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Cancer Research,
1999]
It is an honor and a great pleasure to introduce Dr. Robert Horvitz to you as the 1998 recipient of the Alfred Sloan Prize of the General Motors Cancer Research Foundation. Let me begin by telling you a little bit about Bob's
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Chembiochem,
2003]
I never expected to spend most of my life studying worms. However, when the time came for me to choose an area for my postdoctoral research, I was intrigued both with the problems of neurobiology and with the approaches of genetics. Having heard that a new "genetic organism" with a remarkably simple nervous system was being explored by Sydney Brenner - the microscopic soil nematode Caenorhabditis elegans - I decided to join Sydney in his efforts.
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Biochem Biophys Res Commun,
2017]
Programmed cell clearance is a highly regulated physiological process of elimination of dying cells that occurs rapidly and efficiently in healthy organisms. It thus ensures proper development as well as homeostasis. Recent studies have disclosed a considerable degree of conservation of cell clearance pathways between nematodes and higher organisms. The externalization of the anionic phospholipid phosphatidylserine (PS) has emerged as an important "eat-me" signal for phagocytes and its exposition on apoptotic cells is controlled by phospholipid translocases and scramblases. However, there is mounting evidence that PS exposure occurs not only in apoptosis, but may also be actively expressed on the surface of cells undergoing other forms of cell death including necrosis; PS is also expressed on the surface of engulfing cells. Additionally, PS may act as a "save-me" signal during axonal regeneration. Here we discuss mechanisms of PS exposure and its recognition by phagocytes as well as the consequences of PS signaling in nematodes and in mammals.
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Dev Dyn,
2010]
Axonal regeneration in Caenorhabditis elegans was first reported five years ago. Individual green fluorescent protein-labeled axons can be severed using laser microsurgery and their regrowth followed in vivo. Several neuron types display robust regrowth after injury, including motor and sensory neurons. The small size and transparency of C. elegans make possible large-scale genetic and pharmacological screens for regeneration phenotypes.
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Front Cell Dev Biol,
2023]
Phosphatidylserine (PS) is a lipid component of the plasma membrane. It is asymmetrically distributed to the inner leaflet in live cells. In cells undergoing apoptosis, phosphatidylserine is exposed to the outer surfaces. The exposed phosphatidylserine acts as an evolutionarily conserved "eat-me" signal that attracts neighboring engulfing cells in metazoan organisms, including the nematode <i>Caenorhabditis elegans</i>, the fruit fly <i>Drosophila melanogaster</i>, and mammals. During apoptosis, the exposure of phosphatidylserine to the outer surface of a cell is driven by the membrane scramblases and flippases, the activities of which are regulated by caspases. Cells undergoing necrosis, a kind of cell death frequently associated with cellular injuries and morphologically distinct from apoptosis, were initially believed to allow passive exposure of phosphatidylserine through membrane rupture. Later studies revealed that necrotic cells actively expose phosphatidylserine before any rupture occurs. A recent study in <i>C. elegans</i> further reported that the calcium ion (Ca<sup>2+</sup>) plays an essential role in promoting the exposure of phosphatidylserine on the surfaces of necrotic cells. These findings indicate that necrotic and apoptotic cells, which die through different molecular mechanisms, use common and unique mechanisms for promoting the exposure of the same "eat me" signal. This article will review the mechanisms regulating the exposure of phosphatidylserine on the surfaces of necrotic and apoptotic cells and highlight their similarities and differences.
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Medicina (B Aires),
2009]
Green fluorescent protein (GFP) is a protein produced by the jellyfish Aequorea victoria, that emits bioluminescence in the green zone of the visible spectrum. The GFP gene has been cloned and is used in molecular biology as a marker. The three researchers that participated independently in elucidating the structure and function of this and its related proteins, Drs. Shimomura, Chalfie and Tsien were awarded the Nobel Prize in Chemistry 2008. Dr. Shimomura discovered and studied the properties of GFP. Using molecular biological techniques, Chalfie succeeded in introducing the GFP gene into the DNA of the small, almost transparent worm C. elegans, and initiated an era in which GFP would be used as a glowing marker for cellular biology. Finally, Dr.Tsien found precisely how GFP's structure produces the observed green fluorescence, and succeeded in modifying the structure to generate molecules that emit light at slightly different wavelengths, which gave tags of different colors. Fluorescent proteins are very versatile and are being used in many areas, such as microbiology, biotechnology, physiology, environmental engineering, development, etc. They can, for example, illuminate growing cancer tumours; show the development of Alzheimer's disease, or detect arsenic traces in water. Finding the key to how a marine organism produces light unexpectedly ended up providing researchers with a powerful array of tools with which to visualize cell biology in action.
