Programmed cell death plays a central role in development and in multiple diseases, notably cancer and neurodegenerative disorders. -The long-term objective of this proposed research is to further understand the mechanisms of programmed cell death and its role in development. The model being used is the ovary of the fruitfly, Drosophila melanogaster, a system with unique advantages for the study of cell death. Programmed cell death of ovarian nurse cells is essential for proper oocyte development. Nurse cells possess distinct traits which make them an ideal model for analyzing cell death in vivo. These cells are abundant, die synchronously in clusters, and are large, making them amenable to subcellular analyses. Furthermore, disruption of nurse cell death results in sterility, a phenotype that permits straightforward genetic analysis. This proposal addresses multiple aspects of the nurse cell death pathway.
The specific aims are to 1) further address the requirement for caspases in this pathway by the expression of constitutively active Drosophila caspase- 1 (Dcp- 1) in the germline, the characterization of new alleles of dcp-1, and the characterization of the caspase Drice; 2) isolate additional genes involved in nurse cell death by histological examination of mutants previously shown to have defects in oogenesis; and 3) test the role of individual caspase targets during cell death in vivo by the expression of cleavage-defective molecules. These experiments should yield an understanding of the molecules that are critical for nurse cell death, from the initial signal to the final proteolyzed targets. This knowledge is likely to have implications for other cell death pathways in Drosophila and other organisms.
| Santoso, Clarissa S; Meehan, Tracy L; Peterson, Jeanne S et al. (2018) The ABC Transporter Eato Promotes Cell Clearance in the Drosophila melanogaster Ovary. G3 (Bethesda) 8:833-843 |
| Timmons, Allison K; Mondragon, Albert A; Meehan, Tracy L et al. (2017) Control of non-apoptotic nurse cell death by engulfment genes in Drosophila. Fly (Austin) 11:104-111 |
| Serizier, Sandy B; McCall, Kimberly (2017) Scrambled Eggs: Apoptotic Cell Clearance by Non-Professional Phagocytes in the Drosophila Ovary. Front Immunol 8:1642 |
| Timmons, Allison K; Mondragon, Albert A; Schenkel, Claire E et al. (2016) Phagocytosis genes nonautonomously promote developmental cell death in the Drosophila ovary. Proc Natl Acad Sci U S A 113:E1246-55 |
| Klionsky, Daniel J (see original citation for additional authors) (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12:1-222 |
| Meehan, Tracy L; Serizier, Sandy B; Kleinsorge, Sarah E et al. (2016) Analysis of Phagocytosis in the Drosophila Ovary. Methods Mol Biol 1457:79-95 |
| Meehan, Tracy L; Joudi, Tony F; Timmons, Allison K et al. (2016) Components of the Engulfment Machinery Have Distinct Roles in Corpse Processing. PLoS One 11:e0158217 |
| Meehan, Tracy L; Yalonetskaya, Alla; Joudi, Tony F et al. (2015) Detection of Cell Death and Phagocytosis in the Drosophila Ovary. Methods Mol Biol 1328:191-206 |
| Peterson, Jeanne S; Timmons, Allison K; Mondragon, Albert A et al. (2015) The End of the Beginning: Cell Death in the Germline. Curr Top Dev Biol 114:93-119 |
| Perkins, Lizabeth A; Holderbaum, Laura; Tao, Rong et al. (2015) The Transgenic RNAi Project at Harvard Medical School: Resources and Validation. Genetics 201:843-52 |
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