Identification of genetic signatures of DNA damage response pathways associated with competences of specific cell populations in glioma

• Grant number: 22/15434-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2023
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Valeria Valente
• Grantee: Mateus Priolo Grejo
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Tumors in general are composed of cell populations with distinct molecular characteristics. Theimplications of this heterogeneity are profound, where within a tumor there are multiplesubclones of cells with unique genetic and transcriptional profiles, in which specific clones maybe responsible for tumor recurrence after treatment (QAZI et al., 2017). The molecular study oftumor subclones was initiated with the advent of single cell sequencing technology, in 2009(TANG et al., 2009), since then, single cell analysis approaches and tools have been growingquickly, allowing the segregation of cell populations with specific characteristics and enablingthe search for biomarkers for targeted sensitization of subpopulations cells. Said that, this projectaims to explore single cell sequencing data, along with tumor tissue bulk data, in order tocontribute to a better understanding of genetic profiles related to brain tumors progression andrecurrence, besides the discovery of new potential biomarkers of the disease. The identifiedhallmarks considered as most relevant will be explored in-vitro in glioma cell lines that are goingto be genetically modified for further functional characterization, verifying competencesacquired by the cells, regarding proliferation rates, resistance to genotoxic drugs and capabilityto repair induced DNA damages. Through this, we expect to contribute to a better understandingof the state of genetic heterogeneity of gliomas and to identify and validate alterations in DNArepair genes that may serve as markers for the sensitization of specific cells in these tumors.