Barbara Conradt
Associate Professor of Genetics
Regulation of Programmed Cell Death in C. elegans
Programmed cell death, or apoptosis, is the physiological process through
which multicellular organisms eliminate superfluous or potentially harmful
cells from their body. Deregulated programmed cell death can lead to various
types of diseases in humans, including cancer, autoimmune diseases and
neurodegenerative diseases, which demonstrates how important this process is
for human health. Studies on the molecular mechanisms that regulate and execute
programmed cell death will help us understand the function of this process in
cellular homeostasis and its role in various pathological processes.
Most of our current knowledge of programmed cell death is based on genetic
and molecular analyses of the nematode Caenorhabditis elegans, an
organism that is especially amenable to studies on programmed cell death. These
studies revealed that the central cellular machinery employed by organisms as
diverse as C. elegans and humans to eliminate cells in a 'programmed'
manner has been conserved. Using C. elegans as a tool, the goal of our
current research is to identify pathways and mechanisms that regulate this
central cell-death machinery. In specific, using genetic and molecular
approaches, we are studying how the activity of BH3-only proteins (BH3, Bcl-2
Homology region 3), key activators of programmed cell death, are regulated
during C. elegans development. Results from these studies will
contribute to our knowledge of the molecular mechanisms of programmed cell
death not only in C. elegans but in higher organisms as well.
Publications
- Schertel, C. and Conradt, B. 2007. C. elegans orthologues of components of
the Rb tumor suppressor complex have distinct pro-apoptotic functions.
Development (in press).
- Rolland, S. and Conradt, B. 2006. The role of mitochondria in apoptosis
induction in Caenorhabditis elegans: more than just innocent bystanders? Cell
Death Differ 13:1281-1286.
- Grote, P. and Conradt, B. 2006. The PLZF-like protein TRA-4 co-operates
with the Gli-like transcription factor TRA-1 to promote female development in
C. elegans. Dev Cell 11:561-573.
- Conradt, B. 2006. Cell biology: Mitochondria shape up. Nature
443:646-647.
- Jagasia, R., Grote, P., Westermann, B., Conradt, B. 2005.
DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in
C. elegans. Nature, 433: 754-760.
- Jäger, S., Schwartz, H. T., Horvitz, H. R. and Conradt, B.
2004. The C. elegans F-box protein SEL-10 promotes female development
and may act by targeting the proteins FEM-1 and FEM-3 for degradation by the
proteasome. PNAS, 101:12549-12554.
- Hoeppner, D. J., Spector, M.S., Ratcliff, T.M., Kinchen, J. M., Granat, S.,
Lin, S.-C., Bhusri, S. S., Conradt, B., Herman, M. A., and
Hengartner, M. O. 2004. eor-1 and eor-2 are required for cell-specific
apoptotic death in C. elegans. Dev Biol, 274:125-138.
- Thellmann, M., Hatzold, J. and Conradt, B. 2003. The
Snail-like CES-1 protein of C. elegans can block the expression of the
BH3-only cell-death activator gene egl-1 by antagonizing the function of bHLH
proteins. Development, 130:4057-4071.
- Conradt, B.. 2002. With a little help from your friends:
cells don't die alone. Nature Cell Biol, 4: E139-143.
- Conradt, B.. 2001. Cell engulfment, no sooner ced than
done. Dev Cell, 1:445-447.
- Chen F., Hersh, B. M., Conradt, B., Zhou Z., Riemer, D.,
Gruenbaum, Y. and H. R. Horvitz. 2000. CED-4 Translocation to Nuclear Membranes
during C. elegans Programmed Cell Death. Science, 287:1485-1489.
- B. Conradt and H. R. Horvitz. 1999. The TRA-1 Sex
Determination Protein of C. elegans Regulates Sexually Dimorphic Cell
Deaths by Repressing the egl-1 Cell Death Activator Gene. Cell,
98:317-327.
- B. Conradt and H. R. Horvitz. 1998. The C. elegans Protein
EGL-1 is Required for Programmed Cell Death and Interacts with the Bcl-2-like
Protein CED-9. Cell, 93:519-529.
