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Doctoral Researcher Position: The impact of the interaction of the receptors of the Dectin-1 gene cluster in fungal and bacterial infections

The Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute – in cooperation with the Friedrich Schiller University, the University Hospital Jena and the Max Planck Institute for Chemical Ecology are offering an international graduate training programme. The

International Leibniz Research School (ILRS Jena)
 
gives doctoral researchers the possibility to prepare for their PhD exam in an ambitious program providing excellent research conditions. We invite applications for a
 
Doctoral Researcher Position (Ref.No. ILRS_03/2016)
The impact of the interaction of the receptors of the Dectin-1 gene cluster in fungal and bacterial infections
 
The Dectin-1 cluster forms part of the group V C-type lectin-like receptors that have a single CTLD connected to an intracellular signaling domain via a stalk and transmembrane region and were thought to have arisen through gene duplication. Two of these receptors, Dectin-1 and LOX-1, have been identified as pattern recognition receptors (PRRs). Dectin-1 recognizes β-glucans, a carbohydrate present in cell walls of many fungal species, and is required for immunity to several pathogens including species of Candida , Aspergillus and Pneumocystis . Lox-1 has been described to bind to Staphylococcus aureus and E. coli . However, for most of the receptors of this cluster some endogenous ligands have been identified but a comprehensive analysis of their ability to function as PRRs has not been performed. Functions of receptors within the Dectin-1 cluster are predetermined, in that signaling motif(s) present within their intracellular domain dictate how they respond to extracellular stimuli. The activatory receptors Dectin-1, CLEC-2 and CLEC-9A containing ITAM-like and the inhibitory receptors MICL and MAH are containing canonical ITIM motifs. The C-type lectin-like scavenger receptor LOX-1 is containing a DDL motif and CLEC-1 is containing an uncharacterized tyrosine-based motif. Functions of ITAM bearing receptors which often are dependent on the recruitment of SYK can be counteracted by the action of ITIM bearing receptors. In this case upon co-aggregation with activating receptors, associates kinases phosphorylate the ITIM motif, which can inhibit the activation by the recruitment of the inhibitory tyrosin-phosphatases SHP1/2 or SHIP1/2. The receptors of the Dectin-1 cluster are primarily expressed on myeloid cells such as DCs, macrophages and neutrophils orchestrating a variety of cellular functions, including endocytosis, phagocytosis, cytokine production, apoptosis, activation of NFκB and production of reactive oxygen species. For the transcriptional regulation of the receptors of the Dectin-1 cluster as a paralogous gene cluster it is likely that the timing of activation and the order of receptor expression might reflect the genes' positions within their cluster. However, a comprehensive analysis of gene expression pattern of the receptors of the Dectin-1 cluster and their implication of their function in orchestrating immune responses to microbial associated molecular pattern has not been performed so far.
We hypothesized that the interaction of the ITIM or ITAM bearing receptors of the Dectin-1 gene cluster are fine-tuning pathogen-dependent immune responses in particular of Dectin-1 and LOX-1. In addition LOX-1 one might be an important and so far under recognized receptor for the detection of bacterial and maybe also for fungal pathogens.

In the proposed study the following aims will be addressed:
(i) Analysis of the quantitative expression profiles of the receptors of the dectin-1 cluster on human innate immune cells (granulocytes, monocytes, macrophages, NK cells) and pulmonary epithelial cells
(ii) Generation of cells that differentially are expressing receptors of the Dectin-1 cluster by using the CRISPR/Cas-System (Clustered Regularly Interspaced Short Palindromic Repeats) and subsequent functional analysis of the receptor interactions

We expect:
  • a Master’s degree (or equivalent allowing you to pursue a PhD degree) in Natural or Life Sciences. Research at ILRS is centred around “Microbial and Biomolecular Interactions”. Candidates about to earn their degree are welcome to apply.
  • high motivation and interest to join one of the research areas of ILRS
  • creativity and interest in shaping your own thesis project
  • an integrative and cooperative personality with enthusiasm for actively participating in our lively community
  • very good communication skills in English
  • very good skills in transfection of cells are desirable
We offer:
  • a top-level research environment
  • efficient supervision by a team of advisors
  • a comprehensive mentoring programme
  • courses in state-of-the-art technologies and soft skills
  • strong communication and interaction between the involved institutions
  • Jena – City of Science: innovative business activities, successful scientific centres and a vibrant cultural scene around the famous Friedrich Schiller University

The three-year Doctoral Researcher position is available starting from July 2016. Salary will be paid according to TV-L (salary agreement for public service employees). HKI is an equal opportunity employer.

Further information:
Prof. Dr. Hortense Slevogt, PI, hortense.slevogt@med.uni-jena.de
Dr. Christine Vogler, ILRS Coordinator, ilrs@leibniz-hki.de

The application process is handled exclusively online. Please acquaint yourself with the scientific projects offered on our website and thoroughly follow the instructions for the online application process:
 
www.ilrs.de/vacant-projects.html

Deadline for application: Apr 14, 2016.
Successful applicants will be invited to attend a recruitment meeting in Jena (envisaged date: Jun 09-10, 2016).

Contact detail


How to apply:
The application process is handled exclusively online. Please acquaint yourself with the scientific projects offered on our website and thoroughly follow the instructions for the online application process:
www.ilrs.de/vacant-projects.html

Online Application at: https://www.uni-jena.de/jsmc_online_application/
 
Send application to
Dr. Christine Vogler, ILRS Coordinator, ilrs@leibniz-hki.de

Job profile


Working hours
Full-Time
Contract duration
Temporary
Type of job
PhD Project
Work experience
job experience is not required
Region
Germany (Thüringen)
Working place
07745 Jena
Area of expertise
Biology & Life Sciences, Biotechnology