Functional and molecular implication of human Nek10 in centrosome function

• Grant number: 16/07815-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: July 01, 2016
• End date: June 30, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Edmarcia Elisa de Souza
• Supervisor: Michael Lampson
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Pennsylvania, United States
• Associated to the scholarship: 14/06873-9 - Study of the molecular and functional role of Nek7 and Nek10 in the regulation of cell division associated with cancer, BP.PD

Abstract

Human Nek10 is a not completely characterized Nek family member that is implicated as a player in different types of cancer. We previously showed that Nek10 is localized to centrosome and provided the first evidences of its roles in regulating mitotic centrosome and spindle function and its potential connection with genomic instability. However, exact Nek10 roles in regulating mitotic-centrosome function and their implication in cancer are still far from being fully elucidated. In this project, we propose to investigate Nek10 roles in regulating critical mechanisms underlying mitotic-centrosome function whose deregulation are most frequently described how abnormalities that contribute genomic instability and cancer. To this end, first, we will use time-lapse live imaging combined with immunofluorescence microscopy for identification and monitoring in vivo of phenotypic alterations arising from untransformed or chromosomally-instable RNAi Nek10-deficiency cells. Secondly, we will specifically focus on the localization of Nek10 to the centrosome with focus to its roles in maintaining the genomic integrity. In this regard, we will use complementary approaches of rapamycin-induced dimerization and optogenetics to investigate effects of centrosomally-localized Nek10 and/or its activity during the normal or perturbed mitotic progression as well as upon spindle and/or pole perturbation by time-lapse live imaging combined with immunofluorescence microscopy. These approaches will provide important insights into centrosomal Nek10 functions as well as functional and molecular pathway of Nek10 implication in cancer. (AU)