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Engineering gene circuits in Saccharomyces cerevisiae

Grant number: 19/14146-3
Support type:Scholarships in Brazil - Master
Effective date (Start): April 01, 2020
Effective date (End): July 31, 2021
Field of knowledge:Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
Principal Investigator:Elizabeth Bilsland
Grantee:Ali Salim Faraj Silva
Home 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)