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.

Ganne, Akshatha et al. (2021) International Worm Meeting "14-3-3 and its interacting proteins in aging and neurodegeneration"

Ganne, Akshatha, Balasubramaniam, Meenakshisundaram, Reis, Robert Shmookler, Ayyadevara, Srinivas

[International Worm Meeting, 2021]

The 14-3-3 proteins are an evolutionarily conserved family of proteins that are ubiquitous from nematodes to humans. They are intrinsically unstructured proteins that bind to a diverse array of key regulatory-protein targets, modulating their functions. They were shown to bind to DAF-16 and SIR-2.1 proteins, with substantial effects on C.elegans lifespan. In mammals, these regulatory proteins are most highly expressed in brain/cerebral tissue, predominantly in neurons. Their presence in cerebrospinal fluid may serve as biomarkers of neuronal damage associated with Alzheimer's disease (AD), Creutzfeldt-Jakob disease (CJD), spongiform encephalitis, brain cancers, and stroke. We also observed a significant enrichment of specific 14-3-3 isoforms among the proteins we identified in neuropathy-associated protein aggregates. Intriguingly, the interacting partners of 14-3-3 isoforms are altered in AD. We pursued these observations in the present study, by immunoprecipitation to isolate specific aggregate types, followed by mass spectrometry to identify interacting protein partners of 14-3-3, and thus to gain insights into their roles in C.elegans aging and models of age- associated neurodegeneration.

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

Gerami B et al. (1997) International C. elegans Meeting "MAPPING QUANTITATIVE TRAIT LOCI FOR CHEMOTAXIS: CORRESPONDENCE BETWEEN QTL AND odr CANDIDATE LOCI"

Phillips PC, Gerami B, Morphew JJ

[International C. elegans Meeting, 1997]

Understanding the genetics of complex traits is challenging because it can be difficult to separate out the effects of the numerous genes affecting the trait. C. elegans can serve as a useful model system for studying complex traits because of the wealth of genetic and functional information available. Chemotaxis provides an ideal trait for this type of study because it ecologically important to the nematodes, as well as likely to be influenced by many genes (a number of which are known). In collaboration with Thomas Johnson and David Shook [1] and Robert Shmookler Reis and Robert Ebert [2], who provided genotyped lines generated in a cross between N2 and BO, we have assayed the chemotaxic response of 180 recombinant inbred lines to benzaldehyde at two concentrations. These concentrations, 50 nl and 500 nl, respectively lead to an attraction or repulsion response. Separate analysis of the lines from the two labs yield different results. The SR lines show a QTL mapping to the fourth chromosome, whereas the TJ lines show several QTL, primarily on the X chromosome. The QTL on X map to the same locations as two mutants known to block the response to benzaldehyde, odr-1 and odr-5 [3]. We are in the process of evaluating these candidate loci as the actual QTL using backcrossing and complementation testing approaches. Our hope is to create a model system for studying a variety of quantitative genetic questions. [1] Genetics 142:801 (1996), [2] Genetics 135:1003 (1993), [3] Bargmann et al., Cell 74:515 (1993)

Suri, Pooja et al. (2015) International Worm Meeting "Role of aggregation-prone proteins in age-related disease."

Suri, Pooja, Alla, Ramani, Reis, Robert Shmookler, Balasubramaniam, Meenakshisundaram, Ayyadevara, Srinivas

[International Worm Meeting, 2015]

Protein aggregation is caused by a multitude of factors; there could be specific environmental causes like oxidative stress, or a genetic predisposition to aggregation. Protein aggregation increases with aging, as the ability to rectify or clear misfolded proteins is reduced. This is partly due to age-dependent deterioration in the ubiquitin/proteasomal system or other unfolded protein response systems. Aggregation will be enhanced when a misfolded, dysfunctional protein does not undergo degradation via normal pathways like autophagy/lysosome or ubiquitin proteasome-mediated degradation pathways. By mass spectrometry, we identified several proteins in the aggregates of a C. elegans model of Huntington's Disease. The effects on protein aggregation, of RNAi-mediated knockdown of some of these proteins, were tested. Some of the gene knock downs by RNAi altered the extent of aggregation in C. elegans, suggesting that these could act as seed proteins and enhance the progression of aggregates. These can be useful targets to disrupt the aggregates and could be exploited for therapeutic interventions in neurological 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

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

van Swinderen B et al. (1995) International C. elegans Meeting "INTER-BEHAVIORAL QTL STUDY OF ANESTHETIC RESPONSE"

van Swinderen B, Crowder CM

[International C. elegans Meeting, 1995]

We are studying the behavior genetics of anesthesia in C. elegans by using Recombinant Inbred(RI) lines. Based on electrophysiologic studies in vertebrates, the response to anesthetics may involve several genes. Genetic polymorphisms created by mosaic Bristol (N2) and Bergerac (BO) genomes provide an alternative to classical mutagenesis for mapping such loci. Two sets of RIs were examined in a preliminary study of select behaviors (these RIs, kindly provided by Tom Johnson" !Affiliation "[1] and Robert Shmookler Reis" !Affiliation "[2], are already genotyped for Tc1 polymorphic markers). Chemotaxis and other C. elegans behaviors have been shown to be significantly more sensitive than mobility to the volatile anesthetic halothane." !Affiliation "[3] An inter-behavioral Quantitative Trait Loci (QTL) analysis of anesthetic response was initiated by generating dose-response curves for 40 RIs for chemotaxis and mobility. The RIs were polymorphic for both behaviors in halothane: EC50 values for chemotaxis derived from dose-response curves for each RI strain ranged from 0.08 to 1.82 vol % halothane, while the N2 strain had an EC50 of 0.49=B10.064. About one-fourth of the RIs were significantly more sensitive than N2, and a few were more resistant to halothane's effect on chemotaxis. The same RIs were assayed for immobility, and the EC50 range was found to be 3.0 to 5.6 vol % halothane; the EC50 for N2 is 3.58=B10.069. Surprisingly, most RIs tested for immobility were found to be more resistant than N2. Further, patterns of sensitivity and resistance to halothane in the various RIs did not necessarily correlate between the immobility and chemotaxis assays, suggesting that different QTLs may be involved in the different behavioral effects of anesthetics. Marker correlations with EC50s suggest inter-behavioral QTL overlaps on chromosomes II and III, but a mobility-specific QTL on chromosome V. Synthetic gene interactions between N2 and BO alleles appear to be an important factor in creating phenotypic variability in the RIs. 1 Behav. Gen.16(#1): 221-235 (1986). 2 Genetics 135: 1003-1010 (1993). 3 WBG 13(#3): 76 (1994).

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