Shaham S (2023) Curr Biol "Shai Shaham."

Shaham S

[Curr Biol, 2023]

Interview with Shai Shaham, who studies glia-neuron interactions in C. elegans at The Rockefeller University.

Shaham S (2003) Cell "Apoptosis: a process with a (beta)NAC for complexity."

Shaham S

[Cell, 2003]

Most programmed cell deaths in the nematode C. elegans require ced-3 caspase activity. In a recent paper, Bloss et al. (2003) reveal a new C. elegans death inhibitor, icd-1, whose loss can promote apoptosis independently of ced-3.

Shaham S (2010) Nat Rev Neurosci "Chemosensory organs as models of neuronal synapses."

Shaham S

[Nat Rev Neurosci, 2010]

Neuronal synapses are important microstructures that underlie complex cognitive capacities. Recent studies, primarily in Caenorhabditis elegans and Drosophila melanogaster, have revealed surprising parallels between these synapses and the 'chemosensory synapses' that reside at the tips of chemosensory cells that respond to environmental stimuli. Similarities in the structures, mechanisms of action and specific molecules found at these sites extend to the presynaptic, postsynaptic and glial entities composing both synapse types. In this article I propose that chemosensory synapses may serve as useful models of neuronal synapses, and consider the possibility that the two synapse types derive from a common ancestral structure.

Shaham S (2009) PLoS One "galign: a tool for rapid genome polymorphism discovery."

Shaham S

[PLoS One, 2009]

BACKGROUND: Highly parallel sequencing technologies have become important tools in the analysis of sequence polymorphisms on a genomic scale. However, the development of customized software to analyze data produced by these methods has lagged behind. METHODS/PRINCIPAL FINDINGS: Here I describe a tool, 'galign', designed to identify polymorphisms between sequence reads obtained using Illumina/Solexa technology and a reference genome. The 'galign' alignment tool does not use Smith-Waterman matrices for sequence comparisons. Instead, a simple algorithm comparing parsed sequence reads to parsed reference genome sequences is used. 'galign' output is geared towards immediate user application, displaying polymorphism locations, nucleotide changes, and relevant predicted amino-acid changes for ease of information processing. To do so, 'galign' requires several accessory files easily derived from an annotated reference genome. Direct sequencing as well as in silico studies demonstrate that 'galign' provides lesion predictions comparable in accuracy to available prediction programs, accompanied by greater processing speed and more user-friendly output. We demonstrate the use of 'galign' to identify mutations leading to phenotypic consequences in C. elegans. CONCLUSION/SIGNIFICANCE: Our studies suggest that 'galign' is a useful tool for polymorphism discovery, and is of immediate utility for sequence mining in C. elegans.

Shaham S (2007) PLoS One "Counting mutagenized genomes and optimizing genetic screens in Caenorhabditis elegans."

Shaham S

[PLoS One, 2007]

In genetic screens, the number of mutagenized gametes examined is an important parameter for evaluating screen progress, the number of genes of a given mutable phenotype, gene size, cost, and labor. Since genetic screens often entail examination of thousands or tens of thousands of animals, strategies for optimizing genetics screens are important for minimizing effort while maximizing the number of mutagenized gametes examined. To date, such strategies have not been described for genetic screens in the nematode Caenorhabditis elegans. Here we review general principles of genetic screens in C. elegans, and use a modified binomial strategy to obtain a general expression for the number of mutagenized gametes examined in a genetic screen. We use this expression to calculate optimal screening parameters for a large range of genetic screen types. In addition, we developed a simple online genetic-screen-optimization tool that can be used independently of this paper. Our results demonstrate that choosing the optimal F2-to-F1 screening ratio can significantly improve screen efficiency.

Shaham S (2006) Curr Opin Neurobiol "Glia-neuron interactions in the nervous system of Caenorhabditis elegans."

