The goal of this project is to develop the use of peptide aptomers that interfere with protein function in vivo. Peptide aptomers are short peptides (fused to a platform molecule, E. coli thioredoxin) that interact specifically with a target protein. Aptomers that disrupt specific protein/ protein interactions can be selected using the yeast two-hybrid system and then expressed in Drosophila in spatially and temporally controlled patterns. Previous results from this group have shown that peptide aptomers can be used to specifically target and inhibit cell cycle regulators in vivo, and using two hybrid approaches they have identified a network of protein interactors, that includes known and potential cell cycle regulators. The proposal has four Specific Aims. 1) To improve the technology for the isolation and subcloning of aptomers. 2) To test the aptomer approach by expressing aptomers that disrupt interactions between Cdk2, Cyclin E and Dacapo in the Drosophila eye. 3) To partially characterize novel proteins from a network of interacting proteins to identify a core group that are likely to regulate the cell cycle in the developing eye. 4) To use peptide aptomers to analyze the function of this core group of proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM062403-03
Application #
6628943
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Zatz, Marion M
Project Start
2001-02-01
Project End
2005-01-31
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
3
Fiscal Year
2003
Total Cost
$273,702
Indirect Cost
Name
Wayne State University
Department
Genetics
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Stanyon, Clement A; Liu, Guozhen; Mangiola, Bernardo A et al. (2004) A Drosophila protein-interaction map centered on cell-cycle regulators. Genome Biol 5:R96