We wish to develop a coherent account of the synthesis of polyamines (putrescine, spermidine and spermine) in the mold, Neurospora crassa as a model for this pathway in eucaryotic organisms. Using mutations affecting each step of the pathway, including the key enzyme, ornithine decarboxylase, we will identify with certainty the metabolites which govern the regulation of the path. In addition, mutations of the regulatory elements themselves will be used to dissect the genetic control of the augmentation and inactivation of ornithine decarboxylase. In the course of the metabolic studies, the localization of the sequestered spermidine pool will be refined. With pure ornithine decarboxylase and a polyclonal antibody to it, we shall determine the molecular basis of the augmentation and inactivation of the enzyme. With recombinant DNA techniques, we shall clone the structural gene for ornithine decarboxylase, spe-1, and use it as a probe for the messenger RNA which encodes the enzyme. This will allow us to study the extent to which transcription governs the regulation of ornithine decarboxylase. The results will identify the major elements of regulation in a tractable system. This will aid in clarifying the important, but obscure, relationship of the polyamines to growth and neoplasia in mammalian systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM035120-06
Application #
3287249
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1985-07-01
Project End
1995-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697