Gene edition of the aryl hydrocarbon receptor by the CRISPR-Cas9 vector system RNA guide in melanoma

• Grant number: 17/04789-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2017
• End date: November 30, 2018
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Ana Campa
• Grantee: Daniella Teixeira Garcia
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The aryl hydrocarbon receptor (AHR) has been subject of research for its importance in physiological processes and diseases, such as immunological tolerance and tumor immuno-escape. Exogenous and endogenous compounds are ligands of AHR. Kynurenine (Kyn), one of the metabolites resulting from the degradation of tryptophan (Trp), stands out among the endogenous ligands of AHR. In relation to other molecules from Trp metabolism, the identification of AHR ligands is still poor known. Recognizing new AHR ligands and their specific cellular effects seems to be quite relevant, especially among the wide range of Trp metabolites. Several products originating from the Trp metabolizing pathways affect tumor proliferation and the cross talking of tumor cells with the immune system. Based on the previous knowledge of our research group on Trp metabolites on tumor microenvironment, this project proposes the construction of an AHR knockout in melanoma lines and the subsequent evaluation of AHR importance in the biological effects triggered by Trp metabolites. To this goal, we will use the newest genetic editing tool, CRISPR-Cas9, which is a more modern and more efficient version when compared to other already known methods. (AU)