Modeling and analysis of NEKs interaction networks, including potential inhibitors

• Grant number: 12/05092-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: July 01, 2012
• End date: September 30, 2012
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Jörg Kobarg
• Grantee: Gabriela Vaz Meirelles
• Supervisor: Avi Ma’ayan
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Institution abroad: Mount Sinai School of Medicine (MSSM), United States
• Associated to the scholarship: 10/17842-6 - SMOLBNet 2.0: Sistems biology applied to the study of interaction networks of the kinases Nek1,4,6-9 and 11 and the development of novel inhibitors, BP.PD

Abstract

Kinases are regulatory proteins involved in virtually all functional aspects of cells, particularly in signaling pathways, and those acting in cell cycle regulation are considered today the most promising anti-cancer therapeutic targets. Mammals have an extended family of 11 Neks (NIMA-related kinases) structurally homologous to the NIMA mitotic regulator essential in Aspergillus nidulans, which have been described as over-expressed in tumors or as targets for mutations in cancer. This project focuses on the development of in silico models for the analysis of interaction networks of Neks and identification of inhibitors with potential for preclinical testing and clinical trials, which can be used in novel anti-cancer therapeutic strategies in the context of Systems Biology. We intend to apply computational modeling to analyze the Neks interaction network, and to validate the perturbation of this network as a possible treatment for many different types of cancer. In addition, there will be a training in graph theory, machine learning techniques, dynamic modeling and development of programs targeted to the area of Systems Biology, to enable the implementation of a bioinformatics platform for high-throughput analysis, to enable the validation of therapeutic targets and drug design, in our laboratory in Brazil. (AU)