In TR&D 1, we develop approaches to make complex changes to cells, and we generate biosensors to report on the effects of some of these changes. In the first aim, we establish strategies to rapidly and combinatorially up- or down-regulate a set of genes in a common pathway in order to improve the expression of a desired protein, and optimize these approaches using a vaccine protein that is commercially made in yeast. In the second aim, we devise new selections for use in chemostats and turbidostats to identify the effects of small changes in proteins, in promoters and in untranslated regions of mRNAs. Further, we modify the turbidostat platform to enable ramped selections, allowing feedback on temperature or drug concentration to optimize selections. In the third aim, we design new proteins that bind to a protein-protein interface and disrupt an interaction. These inhibitory proteins will allow us to assess the roles of individual members of large protein families that are difficult to analyze. Finally, in the fourth aim, we generate new biosensors to detect the levels of a small molecule and of a protein produced in yeast.

Agency
National Institute of Health (NIH)
Type
Biotechnology Resource Grants (P41)
Project #
2P41GM103533-21
Application #
9208071
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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