КП-06-Рила-1 In vitro models to study the role of N6-methyladenosine in human pulmonary inflammation

Цел на проекта: This pilot project will investigate the putative role of internal RNA modification, specifically N6-methyladenosine, during the pre-fibrotic inflammatory stage of fibrotic interstitial lung disease. Specifically, we will study whether METTL3/14-mediated RNA methylation: i) exacerbates the innate immune response to inflammatory injury in the alveolar compartment; and ii) accelerates the emergence of a senescence-associated secretory phenotype (SASP) with paracrine activity, a hallmark of fILD. In order to achieve this, we will establish an advanced in vitro model of human alveolar inflammation using the alveolus-on-chip (AoC) and a model of bronchial epithelium inflammation using air-liquid-interface (ALI) differentiated normal human bronchial epithelial cells (NHBEs).
Two research teams will combine their expertise to achieve these goals. The partner from the Stephan Angeloff Institute of Microbiology (SAIM), led by Assist. Prof Milena Leseva, has expertise in immunology, epigenetics and molecular cell biology. The partner from Institut Pasteur-Lille, led by Prof. Alexandre Grassart, is specialized in using advanced tissue bioengineering and microfluidics, specifically the gut-on-chip and lung-on-chip platforms, to study the mechano-biology of host-pathogen interactions.