A new look at operational tolerance using systems biology strategies

• Grant number: 13/07588-3
• Support Opportunities: Scholarships abroad - Research
• Start date: July 15, 2013
• End date: July 14, 2014
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Verônica Porto Carreiro de Vasconcellos Coelho
• Grantee: Verônica Porto Carreiro de Vasconcellos Coelho
• Host Investigator: Maria Puerto Hernandez-Fuentes
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: University of London, England

Abstract

Operational tolerance is a term used for the immunological phenomenon in human transplantation, in which transplanted individuals maintain normal graft function, after the complete withdrawal of immunosuppressive drugs. This phenomenon has been the focus of intense investigation both in Europe and in the USA for several decades, more recently by two major international consortia, the Immune Tolerance Network (USA) and Indices of Tolerance (Europe). For the last six years, we have been conducting the Brazilian Multicenter Study on Operational Tolerance, in renal transplantation, and our data have contributed to understanding the potentially underlying immunologic mechanisms. Despite the worldwide effort, there is still a need for a more integrated analysis of the vast amount on operational tolerance of data and for determining reliable biomarkers, which may help to identify patients under immunosuppressant, who could eventually evolve to OT and benefit from drug reduction. We here propose to integrate current datasets from The Brazilian Multicenter Study on Operational Tolerance, using Systems Biology strategies, aiming to develop a novel and more systemic understanding of this complex biological phenomenon, and to propose combination of potential biomarkers. Systems biology has emerged as a novel interdisciplinary thinking that integrates biology, computational science, physics, mathematics and several other fields of knowledge, and may be used to broaden our horizon of complex biological processes, such as operational tolerance. To this end, we will count on the valuable collaboration of two outstanding research groups on operational tolerance and Systems Biology, at King´s College London and at Massachusetts Institute of Technology, respectively. (AU)