Martin Jaeggi et al. (2001) International C. elegans Meeting "RNA interference, a way to check for inhibitors involved in germline cell death in Caenorhabditis elegans"

Michael O Hengartner, Ravi Kamath, Andrea Calixto, Stuart Milstein, Maruxa Martinez-Campos, Julie Ahringer, Martin Jaeggi, Andy Fraser, Peder Zipperlen

[International C. elegans Meeting, 2001]

In addition to the role that programmed cell death plays during development in C. elegans , we have shown that germ cells undergo programmed cell death. Unlike somatic cells, germ cells in C. elegans do not have a fixed lineage in which each cell has a certain fate - in the germ line cell survival and cell death occurs stochastically. These cell deaths, like those in the soma, are dependent on the genes of the core apoptotic machinery: ced-9 , ced-4 and ced-3 . Interestingly, the pro-apoptotic gene egl-1 (egg-laying defective), which is upstream of ced-9 , is required for cell death in the soma, but not in the germ line, suggesting that some other factor(s) may be involved in the commitment to die. We started a screen to identify other genes that affect germ cell death. Genetic interference mediated by double-stranded RNA (RNAi) is a valuable tool for the analysis of gene function in C. elegans . By analysis of chromosome I we have found several genes involved in germ line cell death. In the future we would like to test the whole genome for genes involved in germ cell death by RNAi. Prospective candidates will then be tested in different mutant backgrounds to characterize interaction with known members of the core apoptotic machinery.

Bowerman BA et al. (1994) Worm Breeder's Gazette "The Maternal Gene skn-4 and the Specification of Ventral Blastomere Fates in the Early C. elegans Embryo"

Bowerman BA, Shelton CA, Thorpe CJ, Martin PR

[Worm Breeder's Gazette, 1994]

THE MATERNAL GENE SKN-4 AND THE SPECIFICATION OF VENTRAL BLASTOMERE FATES IN THE EARLY C. ELEGANS EMBRYO Bruce Bowerman, Paula R. Martin, Christopher J. Thorpe, and Christopher A. Shelton. The Institute of Molecular Biology, University of Oregon, Eugene, OR 97403.

Zimmer M (2009) Chem Soc Rev "GFP: from jellyfish to the Nobel prize and beyond."

Zimmer M

[Chem Soc Rev, 2009]

On December 10, 2008 Osamu Shimomura, Martin Chalfie and Roger Tsien were awarded the Nobel Prize in Chemistry for "the discovery and development of the green fluorescent protein, GFP". The path taken by this jellyfish protein to become one of the most useful tools in modern science and medicine is described. Osamu Shimomura painstakingly isolated GFP from hundreds of thousands of jellyfish, characterized the chromophore and elucidated the mechanism of Aequorean bioluminescence. Martin Chalfie expressed the protein in E. coli and C. elegans, and Roger Tsien developed a palette of fluorescent proteins that could be used in a myriad of applications.

Hall DH et al. (1994) Worm Breeder's Gazette "Cytology of Degenerin-Induced Cell Death in the PVM Neuron"

Driscoll MA, Chalfie M, Gu GQ, Hall DH, Gong L

[Worm Breeder's Gazette, 1994]

Cytology of degenerin-induced cell death in the PVM neuron David H. Hall, Guoqiang Gu+, Lei Gong#, Monica Driscoll#, and Martin Chalfie+, * Dept. Neuroscience, Albert Einstein College of Medicine, Bronx, N.Y. 10461 + Dept. Biological Sciences, Columbia University, New York, N.Y. 10027 # Dept. Molecular Biology and Biochemistry, Rutgers University, Piscataway, N.J. 08855

Ray C et al. (1990) Worm Breeder's Gazette "CORRECTION Isolation of a C. elegans Cysteine Protease Gene"

McKerrow JH, Ray C

[Worm Breeder's Gazette, 1990]

In the previous issue of the WBG (Vol. 11, #3, page 20) we reported the isolation of a cysteine protease clone from a mixed-stage C. elegans cDNA library. This library was originally obtained from Chris Martin and not from Cynthia Kenyon as was reported in the article. Our apologies for any misunderstanding caused by this oversight.

Goto S (1999) Journal of Gerontology "Commentary on "Protein carbonyl accumulation in aging Dauer formation-defective (daf) mutants of Caenorhabditis elegans"."

Goto S

[Journal of Gerontology, 1999]

In recent years, oxidative damage to macromolecules has gained popularity as the basis of the molecular mechanism of aging. Martin proposes oxidative damage to macromolecules as one of the major public mechanisms of aging. Interest in modifications of protein by reactive oxygen species in aging was apparently introduced by Stadtman. Although various types of oxidative modifications can occur in proteins, carbonyl residues believed to be generated by metal catalyzed reaction or otherwise introduced by lysine, arginine and/or proline residues in vivo are often used as a marker of direct or

Hampoelz B et al. (2004) Cell "Heterotrimeric G proteins: new tricks for an old dog."

Knoblich JA, Hampoelz B

[Cell, 2004]

Heterotrimeric G proteins are well known for their function in signal transduction downstream of seven transmembrane receptors. More recently, however, genetic analysis in C. elegans and in Drosophila has revealed a second, essential function of these molecules in positioning the mitotic spindle and attaching microtubules to the cell cortex. Five new publications in Cell (Afshar et al., 2004; Du and Macara, 2004 [this issue of Cell]; Hess et al., 2004), Developmental Cell (Martin-McCaffrey et al., 2004), and Current Biology (Couwenbergs et al., 2004) show that this function is conserved in vertebrates and-like the classical pathway- involves cycling of G proteins between GDP and GTP bound conformations.

