|
Genetic control of programmed cell death (apoptosis) in Drosophila
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 backgrounds, 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
Sathyanarayana P, Barthwal MK, Kundu CN, Lane ME, Bergmann A, Tzivion G, Rana A (2002) Activation of the Drosophila MLK by ceramide reveals TNF-α
and ceramide as agonists of mammalian MLK3. Molecular Cell 10:1527-1533.
Werz C, Lee TV, Lee PL, Lackey M, Bolduc C, Stein DS, Bergmann A (2005) Mis-specified cells die by an active gene-directed process, and inhibition of this death results
in cell fate transformation in Drosophila. Development 132:5343-5452.
Cashio P, Lee TV, Bergmann A (2005) Genetic control of programmed cell death in Drosophila melanogaster. Seminars in Cell and Developmental Biology 16:225-235.
Xu D, Li Y, Arcaro M, Lackey M, Bergmann A (2005) The CARD-carrying caspase Dronc is essential for most, but not all, developmental cell death in Drosophila.
Development 132:2125-2134.
Mendes CS, Arama E, Brown S, Scherr H, Srivastava M, Bergmann A, Steller H, Mollereau B (2006) Cytochrome c-d regulates developmental apoptosis in the Drosophila
retina. EMBO Reports 7:933-939.
Bergmann A (2006) IKKε signaling: not just NF-κB. Current Biology 16:R588-R590.
Arama E, Bader M, Srivastava M, Bergmann A, Steller H (2006) The two Drosophila cytochrome C proteins can function in both respiration and caspase activation.
EMBO Journal 25:232-243.
Herz HM, Chen Z, Scherr H, Lackey M, Bolduc C, Bergmann A (2006) vps25 mosaics display non-autonomous cell survival and overgrowth, and autonomous apoptosis.
Development 133:1871-1880.
Xu D, Wang Y, Willecke R, Chen Z, Ding T, 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.
Srivastava M, Scherr H, Lackey M, Xu D, Chen Z, Lu J, Bergmann A (2007) ARK, the Apaf-1 related killer in Drosophila, requires diverse domains for its apoptotic activity.
Cell Death and Differentiation 14:92-102.
Contact Information
- Andreas Bergmann, Ph.D.
- Department of Biochemistry & Molecular Biology
- The University of Texas M.D. Anderson Cancer Center
- 1515 Holcombe Blvd. - Unit 1000
- Houston, Texas 77030, U.S.A.
- Tel: (713) 834-6294
- Fax: (713) 834-6291
- E-mail: andreas@bergman.net
|
