Project description DEENESFRITPL Calcium regulation of mucin secretion The epithelium in the airways and gastrointestinal tract is covered by a layer of mucus produced by goblet cells, which can modify their secretory properties to adapt to the continuous changes in the epithelium. The most abundant proteins in the mucus layer are mucins; defects in mucin secretion cause mucus abnormalities, epithelial stress and dysfunction that can lead to microbial infections, chronic inflammation and more aggressive pathologies such as cystic fibrosis, asthma and chronic obstructive pulmonary disease. The EU-funded ICaRMuSs project will address how calcium regulates the trafficking, sorting and secretion of mucins, providing new insights into mucus physiology and determining which membrane proteins are important for mucin secretion. Show the project objective Hide the project objective Objective The epithelium in the airways and gastrointestinal track are covered by a mucus layer which protects the epithelium from mechanical and microbial insults. The most abundant proteins in the mucus layer are mucins which are synthesized and secreted by goblet cells. Mucus function is largely dictated by mucin composition and goblet cells can modify their secretory properties to adapt to the continuous changes the epithelium is encountered with. Mucins are heavily glysosylated and packed into secretory vesicles in the Golgi apparatus. A calcium signal triggers the fusion of the secretory vesicles with the plasma membrane releasing mucins to the extracellular space. The role of intragranular calcium remains a mayor gap in our understanding of mucin physiology and how goblet cells precisely control mucus composition remains only a matter of speculation. These are highly relevant questions as defects in mucin secretion cause mucus abnormalities, epithelial stress and dysfunction that can lead to microbial deleterious infections, chronic inflammation and more aggressive pathologies such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease.In this project I will address how calcium regulates the trafficking, sorting and secretion of mucins, filling current gaps in our understanding of mucus physiology. I will genetically engineer mucin-secreting cells with the CRISPR/Cas9 tools to add GFP and RFP to MUC5AC and MUC2 loci and describe granular composition by super resolution microscopy and FACS. I will use a first-in its kind probe to measure intragranular calcium concentration and finally I will purify secretory granules and sequence them with mass spectrometry to determine which membrane proteins are important for mucin secretion. This project will allow me to apply my experience in highly relevant questions in cell biology and it will also enhance my creative and innovative potential through advanced training and international mobility. Fields of science medical and health sciencesclinical medicinepneumologyasthmanatural scienceschemical sciencesinorganic chemistryalkaline earth metalsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator FUNDACIO CENTRE DE REGULACIO GENOMICA Net EU contribution € 172 932,48 Address CARRER DOCTOR AIGUADER 88 08003 Barcelona Spain See on map Region Este Cataluña Barcelona Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 172 932,48