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Cell Mol Life Sci,
2016]
Programmed cell death is critical to the development of diverse animal species from C. elegans to humans. In C. elegans, the cell death program has three genetically distinguishable phases. During the cell suicide phase, the core cell death machinery is activated through a protein interaction cascade. This activates the caspase CED-3, which promotes numerous pro-apoptotic activities including DNA degradation and exposure of the phosphatidylserine "eat me" signal on the cell corpse surface. Specification of the cell death fate involves transcriptional activation of the cell death initiator EGL-1 or the caspase CED-3 by coordinated actions of specific transcription factors in distinct cell types. In the cell corpse clearance stage, recognition of cell corpses by phagocytes triggers several signaling pathways to induce phagocytosis of apoptotic cell corpses. Cell corpse-enclosing phagosomes ultimately fuse with lysosomes for digestion of phagosomal contents. This article summarizes our current knowledge about programmed cell death and clearance of cell corpses in C. elegans.
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Biochem Soc Trans,
2004]
IFT (intraflagellar transport) assembles and maintains sensory cilia on the dendritic endings of chemosensory neurons within the nematode Caenorhabditis elegans. During IFT, macromolecular protein complexes called IFT particles (which carry ciliary precursors) are moved from the base of the sensory cilium to its distal tip by anterograde IFT motors (kinesin-II and Osm-3 kinesin) and back to the base by retrograde IFT-dynein [Rosenbaum and Witman (2002) Nat. Rev. Mol. Cell Biol. 3, 813-825; Scholey (2003) Annu. Rev. Cell Dev. Biol. 19, 423-443; and Snell, Pan and Wang (2004) Cell 117, 693-697]. In the present study, we describe the protein machinery of IFT in C. elegans, which we have analysed using time-lapse fluorescence microscopy of green fluorescent protein-fusion proteins in concert with ciliary mutants.
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Mech Ageing Dev,
2002]
It strikes me that among our relatively small community of gerontologists concerned with genetic approaches to our science, there is somewhat of a dichotomization. On the one hand, there are those of us, like myself, who tend to be dour ''complificationists''. Journalists talk to us, but are usually disappointed by the encounter. We are perhaps too impressed with the enormous diversity of genetic modulations of human senescence and with our interpretations of the implications of the evolutionary biological theory of senescence, namely that senescent phenotypes per se are non-adaptive, non-determinative, subject to stochastic events as well as highly polygenic modulations, with resulting wide variability in mechanisms of senescence among and within species. Quite happily, however, there are wonderful optimists among us. They seem to be convinced that there are likely to be a rather small number of major gene effects for a few major mechanisms. They include most Saccharomyces cerevisiae and Caenorhabditis elegans geneticists, some Drosophila melanogaster geneticists, and some mouse geneticists. They also include caloric restriction enthusiasts. Let''s call these colleagues ''simplificationists''. Journalists and friends generally find them to be delightful companions. Where does the truth lie? Perhaps the truth lies somewhere between these two extremes and is largely dependent upon the organisms and the range of environments being investigated.
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Adv Genet,
2009]
Caenorhabditis elegans has become a model system of choice for optical approaches to cellular biology largely due to its extraordinary combination of transparency, well-defined anatomy, rapid generation time, and simple genetics. In particular, studies in nervous system development and function have benefited tremendously since C. elegans was first examined under the microscope. After the introduction of green fluorescent protein as a means of following gene expression and protein localization in living animals, a variety of optical approaches have been developed for probing and perturbing neuronal activity. Microfluidic technologies have opened new possibilities for high-resolution imaging during behavior. Femtosecond pulsed lasers allow for precise severing of individual processes in the living animal. This chapter will cover some recent methodological advances in imaging worm neurons as well as some of the many biological details of the worm nervous system revealed by these new optical approaches. Advantages and limitations of these methods will be discussed in this chapter.