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Implications of antibody repertoires for microbiome composition and susceptibility to asthma

Description 
Asthma is a major clinical problem worldwide and its prevalence is on the rise. As an example, 1 in 9 Australians have asthma, which accounts for around 2.5 million people. The role of microbiota in modulating susceptibility to asthma, though emerging, is still largely unexplored and the probiotics that could ameliorate the symptoms of this disease are currently not available. In addition, the impact of antibody repertoire on the selection of microbial species is poorly characterized. To shed some light on the above issues, we made use of B cell transgenic mice with the antibody repertoire fixed to a single antigen. We observed that these mice harbour distinct microbial community, which protects them against house dust mite-induced asthma and identified two bacterial genera that strongly associate with this protection. The purpose of this project is to test the probiotic potential of identified bacteria and define the rules behind their selection in vivo, with the particular emphasis on the role of transgenic B cells and monoclonal antibodies in this process. This approach will bridge basic and translational research and may have implications for the design of novel probiotic-based strategies for asthma treatment. Depending on the student’s interests, one out of three projects will be followed: 1) Unravelling the rules governing microbiota selection in B cell transgenic mice This project will involve studying antibody-microbiota interactions and their consequences for the colonization of microbial species in mice. Techniques to be used will include: bacterial cell sorting, flow cytometry, ELISA, DNA isolation, next generation sequencing, bioinformatics analyses, histological examination of samples and manipulation of mice (intravenous injections of cells, intranasal administration of allergens, dissection). 2) Unravelling the cellular mechanisms behind the protection of B cell transgenic mice against asthma This project will involve tracking of uptake and activation of lung cells upon intranasal instillation of fluorescently labelled allergens. Techniques to be used will include: chemical labelling of proteins, flow cytometry and manipulation of mice (intranasal administration of allergens, dissection). 3) Evaluation of the immunomodulatory properties of identified bacterial strains We are currently cultivating bacterial strains associated with the protection against asthma. The aim of this project will be testing the probiotic potential (prophylactic and therapeutic) of cultivated strains in a mouse model of asthma. Techniques to be used will include: bacteriological cultures, flow cytometry, ELISA, histological examination of samples and manipulation of mice (intranasal administration of allergens, dissection). Recommended literature: 1) https://www.ncbi.nlm.nih.gov/pubmed/27066758 2) https://www.ncbi.nlm.nih.gov/pubmed/28971969 3) https://www.ncbi.nlm.nih.gov/pubmed/26362264 4) https://www.ncbi.nlm.nih.gov/pubmed/26595731
Essential criteria: 
Minimum entry requirements can be found here: https://www.monash.edu/admissions/entry-requirements/minimum
Keywords 
asthma, lung, microbiota, bacteria, probiotic, antibodies
School 
Central Clinical School
Available options 
Masters by Research
Honours
BMedSci (Hons)
Time commitment 
Full-time
Physical location 
AMREP
Co-supervisors 
Dr 
Tomasz Wypych

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