Kreeger KY (1996) The Scientist "Hot papers: Programmed cell death."

Kreeger KY

[The Scientist, 1996]

Biologist H. Robert Horvitz discusses the genetics of cell death in the nematode C. elegans.

Thomas JH et al. (1994) Worm Breeder's Gazette "lin-36, a Class B Synthetic Multivulva Gene, Encodes a Novel Protein"

Thomas JH, Horvitz HR

[Worm Breeder's Gazette, 1994]

lin-36, a Class B Synthetic Multivulva Gene, Encodes a Novel Protein Jeffrey H. Thomas and H. Robert Horvitz, HHMI, Dept. Biology, MIT, Cambridge, MA 02139, USA

Mano, Itzhak et al. (2009) International Worm Meeting "Molecular Analysis of Glutamate Transporters and Excitotoxic Neurodegeneration in C. elegans."

Driscoll, Monica, Mano, Itzhak, Kalb, Robert

[International Worm Meeting, 2009]

Glutamate (Glu) is the main excitatory neurotransmitter in humans and a key transmitter in nematodes. Glu synaptic concentrations are carefully controlled by a special uptake system, the Glu Transporters (GluTs). Insufficient activity of GluTs (seen in stroke and a range of neurodegenerative diseases) causes Glu accumulation, exaggerated stimulation of the post-synaptic cell, and excitotoxic neurodegeneration. We study the regulation of normal and abnormal Glu neurotransmission at three levels: 1) We analyze the regulation of normal synaptic activity by GluTs: We find that nematodes use an unusual strategy to eliminate Glu that has been released into synapses. This strategy relays heavily on remote uptake of Glu, an intriguing approach to controlling synaptic function. 2) We study the molecular events that lead from the pathological accumulation of Glu in the synapse to the demise of the affected neurons. We combined Dglt-3, a GluT-null mutation, with activated-Gas* expression to trigger excitotoxicity. We find that neurodegeneration is mediated by Ca2+-permeable Glu receptors of the AMPA subtype and by a calcineurin-regulated adenylyl cyclase. This novel functional interaction can be recapitulated using mammalian proteins expressed in Xenopus oocyes, suggesting a new view on potential neurodegenerative mechanisms in excitotoxicity. 3) We study the ability of stress-resistance signaling pathways to protect from excitotoxic neurodegeneration. We find that a central signaling pathway that confers stress resistance also reduces the susceptibility of neurons to excitotoxicity. Together these observations highlight the ability of C. elegans studies to provide new insights into decisive events in the processes that mediate neuronal physiology and pathology, and to provide new inroads to understand the mechanism of critical human diseases.

Goff SP (1999) Cancer Research "Genetic control of programmed cell death in the nematode Caenorhabditis elegans - Introduction."

Goff SP

[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

Doshi, Shachee et al. (2015) International Worm Meeting "A role for neuropeptide signaling in regulating C. elegans response to anoxia."

Kalb, Robert G., Doshi, Shachee, Flibotte, John J.

[International Worm Meeting, 2015]

The nematode C. elegans generally prefers 8-12% environmental oxygen, but frequently encounters much lower oxygen microenvironments as it dwells in soil and rotting fruit. Although the genetic regulation of the hypoxic response has been well characterized in the worm, less is known about the response to anoxic environments. Our previous work suggests that loss of function mutants in the proprotein convertase EGL-3 (egl-3(gk238) and egl-3(ok979)), involved in neuropeptide maturation, have a significant survival advantage after 48hr anoxia compared to N2 animals. Loss of function in the calcium-dependent activator protein for secretion UNC-31 (unc-31(e169)), required for dense-core vesicle secretion, similarly have significantly greater survival after anoxia. Previous work also confirms reports in the literature that loss of insulin signaling (daf-2(e1370)) is protective against anoxia, and that this occurs in a daf-16 dependent manner. Here, we confirm our results with neuropeptide pathway mutants and show that egl-3(ok979);daf-16(mgDf50) as well as unc-31(e169);daf-16(mgDf50) double mutants resist anoxic insults at levels similar to neuropeptide signaling mutants alone. These results suggest that neuropeptide signaling confers vulnerability to worms experiencing anoxic stress, and that this effect is at least partially independent of the daf-2/daf-16 insulin-like signaling pathway. Future work aims to define the relevant neuropeptide(s) and associated signaling mechanisms, as well as the cell-types elaborating the neuropeptides responsible for neuropeptide-mediated death under anoxia. .

Chen X et al. (2015) Mol Neurodegener "Erratum to: Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression."

McCue HV, Chen X, Morgan A, Kashyap SS, Barclay JW, Kraemer BC, Burgoyne RD, Wong SQ

[Mol Neurodegener, 2015]

The original version of this article [1] unfortunately contained a mistake. The author list contained a spelling error for the author Hannah V. McCue. The original article has been corrected for this error. The corrected author list is given below:Xi Chen, Hannah V. McCue, Shi Quan Wong, Sudhanva S. Kashyap, Brian C. Kraemer, Jeff W. Barclay, Robert D. Burgoyne and Alan Morgan

Casey DL (1999) Human Genome News "International team delivers C. elegans sequence."

Casey DL

[Human Genome News, 1999]

For the first time, scientists have the nearly complete genetic instructions for an animal that, like humans, has a nervous system, digests food, and reproduces sexually. The 97-million-base genome of the tiny roundworm Caenorhabditis elegans was deciphered by an international team led by Robert Waterston and John Sulston. The work was reported in a special issue of the journal Science (December 11, 1998) that featured six articles describing the history and significance of the accomplishment and some early sequence-analysis results.

Brownlee DJA et al. (1996) Parasitol Today "Nematode neuropeptides: Localization, isolation and functions."

Holden-Dye L, Brownlee DJA, Walker RJ, Fairweather I

[Parasitol Today, 1996]

Historically, peptidergic substances (in the form of neurosecretions) were linked to moulting in nematodes. More recently, there has been a renewal of interest in nematode neurobiology, initially triggered by studies demonstrating the localization of peptide immunoreactivities to the nervous system. Here, David Brownlee, Ian Fairweather, Lindy Holden-Dye and Robert Walker will review progress on the isolation of nematode neuropeptides and efforts to unravel their physiological actions and inactivation mechanisms. Future avenues for research are suggested and the potential exploitation of peptidergic pathways in future therapeutic strategies

Marx JL (1984) Science "New clues to developmental timing."

Marx JL

[Science, 1984]

Within the past few years researchers have finally begun to be able to peer inside a hitherto impenetrable black box, namely, the development of complex organisms. The genes that control the commitment of embryonic cells to specific fates are now being found and characterized. A case in point is reported in this issue of Science (p. 409). Victor Ambros of Harvard University and H. Robert Horvitz of Massachusetts Institute of Technology have identified genes that affect the timing of developmental events in the roundworm Caenorhabditis elegans.

Barbour V (2002) Lancet "Celebrating death--the 2002 Nobel prize in physiology or medicine."

Barbour V

[Lancet, 2002]

The overwhelming complexity of higher organisms can make it hard to know where to begin to understand them. The three scientists who share this year's Nobel prize for physiology or medicine, Sydney Brenner (Salk Institute, La Jolla, CA, USA), John Sulston (Wellcome Trust Sanger Institute, Hinxton, UK), and Robert Horvitz (Massachusetts Institute of Technology, Boston, MA, USA), all chose to study a far simpler organisms - the nematode worm Caenorhabditis elegans. Although multicellular, this organism reproduces rapidly and is transparent, so that each developmental stage can be seen clearly without the need for dissection.