Guillaume Lettre et al. (2002) East Coast Worm Meeting "Genome-wide RNAi screen for genes that control germ cell apoptosis in the nematode C. elegans"

Julie Ahringer, Andrea Calixto, Martin Jaeggi, Ravi Kamath, Ekaterini Kritikou, Michael O Hengartner, Andrew Fraser, Guillaume Lettre

[East Coast Worm Meeting, 2002]

Apoptosis can be defined as a physiological mechanism that removes unneeded, harmful, or damaged cells in a regulated manner. It has important developmental functions, and mis-regulation of apoptosis has been associated with various pathologies (e.g. cancer, strokes, neurodegenerative disorders, etc.). Apoptosis is part of the normal developmental program of the nematode C. elegans: out of the 1090 somatic cells that are born in a hermaphrodite, exactly 131 will die by apoptosis. Several genetic screens have identified genes required for somatic cell death in the worm. Apoptosis also occurs stochastically in the C. elegans germ line. Although the core apoptotic machinery is the same for physiological germ cell death than for somatic cell death, genetic studies have shown that the regulators are different. Indeed, the BH3 domain protein EGL-1 is essential for cell death in the soma, but is not required for germ line apoptosis. In order to identify genes that regulate physiological germ cell death in C. elegans, we undertook a genome-wide RNAi screen. We have completed our primary screen of the C. elegans genome (~16,700 genes), and have found several dozen genes that cause more germ cell deaths when inactivated by RNAi. We expect that sequence analysis of these candidates and epistatic analyses will allow us to categorize them into functional groups, with the ultimate goal of better understanding the different pathways that might regulate physiological germ cell death.

Guillaume Lettre et al. (2002) European Worm Meeting "Genome-wide RNAi screen for genes that control germ cell apoptosis in C. elegans"

Andrea Calixto, Michael O Hengartner, Guillaume Lettre, Ekaterini Kritikou, Julie Ahringer, Martin Jaeggi, Andy Fraser, Ravi Kamath

[European Worm Meeting, 2002]

Programmed cell death (apoptosis) is an important component of animal development and homeostasis. Apoptosis is an efficient way to physiologically eliminate cells in multicellular organisms and it is a major regulatory feature of embryonic development, establishment of immune self-tolerance and regulation of tissue homeostasis in mammals. Changes in the levels of apoptosis have been implicated in the pathology of many diseases, including cancer, autoimmune diseases, stroke, neuro-degenerative disorders, myocardial infraction and AIDS. Each of the key C.elegans cell death genes has one or several mammalian homologues, suggesting that the apoptotic machinery identified in C.elegans is evolutionarily conserved. While work over the last few years has shed light on key players, proteins controlling the apoptotic machinery and the effector mechanisms that mediate cell death, little is known about the regulatory signals by which a cell controls its suicide machine. We propose that these upstream regulatory pathways are also conserved, such that an analysis of these pathways in C. elegans will, indirectly, also shed light on how apoptosis is regulated in humans. Almost 50% of predicted C. elegans genes have a significant human match including many genes implicated in human disease and functional analysis of the C.elegans genome has shed light on many conserved biological processes and molecular pathways. Germ cells can undergo apoptosis in response to a physiological pathway that is used to limit germ cell numbers during oogenesis as well as a checkpoint pathway that activates the apoptotic machinery in response to DNA damage. To understand the molecular basis of germ cell apoptosis we are currently using "genome-wide RNA-mediated interference (RNAi)" to systematically screen the C.elegans genome for genes that participate in the regulation of germ cell death. Germ line apoptosis is determined by acridine orange staining/fluorescent microscopy and confirmed by Nomarski microscopy. Using C. elegans as a model for genes that participate in the regulation of germ cell death will enhance our understanding of the genetic basis of the apoptotic machinery. Furthermore, it will enable us to elucidate specific genetic responses associated with the global changes that occur during apoptosis.

Tokuoka SM et al. (2008) Mol Biol Cell "The mood stabilizer valproate inhibits both inositol- and diacylglycerol-signaling pathways in Caenorhabditis elegans."

Tokuoka SM, Saiardi A, Nurrish SJ

[Mol Biol Cell, 2008]

Monitoring Editor: Tom U. Martin The anti-epileptic valproate (VPA) is widely used in the treatment of bipolar disorder, although the mechanism of its action in the disorder is unclear. We show here that VPA inhibits both inositol phosphate and diacylglycerol (DAG) signaling in C.elegans. VPA disrupts two behaviors regulated by the inositol 1,4,5-Tris phosphate (IP3): defecation and ovulation. VPA also inhibits two activities regulated by DAG signaling: acetylcholine (ACh) release and egg-laying. The effects of VPA on DAG signaling are relieved by phorbol ester, a DAG analog, suggesting that VPA acts to inhibit DAG production. VPA reduces levels of DAG and IP1, but PIP2 is slightly increased, suggesting that Phospholipase C mediated hydrolysis of PIP2 to form DAG and IP3 is defective in the presence of VPA.