Our goal is to understand the molecular pathway leading to programmed cell death in C. elegans. Naturally occurring or programmed cell deaths play an important role in animal development and homeostasis. Such deaths, which remove cells that are not needed or are potentially dangerous, are observed in a wide variety of tissues in both vertebrates and invertebrates. Proper control of programmed cell death is very important: breakdown in the regulation of this process appears to be associated with several types of cancer, autoimmunity and possibly neurodegenerative diseases. Recent studies by us and others have established that the genetic pathway for programmed cell death found in C. elegans is conserved and also functions in mammals. Thus, knowledge gained about nematode programmed cell death will further understanding of this phenomenon in humans. We have recently undertaken an in-depth study of programmed cell death in the germ line of C. elegans. The germ line tissue offers a number of advantages over the C. elegans soma, including a more vertebrate-like regulation of proliferation and the possibility of isolating significant amounts of dying cells for biochemical analysis. Our preliminary studies indicate that programmed cell death is a major - albeit so far mostly ignored - cell fate in the germ line and that many, but not all, of the genes involved in programmed cell death in the soma also function in the germ line. To further our understanding of the molecular mechanisms that lead to programmed cell death in the germ line, we will: 1) Determine how known genes affect the germ line deaths. 2) Identify and genetically characterize new genes that affect programmed cell death in the germ line. 3) Clone and molecularly characterize genes affecting germ line programmed cell death. 4) Use the C. elegans germ line for pharmacological and biochemical studies of programmed cell death. 5) Determine how environmental conditions modulate cell death in the C. elegans germ line. These studies will increase our knowledge of the molecular mechanism of programmed cell death in C. elegans. The similarities between the cell death pathway in nematodes and mammals suggest that our studies will also identify candidate genes involved in the regulation and execution of programmed cell death in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM052540-04
Application #
2701680
Study Section
Special Emphasis Panel (ZRG2-HED-2 (01))
Project Start
1995-05-01
Project End
2000-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
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Chung, S; Gumienny, T L; Hengartner, M O et al. (2000) A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C. elegans. Nat Cell Biol 2:931-7
Hengartner, M O (1999) Programmed cell death in the nematode C. elegans. Recent Prog Horm Res 54:213-22;discussion 222-4
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