Engineering gene circuits in Saccharomyces cerevisiae

• Grant number: 19/15689-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2019
• End date: March 31, 2020
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Elizabeth Bilsland
• Grantee: Ali Salim Faraj Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 15/03553-6 - Engineering yeast cells for drug discovery, AP.JP

Abstract

Drugs directed to the central nervous system frequently fail in clinical trials because of their poor transport into the brain. This is due to the inefficient import of drugs through the blood-brain barrier. In this project, we aim to use the yeast Saccharomyces cerevisiae as host for expressing human blood-brain barrier transmembrane proteins. We will construct yeast strains where the native ergosterol synthesis pathway is engineered to promote the alternate induction of the yeast pathway versus a synthetic human sterol synthesis pathway. We will design a set of combinatorial synthetic promoters to control the cholesterol synthesis pathways, in order to evaluate the optimum dosage of each gene to promote optimum plasma membrane incorporation of human transporters. Yeast strains with human mimetic plasma membrane will be employed as hosts for the heterologous expression of several human transmembrane proteins for functional studies, which can assist the rational design of drugs targeting the central nervous system. (AU)