While all cells ultimately die, very little is known about the molecular mechanisms which bring about this developmental phenomenon. One very attractive model system for study, is the intersegmental muscles (ISM) of the moth Manduca sexta, which die during the 36 hours following adult emergence. The commitment of the ISM to degenerate involves the activation of a new set of cell death genes, five of which have been cloned in my lab. The experiments outlined in this proposal will provide insight into the identity and function of these genes in both insects and vertebrates. A range of molecular approaches will be used to isolate, sequenced and express cell death genes. Additionally, culture cells and insect muscle fibers will be injected or transfected with one of the following molecules generated from our clones: anti-sense transcripts, sense transcripts, antibodies, purified expressed proteins or recombinants made with a reporter gene fused to putative cell-death gene promotors. These experiments should greatly increase our understanding of the molecules which are used by cells to die during development and aging. I am currently an assistant professor of Zoology, with a background in physiology, membrane biophysics and recently, molecular biology. My teaching and administrative commitments are quite demanding, which limits my ability to both learn new techniques and visit other labs for training. The time made available by an RCDA will dramatically increase my ability to exploit this powerful cell death model system. It is clear that examination of such model systems will provide basic insight into the molecular mechanisms which mediate senescence and death in animal cells.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Modified Research Career Development Award (K04)
Project #
5K04AG000492-02
Application #
3070606
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1990-09-01
Project End
1995-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Massachusetts Amherst
Department
Type
Schools of Arts and Sciences
DUNS #
153223151
City
Amherst
State
MA
Country
United States
Zip Code
01003
Sun, D; Sathyanarayana, U G; Johnston, S A et al. (1996) A member of the phylogenetically conserved CAD family of transcriptional regulators is dramatically up-regulated during the programmed cell death of skeletal muscle in the tobacco hawkmoth Manduca sexta. Dev Biol 173:499-509
Fahrbach, S E; Schwartz, L M (1994) Localization of immunoreactive ubiquitin in the nervous system of the Manduca sexta moth. J Comp Neurol 343:464-82
Osborne, B A; Smith, S W; Liu, Z G et al. (1994) Identification of genes induced during apoptosis in T lymphocytes. Immunol Rev 142:301-20
Schwartz, L M; Smith, S W; Jones, M E et al. (1993) Do all programmed cell deaths occur via apoptosis? Proc Natl Acad Sci U S A 90:980-4
Schwartz, L M; Jones, M E; Kosz, L et al. (1993) Selective repression of actin and myosin heavy chain expression during the programmed death of insect skeletal muscle. Dev Biol 158:448-55
Schwartz, L M; Osborne, B A (1993) Programmed cell death, apoptosis and killer genes. Immunol Today 14:582-90
Schwartz, L M (1992) Insect muscle as a model for programmed cell death. J Neurobiol 23:1312-26
Schwartz, L M (1991) The role of cell death genes during development. Bioessays 13:389-95