Shaham S

[Curr Opin Neurobiol, 2006]

A century and a half after first being described, glia are beginning to reveal their intricate and important roles in nervous system development and function. Recent studies in the nematode Caenorhabditis elegans suggest that this invertebrate will provide important insight into these roles. Studies of C. elegans have revealed a connection between glial ensheathment of neurons and tubulogenesis, have uncovered glial roles in neurite growth, navigation, and function, and have demonstrated roles for glia and glia-like cells in synapse formation and function. Given the conservation of basic anatomical, functional and molecular features of the nervous systems between C. elegans and vertebrates, these recent advances are likely to be informative in describing nervous system assembly and function in all organisms possessing a nervous system.

Shaham S et al. (1993) International C. elegans Meeting "Antibodies against ced-3 and ced-4: a progress report."

Horvitz HR, Shaham S

[International C. elegans Meeting, 1993]

Shaham S et al. (1993) Worm Breeder's Gazette "Ectopic Expression of ced-3 and ced-4 Can Kill Cells"

Shaham S, Horvitz HR

[Worm Breeder's Gazette, 1993]

We have been analyzing the ability of constructs containing fusions of the ced-3 and ced-4 cDNAs to different promoters to kill cells in which these promoters are active. We have used promoters for the mec-7 gene (expressed in the touch cells and a few other cells; A. Fire, M. Hamelin, and J. Culotti, personal communication), the unc-30 gene (expressed in the VD and DD neurons; Y. Jin, personal communication), and the heat-shock promotor (expressed throughout the animal; A. Fire, P. Candido, personal communication). We initially examined integrated lines containing both a mec-7 -ced-3 and a mec-7 -ced-4 construct in ced-9 (n2812);ced-3 (n717)animals to avoid any potential inhibitory effects of ced-9 .We found that the touch cells were missing in these animals. By observing the cell lineages of QL and its progeny we found that PVM and occasionally SDQL undergo a cell death process that is morphologically indistinguishable from normal programmed cell deaths. The mec-7 promoter we have been using is active in both PVM and SDQL. These results support the idea suggested by mosaic analysis of ced-3 and ced-4 (Yuan and Horvitz, Developmental Biology, 138, 33-41 1992) that these genes act cell-autonomously to kill cells, since we never observed any dying cells near PVM or SDQL. These results also suggest that the machinery necessary for engulfment of cell corpses is either constitutively present or is induced by the activities of ced-3 and ced-4 ,since engulfment of corpses was generally normal. In one case we directly observed the hypoderm engulfing a dying PVM. To elucidate interactions among ced-3 ,ced-4 ,and ced-9 ,we have begun to analyze the effects of the constructs described above in various genetic backgrounds. So far we have found that introducing these constructs into animals of different genetic backgrounds has different effects. Killing of target cells is more efficient in the absence of endogenous ced-9 ,since ced-3 fusions kill more efficiently in ced-9 (n2812);ced-3 (n717)animals than in ced-3 (n717)animals, and ced-4 fusions kill more efficiently in ced-4 (n1162)ced-9 (n2812)animals than in ced-4 (n1162)animals. We also found that the mec-7 -ced-3 fusions kill less efficiently in the ced-4 (n1162)ced-9 (n2812)background than in the ced-9 (n2812);ced-3 (n717)background and that mec-7 -ced-4 fusions kill less efficiently in the ced-9 (n2812);ced-3 (n717)background than in the ced-4 (n1162)ced-9 (n2812)background. These results suggest that ced-3 function is augmented by ced-4 function and vice versa and also suggest that ced-3 and ced-4 are normally expressed in the touch cells even though these cells normally do not die. Finally, we would like to suggest that ced-3 and ced-4 can be used to genetically ablate cells in which a given promoter is active, and in the near future we hope to make available convenient vectors that can be used with any promoter.

Shaham S et al. (1992) Worm Breeder's Gazette "Molecular Analysis of the Cell Death Gene ced-3"

Horvitz HR, Shaham S

[Worm Breeder's Gazette, 1992]

MOLECULAR ANALYSIS OF THE CELL DEATH GENE ced-3 Shai Shaham and Bob Horvitz ~lMI, Dept. Biology, MIT, Cambridge, MA 02139

Shaham S (2006) Proc Natl Acad Sci U S A "Worming into the cell: viral reproduction in Caenorhabditis elegans."

Shaham S

[Proc Natl Acad Sci U S A, 2006]