Human thymus functional genomics: detection of communities in gene coexpression networks and study of transcriptional control

• Grant number: 16/18280-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2016
• End date: April 25, 2019
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Magda Maria Sales Carneiro-Sampaio
• Grantee: Lucila Habib Bourguignon Oliveira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 14/50489-9 - Human thymus: development and diseases, AP.TEM

Abstract

The human thymus is a primary lymphoid organ that plays a critical and unique role in the development and maturation of T lymphocytes. It is a dynamic organ that undergoes rapid changes in time and exogenous and enter a process of involution , altering the immune response dependent on these cells.This project will conduct an investigation into the functional genomics of human thymus (surgical explants obtained in cardiac surgery) in the first 30 months of life employing methods of gene expression in a large scale - using microarrays and computational approaches to identify genes communities (modularity analysis of transcriptional repertoires) in gene coexpression networks (GCN). This study includes a number of healthy individuals, to study the variance of transcriptional profiles in different age groups (in the range of 0 - 30 months). As possibly changes in transcriptional profiles and gene coexpression networks over time involve epigenetic mechanisms, we will also performed a global analysis of microRNA expression. The results will be validated by immunohistochemistry in thymic tissue samples. Importantly, the community detection methodology in complex networks is asserting itself as an essential tool in genomic studies, with relevant applications in network medicine. The characterization of the thymus in healthy infants will provide a network-based approach and the understanding of molecular mechanisms that control this organ, allowing comparative studies with associated diseases, for example chromosomal abnormalities. (AU)