Ruprecht-Karls-Universität Heidelberg
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Dalpke0218 - Scientist (f/m) / PhD position
Project no:
Dalpke0218

Project leader:

Project supervisor:
Dalpke, Alexander
Application deadline:
19. Aug 2018
Start of PhD project:
1. Oct 2018

Project description:

Title:
Influence of the airway microbiome on immune responses and Pseudomonas aeruginosa infection in Cystic Fibrosis
Summary:
Studies deciphering the composition of the airways’ microbiota in Cystic Fibrosis have found a correlation between microbiome, lung function and inflammation. Anaerobic commensal bacteria, usually found in the oral cavity, contribute to the polymicrobial infection in CF patients' airways. However, the impact of commensal bacteria on immune responses as well as specific infections remains unclear and controversial.
Based on own preliminary work we hypothesize that commensal bacteria including Neisseria, Veillonella, Prevotella and Streptococcus reduce pro-inflammatory responses and exert protective effects against a subsequent infection with Pseudomonas aeruginosa.
The immunostimulatory potential of commensal bacterial strains isolated from CF patients will be evaluated. The choice of bacteria is made based on studies analyzing the microbiome that were done in the applicant’s laboratory previously. Furthermore the relation between commensal microbiota, inflammatory biomarkers and infection with Pseudomonas aeruginosa will be studied in a running clinical cohort using a combination of next generation sequencing and immunological methods. Candidate commensals will be studied in a preclinical Cystic Fibrosis mouse infection model for protective effects on P. aeruginosa infection and host inflammation.
References:
1. Boutin S, Dalpke AH (2017): Acquisition and adaptation of the airway microbiota in the early life of cystic fibrosis patients. Mol Cell Pediatr 4(1): 1-9

2. Boutin S, Graeber SY, Stahl M, Dittrich AS, Mall MA, Dalpke AH (2017): Chronic but not intermittent infection with Pseudomonas aeruginosa is associated with global changes of the lung microbiome in cystic fibrosis. Eur Respir J ;50:1701086. doi:10.1183/13993003.01086-2017

3. Boutin S, Depner M, Stahl M, Graeber SY, Dittrich S, Legatski A, Von Mutius E, Mall M, Dalpke A (2017): Comparison of oropharyngeal microbiota from children with asthma and cystic fibrosis. Mediators of Inflammation, in press

4. Gehrig S, Duer J, Weitnauer M, Wagner CJ, Graeber SY, Schatterny J, Hirtz S, Belaaouaj A, Dalpke AH, Schultz C and Mall MA (2014): Lack of neutrophil elastase reduces inflammation, mucus hypersecretion and emphysema, but not mucus obstruction, in mice with CF-like lung disease. AJRCCM 189(9):1082-92

5. Boutin S, Graeber SY, Weitnauer M, Panitz J, Stahl M, Clausznitzer D, Kaderali L, Einarsson G, Tunney MM, Elborn JS, Mall MA and Dalpke AH (2015): Comparison of microbiomes from different niches of upper and lower airways in children and adolescents with cystic fibrosis. PLOS One 10(1):e0116029
Methods that will be used:
in vitro and in vivo infection, cultivation of primary epithelial and immune cells, cytokine measurement, bacterial mutagenesis, next gen sequencing, microbiome analysis, conventional microbiology
Cooperation partners:
PD Dr. Olaf Sommerburg
Personal qualifications:
background in microbiology and immunology, sense of ecology, statistics and bioinformatics to run microbiome studies, self-reliance, willingness to work in a close cooperation
Keywords:
infection&immunity, host-pathogen interactions, cystic fibrosis, microbiome, microbial ecology