| Grant number: | 15/03553-6 |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| Start date: | October 01, 2015 |
| End date: | December 31, 2021 |
| Field of knowledge: | Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms |
| Principal Investigator: | Elizabeth Bilsland |
| Grantee: | Elizabeth Bilsland |
| Host Institution: | Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| Associated scholarship(s): | 19/14146-3 - Engineering gene circuits in Saccharomyces cerevisiae,
BP.MS 19/17876-2 - New tools for synthetic biology in Saccharomyces cerevisiae, BP.IC 19/15689-0 - Engineering gene circuits in Saccharomyces cerevisiae, BP.MS + associated scholarships - associated scholarships |
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 though the blood brain barrier. In this project, we aim to use the yeast Saccharomyces cerevisiae as a platform for studying the transport of chemicals into and out of cells. We will construct yeast strains with deletions of pairs of genes expressing of each of the 121 non-essential plasma membrane transporters, and use these in high-throughput screens to identify groups of proteins with overlapping substrate specificities as well as to define chemical groups preferentially using that particular import route. We will construct yeast strains where the native ergosterol synthesis pathway is replaced for a synthetic human cholesterol synthesis pathway. We have promising preliminary results indicating that strains with cholesterol in their plasma membranes have the ability to efficiently incorporate human trans-membrane proteins. Therefore, strains with a humanized plasma membrane can be hosts for the heterologous expression of blood-brain barrier transporters. Thus, they will be used in screening to identify chemical groups preferably imported by each route, facilitating efficient design of drugs directed to the central nervous system. The humanized strains may also be used in the search for inhibitors of cholesterol synthesis, and for large-scale expression of trans-membrane proteins for structural and functional studies. (AU)
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