Objetivo Precise regulation of gene expression is achieved through the coordinated action of genomic cis-regulatory modules (CRMs). The identification of CRMs has long been a goal of functional genomics as CRM dysregulation can have devastating consequences for health and development such as autism. For example, mutations in the MeCP2 gene, which encodes protein that binds methylated DNA and regulates gene expression in neurons, results an Autism Spectrum Disorder termed Rett Syndrome. While thought to modulate CRM activity as a repressor, MeCP2’s function remains ambiguous and would benefit from a functional genomics characterization. To identify CRMs I recently developed a novel approach called FIREWACh. Here, I propose to utilize FIREWACh first to identify active CRMs within a homogenous population of neurons, identifying genomic loci of CRMs whose function may be compromised by MeCP2 mutations. I will adapt FIREWACh to allow the quantification of CRM output in a new method I propose to call ROQ-WACh (regulatory output quantification within accessible chromatin) by addition of barcodes to reporter mRNAs. This will allow high-throughput readout of CRM activity globally in vivo and will be broadly applicable to many biological fields. Lastly, I aim to combine the above approaches to quantify the changes in CRM output in response to pathological mutations in MeCP2. This Marie Sklodowska-Curie Action will allow me (the Experienced Researcher, Matthew Murtha) mobility to Spain to join the laboratory of Dr. Manel Esteller (Host Supervisor), renowned epigeneticist and expert in DNA-methylation biology to perform the research. Together the approaches and data generated by this MSCA action will provide key insights into the relationship between methylated DNA, precise control of gene expression, and high-order phenotypes such as cognitive behaviors. Ámbito científico natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepathology Programa(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 Tema(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Convocatoria de propuestas H2020-MSCA-IF-2015 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF-EF-ST - Standard EF Coordinador FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE Aportación neta de la UEn € 158 121,60 Dirección AVENIDA GRAN VIA HOSPITALET 199-203 08908 L'Hospitalet De Llobregat España Ver en el mapa Región Este Cataluña Barcelona Tipo de actividad Research Organisations Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 158 121,60
