Cloning and characterization of 10 human blood-brain-barrier transporters
Identification of plasma membrane import routes of Tau, FUS and alpha-synuclein di...
| Grant number: | 17/01986-8 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Start date: | May 01, 2017 |
| End date: | July 31, 2021 |
| Field of knowledge: | Biological Sciences - Biology |
| Agreement: | Coordination of Improvement of Higher Education Personnel (CAPES) |
| Principal Investigator: | Elizabeth Bilsland |
| Grantee: | Ludimila Dias Almeida |
| 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 |
| Associated scholarship(s): | 18/09194-6 - Identification of plasma membrane import routes of Tau, FUS and alpha-synuclein disaggregating compounds using yeast based high-content screening, BE.EP.DR |
Abstract Drugs need to reach their targets (present on the surface or inside the cells) in order to function. Traditionally the pharmaceutical industry has designed new compounds assuming that they would enter the cell by passive diffusion through the plasma membrane, however, there is a growing body of evidence indicating that passive diffusion entry is the exception rather than the rule. Studies indicate that the entry occurs preferentially by the action of carrier proteins in a facilitated transport process. The passage through the blood-brain barrier in particular presents one of the greatest challenges in the development of drugs directed to the central nervous system, as this tissue separates the blood circulation from the interstitial space of the brain, aiming at protection against toxic substances and invading organisms. The knowledge of the specificity of the transporters found in the barrier cells is very important in the correct targeting of drugs in nerve cells. Saccharomyces cerevisiae yeast is a model organism that has been used in chemogenomics for the understanding of the mechanisms of action and transport of drugs. The study of the specificity of yeast transporters is of great importance for the design of drugs, due to the existence of human orthologs of these proteins. In this context, the project aims to define the substrate specificity of 121 non-essential yeast transporters. We aimed to utilize a newly constructed library of lineages containing deletions in pairs from nonessential yeast transporters for the determination of the specificity of these proteins to a library of compounds and commercial drugs of the central nervous system. We will also study the specificity of human orthologous transporters, combining laboratory experiments and bioinformatics. The project will provide a basis for the design of new drugs for both pathogenic yeasts and human targets. (AU) | |
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