We are utilizing the highly accessible genetic model system Drosophila
melanogaster to gain a comprehensive understanding
of the biological principles that underlie the regulation
of apoptosis in the context of a multicellular organism.
In Drosophila, a large number of cells die during development
in a similar manner as in vertebrates. Therefore, molecular genetic
studies in Drosophila promise considerable potential for
advancing our understanding of the basic control mechanisms involved
in the regulation of apoptosis in vertebrates including humans.
Knowledge obtained in these studies may provide new insights into
diseases that are associated with altered rates of apoptosis.
Two major projects are currently under study in the lab.
- We have developed a novel genetic screening method
to identify genes involved in cell death control
and execution in Drosophila. However,
unexpectedly, we also identified genes involved
in growth control, signal transduction and tumor
suppression. These interesting genes
and their role in normal development are currently
under intensive study in the lab.
- We are also interested to determine why cells
die when they develop abnormally.
Apparently, an unknown mechanism monitors the
cell’s ability to develop correctly, and
activates the apoptotic program if it fails to
do so. There is virtually nothing known about
the underlying mechanisms of this process. We
are using several approaches to identify these
mechanisms including gene array analysis, genetic
screening and promoter analysis.
A tutorial in our lab will provide a detailed introduction
into modern Drosophila techniques with
emphasis on visualizing gene activity and cell death in wild-type and
various mutant background, phenotypic analysis, generating transgenic
flies and small scale genetic screens. In addition, students will gain
experience in basic molecular biology and protein chemistry. The experiments
will be aided by state-of-the-art facilities.
Selected publications
- Srivastava M, Scherr H, Lackey M, Xu D, Chen Z, Lu J, and Bergmann
A (2007)
ARK, the Apaf-1 related killer in Drosophila,
requires diverse domains for its activity. Cell Death and
Differentiation 14:92–102.
- Xu D, Wang Y, Willecke R, Chen Z, Ding T, and Bergmann A (2006)
The effector caspases drICE and dcp-1 have
partially overlapping functions in the apoptotic
pathway in Drosophila. Cell
Death and Differentiation 13:1697–1706.
- Herz, H-M., Chen, Z., Scherr, H., Lackey, M., Bolduc, C. and
Bergmann, A. (2006) vps25 mosaics
display non-autonomous cell survival and overgrowth,
and autonomous apoptosis. Development 133:1871–1880.
- Arama E, Bader M, Srivastava M, Bergmann A and
Steller H (2006) The two Drosophila cytochrome
c proteins can function in both respiration and
caspase activation. EMBO J. 25:232–243.
- Bergmann, A. (2006). IKKε: Not just
NF-κB. Current Biology 16:R588–R590.
- Mendes CS, Arama E, Brown S, Scherr H, Srivastava M, Bergmann
A, Steller H and Mollereau B (2006) Cytochrome-c-d
regulates developmental apoptosis in the Drosophila retina.
EMBO Reports 7:933–939.
- Xu D, Li Y, Arcaro M, Lackey M and Bergmann
A (2005)
The CARD-carrying caspase Dronc is essential
for most, but not all, developmental cell death
in Drosophila. Development 132:2125–2134.
- Cashio P, Lee TV and Bergmann A (2005)
Genetic Control of Programmed Cell Death in Drosophila
melanogaster.
Seminars in Cell & Developmental Biology 16:225–35.
- Werz C, Lee TV, Lee PL, Lackey M, Stein DS and Bergmann
A (2005)
Mis-specified cells die by an active gene-directed
process, or undergo developmental transformation
by suppression of cell death in Drosophila. Development 132:5343–5352.
- Sathyanarayana P, Barthwal MK, Kundu CN, Lane ME,
Bergmann A, Tzivion G and Rana A (2002) Activation
of the Drosophila MLK
by ceramide reveals TNF-a and ceramide as agonists
of mammalian MLK3. Molecular Cell 10:1527–1533.
- Bergmann A, Tugentman M, Shilo B-Z and Steller
H (2002).
Regulation of Cell Number by MAPK-dependent
control of apoptosis: a mechanism for trophic
signaling. Developmental Cell 2:159–170.
- Bergmann A (2002). Survival Signaling goes BAD. Developmental
Cell 3:607–608.
- Bergmann A, Agapite J, McCall K, and Steller H
(1998). The
Drosophila gene hid is a direct molecular
target of Ras-dependent Survival Signaling. Cell 95:331–341.
Mailing Address:
Department of Biochemistry and Molecular Biology, Unit 1000
U.T. M .D. Anderson Cancer Center
1515 Holcombe Boulevard
Houston, TX 77030
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