EMU granted in FAPESP process 13/ 08028-1 - Mayana Zatz: BD FACSymphony" Flow Cytometer

Abstract

The Human Genome Research Center (HGRC-CEPID I) was initiated in 2000 with the main goal of increasing our basic knowledge and diagnosis of prevalent genetic diseases in the Brazilian population. The HGRC concentrated largely on Mendelian disorders, mainly neuromuscular, craniofacial, and mental disability. The scope was expanded in 2005 by incorporating stem-cell research, both as a tool to understand gene expression and differentiation in genetic disorders and to evaluate its potential in disease therapy. Our research has allowed us to address questions on the genetic regulation of particular complex disorders such as autism and various neurodegenerative diseases. However, the unanticipated complexity of the transcriptional mechanisms regulating gene expression in humans that emerged from the Human Genome Project, and the modest advances in improving the effectiveness of genetic health care have opened new fields of investigation. In this CEPID 11 application, we have expanded the scientific breadth to include ageing and degeneration and how factors such as genome instability contribute to the aging process; the role of imprinting mechanisms on disease manifestation; which factors determine differences in the rate of brain degeneration between individuals, which constitutes a rapidly increasing health care burdon as the average life-span of the world population rises; what determines phenotypic variability between individuals carrying the same mutation. To address these questions we will use up to date approaches, particularly the use of second generation sequencing and sophisticated cell sorting, incorporate a much broader base of scientific expertise, optimize inter-group synergy as well as national and international research collaboration. The plan also contributes to translational medicine mainly in the application of stem-cells in preclinical studies and therapeutic trials for particular genetic disorders.The great number of patients with different genetic disorders that have been ascertained and registered in our center, the largest one in Latin America, and the ethnic variability of the Brazilian population provides an extremely rich foundation for the proposed studies. We are positive that the knowledge gained from CEPID 11 will have an important impact on genetic health care in Brazil. However, such an ambitious and integrated program can only be expedited by the flexibility and long term security offered by CEPID funding. (AU)