Objective The BILU syndrome is an autosomal dominant primary immunodeficiency that combines B cells Immunodeficiency, Limb abnormalities and Urogenital malformations. Recently, we discovered the genetic basis of this disorder using whole exome sequencing. The causative mutation affects the protein that is involved in mediating transcriptional responses after activation of nuclear receptors (e.g. sex hormone receptors). Altered signalling via nuclear receptors is likely to impact a wide range of genes implicated in development, homeostasis and metabolism leading to the BILU syndrome. In this proposal, we develop a strategy to characterize the impact of the newly discovered mutation on nuclear receptor signalling. We will use analysis of patients’ primary fibroblasts, induced pluripotent stem (iPS) cells and CRISPR-Cas9 edited cell lines to investigate how the mutation impacts transcriptional responses after hormonal stimulations. This project will give insights in the function of the newly identified protein that is involved in the BILU syndrome and will help to understand its broader role in regulation of gene transcription. Fields of science medical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsmutationnatural scienceschemical sciencesanalytical chemistrymass spectrometrymedical and health sciencesbasic medicinephysiologyhomeostasisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes 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-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Net EU contribution € 183 454,80 Address Trinity lane the old schools CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments 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 Other funding € 0,00
