Prevention/therapy of allergic sensitization and allergy development in gnotobiotic mouse models

(Prevence/terapie alergické senzibilizace a vývoje alergického zánětu v gnotobiotickém myším modelu)

Allergies are widespread pathological immune reactions which are initiated by generally harmless food/airborne antigens. Their global prevalence have been increasing since the 1960s, especially in industrialized countries, suggesting environmental factors play a key role in the susceptibility and etiology of this disorder. The development of allergy is a two-step process: i) allergic sensitization and ii) the effector phase. The humoral and cellular immune responses are clearly biased toward a type 2-related phenotype, characterized by the production of specific IgE antibodies and cytokines, such as IL-4, IL-5, IL-13, or IL-10. In the effector phase, allergen-induced crosslinking of IgE bound to mast cells or basophils leads to release of allergic mediators resulting in the rapid appearance of symptoms, such as sneezing, itching, swelling or diarrhea in case of food allergies. The hygiene hypothesis postulates that behind the increased susceptibility to allergic diseases is the lack of exposure to microbial stimuli or altered microbial stimulation, which leads to aberrant immune system maturation. Along these lines, dysbiotic microbiota leading to allergy development or associated with allergic diseases has been reported to have decreased or lack of certain groups of commensal bacteria including lactobacilli and bifidobacteria.

Within the framework of the Ph.D. you will master the handling with germ-free and conventional mice and work with mouse models of food and airway allergies. Specifically, you will investigate the impact of selected probiotic and commensal bacteria (such as lactobacilli, bifidobacteria or non-pathogenic E. coli) and defined isolated bacterial components on the development of naive immune system and allergic sensitization/inflammation in mouse model.

During your PhD. study you will use classical and molecular-biological methods for bacterial detection and cultivation. You will master different methods such as ELISA, Western-blot, PCR and real-time PCR, flow cytometry, in vitro cell and cell line cultivation, histology and immunohistochemistry.

Integrative Physiology of Gnotobionts research group is funded by grants from Czech Grant Agency and EMBO Installation grant.

Location Young and dynamic team of Martin Schwarzer’s group at Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, Doly 183, Nový Hrádek, 54922 (Doctoral studies of Immunology at Charles University in Prague)

Deadline for applications 31. 3. 2020