Unraveling the immunological and microbial mechanisms of hay fever protection by multi-omics data integration

• Applicant: Giulia Pagani, Ph.D.
• Subject Area: Clinical Immunology and Allergology ; Pediatric and Adolescent Medicine ; Medical Informatics and Medical Bioinformatics
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 504087764

Living as a child on traditional farms has been associated to a decreased risk of developing asthma, hay fever and atopy. Several population-based studies have disentangled the different aspects of farming and identified contact with livestock, regular consumption of raw milk, and environmental microbial exposure as the most relevant protective effects. Intriguingly, this so called “farm effect” can be broadly divided into three main pillars: type of exposure, time of exposure, and immunology of exposure. From birth, and already during the prenatal age, upon external exposure, the innate immune system is greatly engaged and shaped. This, in turn, captures and translates the signals to cells of the interconnected adaptive immune system. Albeit findings point towards a crucial role played by modulated microbiome in shaping the host susceptibility to develop allergic diseases later in life, much is still unknown about the cross-talk between the microbial communities and the immune responses. Building on the wealth of knowledge already available, I propose here a multi-omics framework aiming at elucidating the mechanisms of microbiome-associated immunity and its role in the protection from hay fever in farm children from age of 6 to 10 years. The project is composed of two parts: 1) an investigation of the mRNA expression in n=240 children from the PASTURE birth cohort in whole blood samples collected at age of 10 years; 2) in the second part I will focus on establishing a framework for integrating clinical data, microbial responses from mattress dust source at age of 6 and 10 years with associated blood samples to assess the association of beneficial microbes with hay fever related gene expression. For this purpose, I will nest a case-control study in a 1:2 ratio, comparing children bearing a diagnosis of hay fever at age of 10 years against children with and without atopic sensitization in equal shares. Univariate analyses along with state of art machine learning approaches will be applied to identify: i) novel biomarkers and signaling pathways, ii) highly correlated gene-microbial signature(s). Altogether these findings are expected to elucidate how microbiome-associated immunity protects against allergic diseases and it modulates its influences over the course of time.

• DFG Programme: Research Grants
• Co-Investigators: Professor Markus Ege, Ph.D.; Professorin Dr. Erika von Mutius