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Poster Full Abstracts - Cell Death
Poster board number is above title. The first author is the presenter
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abnormalities in autophagy and cytoskeletal components. We also looked to see if our target genes interact with the caspase pathway by over-expressing a
caspase inhibitor along with our genes of interest. These studies will illuminate which cell biological processes are affected in our mutants. Through this
screen we have identified potential new regulators of cell death. Ongoing experiments will reveal the exact role of these specific genes and thus expand on
our understanding of cell death mechanisms in the ovary.
302B
Determination of the contributions of caspases and autophagy to cell death in the ovary.
Jeanne S. Peterson, Kim McCall. Dept Biol, Boston Univ,
Boston, MA.
We are investigating the mechanisms controlling two types of cell death that occur in the fly ovary: developmental death of nurse cells, and starvation-
induced death of entire egg chambers at mid-oogenesis. Starvation-induced cell death requires caspases and shows condensation and fragmentation of nurse
cell nuclei, and enlargement of follicle cells during engulfment of nurse cell material. In
dcp-1
mutants there is failure of nurse cell nuclei to condense, and
egg chambers show premature death of follicle cells. Mid-oogenesis cell death is only partially disrupted in autophagy mutants. In developmental cell death,
in late oogenesis, the nurse cells are removed completely when their cytoplasm is dumped into the oocyte and their condensed nuclei are broken down. This
process is partly affected in caspase or autophagy mutants and is indicated by the persistence of nurse cell nuclei in mature egg chambers. Here we present
our findings on the combined inhibition of caspases and autophagy during both mid and late oogenesis.
303C
An EMS genetic screen to identify mutations that modulate loss of Rb phenotypes.
Tianyi Zhang, Zhentao Sheng, Wei Du. Ben May Department for
Cancer Research, University of Chicago, Chicago, IL.
Retinoblastoma protein (Rb) is a tumor suppressor gene that is often inactivated in a wide variety of human cancers. Rb functions to regulate cell
proliferation, differentiation, as well as apoptosis in both flies and mammalian systems. Interestingly, the effects of Rb loss differ in different regions of the
developing eye disc. For example, the Rb mutant cells in the morphogenetic furrow (MF) but not other regions of eye imaginal disc are very sensitive to
apoptosis. These observations suggest that consequences of Rb loss are modified by genes/pathways function in those different regions. To better understand
the in vivo functions of Rb, a genetic screen was carried out to identify mutated genes which have synergistic effects with Rb loss. We used FLP/FRT to
generate mosaic clones in adult eyes, and compared the differences between single and double clones of the Rb mutants and the EMS-induced mutants.
From about 18,000 EMS alleles on chromosome 2L and 3R, 50 mutants were identified with synergistic effects on clone size or differentiation.
304A
Screening for genes regulating mitochondrial dynamics in Drosophila apoptosis.
Eltyeb Abdelwahid
1
, Michael Thomenius
2
, Sally Kornbluth
2
, Kristin
White
1
. 1) Cutaneous Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA, USA; 2) Department of
Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
Aberrant regulation of mitochondrial dynamics is associated with human diseases, including neurological disorders and cancer. Mitochondrial fission is
associated with apoptosis in a wide variety of model systems including Drosophila. The mechanistic connection between mitochondrial dynamics and cell
death in flies remains largely uncharacterized. We have recently shown that the conserved mitofusin (dMFN/MARF) mediates mitochondrial fusion and
promotes Drosophila cell survival. MARF physically interacts with the apoptosis regulator Reaper. We also showed that MARF knockdown causes tissue
loss and significant cell death in Drosophila. Using these findings, we are performing an RNAi screen for genes that modify the MARF RNAi phenotype.
Our screen identified a number of candidates that suppress the MARF RNAi mitochondrial phenotype, and those that suppress MARF RNAi induced tissue
loss independently of the mitochondria, possibly acting downstream of mitochondrial fission. We are currently characterizing these candidates to dissect the
pathways by which MARF blocks cell death. This approach will allow us to understand how mitochondrial dynamics modulates Drosophila apoptosis and to
identify new components of the mitochondrial fission/fusion machinery.
305B
The
corp
gene regulates cell fate following DNA damage.
Riddhita Chakraborty, Kent Golic. Department of Biology, University of Utah, Salt Lake City,
UT.
In
Drosophila
, when somatic cells experience telomere loss, a form of DNA damage that cannot be repaired by conventional mechanisms, most cells die.
However, a few do survive. We used the BARTL (Bar and Telomere Loss) assay, which provides a rapid assessment of cell fate after telomere loss, to
screen for EP elements that modify cell fate.
The BARTL assay relies on FLP-mediated recombination to induce dicentric chromosome formation on a
Y
chromosome, just proximal to the
Bar of
Stone
(
B
S
) mutation. When the cell divides, the dicentric chromosome typically breaks, delivering a chromosome lacking a telomere to each daughter cell.
The
B
S
mutation, now present on an acentric chromosome, is lost from at least some of the daughter cells. In wildtype flies, when FLP is expressed from the
eyeless promoter, the eyes of the adults are larger than
B
S
eyes (though still smaller than wildtype) owing to survival, proliferation and differentiation of
some cells carrying a chromosome that has lost a telomere. We identified
corp
(
companion of reaper
) as a gene whose overexpression makes eyes much
larger than the control in the BARTL assay, resulting in essentially wildtype eye size. Knockdown of
corp
gene function, via RNAi, produced the opposite
effect, eliminating the eye entirely. Furthermore, we found that when corp is over-expressed in the developing eye by the
GMR
driver, it suppresses the small
eye phenotype resulting from expression of pro-apoptotic genes
hid
or
reaper
. Finally, ubiquitous
corp
overexpression increases organismal viability
following irradiation.
The
corp
gene is one of many transcriptional targets of the
p53
tumor suppressor. Other targets include genes that mediate apoptosis and DNA repair. The
specific function of
corp
is unknown, but it appears to be predominantly associated with components of the proteasome (DPIM,
https://interfly.med.harvard.edu/). We propose that
corp
targets specific cellular proteins for degradation, resulting in reduced apoptosis. Possible targets
include caspases and p53.
306C