A, Pickkers P, Giamarellos-Bourboulis E, Kubarenko AV, Weber AN, Kabesch M, Kumpf O, An H-J, Lee J-O and Schumann RR. The Crystal Structure of Lipopolysaccharide Binding Protein Reveals the Location of a Frequent Mutation that Impairs Innate Immunity. Immunity 2013; 39(4):647 – 660.
6. Kawai, T. & Akira, S. Toll‐like Receptors and Their Crosstalk with Other Innate Receptors in Infection
and Immunity. Immunity 34, 637‐650 (2011).



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