McCloskey, Richard et al. (2015) International Worm Meeting "Food status regulates three behavioral states in Caenorhabditis elegans."

Fang-Yen, Christopher, McCloskey, Richard

[International Worm Meeting, 2015]

Animals switch between behavioral states to adapt to their environments, pursue goals, and to meet energy intake requirements. For example, highly active states are often associated with food or mate searching or predator avoidance while more inactive states are associated with rest or feeding. The nematode C. elegans exhibits behavior states such as dwelling, roaming, and quiescence characterized by low, high, and absent locomotory activity, respectively. It has been observed that food influences the decision to alternately roam or dwell while liquid environments promote a decision to alternate between roaming and quiescence. We investigated the possibility that these three behaviors could exist in any mechanical environment via long-term, longitudinal imaging of C. elegans behavior. We find that roaming, dwelling, and quiescence can occur regardless of the mechanical environment and that fasting induces quiescence by a regulated mechanism that likely depends on neuropeptides. We characterized feeding, locomotion, posture, and egg-laying and find that these stereotypically differ depending on the given behavioral state suggesting that behavioral states reflect the status of multiple neural circuits. We investigated how conserved food-responsive signaling pathways influence behavior state decisions and find that the foraging homolog egl-4 is regulates the architecture of behavioral dynamics while insulin-like signaling is required in the nervous system to regulate decisions over behavior state type. Overall our results show that dwelling, roaming, and fasting quiescence are not just locomotory states but distinct behavior states regulated food availability and evolutionarily conserved signaling pathways involved in nutrition. .

McCloskey, Richard et al. (2009) International Worm Meeting "The Emerging Role of Ubiquitin-Specific Protease MATH-33 in Polarity of the Caenorhabditis elegans Early Embryo."

McCloskey, Richard, Hoose, Wendy A, Morton, Diane G, Kemphues, Kenneth J

[International Worm Meeting, 2009]

The study of partitioning defective (PAR) proteins in the nematode model Caenorhabditis elegans has been instrumental in elucidating conserved mechanisms of cellular polarity. Recently, our lab has used RNAi feeding as a reverse genetic method to uncover additional genes that may be involved in cellular polarity. We found that depletion of the ubiquitin-specific protease MATH-33 increases embryonic lethality and increases the penetrance of polarity phenotypes in weak par-1(zu310ts), par-2(it5ts), and par-4(it57ts) mutants, but does not seem to increase polarity defects in weak par-3 mutants. Generally, these results indicate that MATH-33 protein functions to support polarity in the one-cell embryo, and that it may specifically function with components that are necessary for maintaining the posterior domain. Furthermore, math-33 mutation alone appears to subtly affect the distribution of posteriorly localized cellular components such as PAR-2 and P granules, indicating that its activity may contribute to their localization or activity. Lastly, an antibody created against a C-terminal fragment of MATH-33 has shown that MATH-33 is present in embryo cytoplasm, and is enriched in nuclei, indicating that it could be functioning anywhere the one-cell embryo. My future research will continue to explore the mechanism by which these subtle polarity defects arise and, will address whether MATH-33 is responsible for regulating one or more of the PARs directly.

McCloskey, Richard J. et al. (2011) International Worm Meeting "Putative De-ubiquitylating Enzymes MATH-33 and USP-47 are Required for Polarity Establishment in C. elegans."

McCloskey, Richard J., Kemphues, Kenneth

[International Worm Meeting, 2011]

The C. elegans one-cell embryo polarizes in response to a cue from the sperm centrosome, and this signal leads to a cascade of events that localizes cell fate determinants to execute the developmental program of the worm. In the course of investigating novel genes that may be involved in polarity we found that simultaneous mutation/RNAi of the genes math-33 and usp-47 leads to the inability of embryos to correctly establish and maintain asymmetry as defined by posterior and anterior markers PAR-2 and PAR-3. Protein homology indicates that MATH-33 and USP-47 are putative de-ubiquitylating enzymes whose similar structure and common expression in the germline and early embryos strongly suggests they have functional overlap. We determined that polarity phenotypes result from an impaired establishment phase in which we observe reduced PAR-2 recruitment, and a decrease or failure of posterior to anterior myosin flow. Our observations on the position of the centrosomes lead us to suggest that the centrosomal interaction with the posterior cortex is defective. The polarity defects can be suppressed by compromising the proteasome, suggesting that MATH-33 and USP-47 affect protein stability rather than protein activity. Lastly, we found that USP-46, the homolog of a DUB with a role in polarity in Schizosaccharomyces pombe, is potentially redundant with MATH-33 and USP-47, suggesting that de-ubiquitylation is a required and evolutionarily conserved mechanism to control polarity. .

Townsend SR et al. (1994) Worm Breeder's Gazette "C. elegans Molecular Genetics and Long PCR."

Finelli AL, Savage C, Xie T, Padgett RW, Townsend SR

[Worm Breeder's Gazette, 1994]

C. elegans Molecular Genetics and Long PCR Scott R. Townsend, Cathy Savage, Alyce L. Finelli, Ting Xie, and Richard W. Padgett, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08855

Martinelli SD et al. (1995) International C. elegans Meeting "ACEDB"

Durbin RM, Martinelli SD

[International C. elegans Meeting, 1995]

We hope to provide a demonstration of the current state of the ACeDB worm database on Unix workstations, and if possible Apple Macintosh, throughout the poster sessions. This will be based on the new version 4 release of the acedb software (Jean Thierry-Mieg, Richard Durbin and numerous others), which contains many new features for greater efficiency, more flexible printing, and display of new features.

(2024) Development "The people behind the papers - Thomas Mullan and Richard Poole."

[Development, 2024]

Asymmetric cell divisions can produce daughter cells of different sizes, but it is unclear whether unequal cell cleavage is important for cell fate decisions. A new paper in Development explores the role of unequal cleavages in Caenorhabditis elegans embryos. To learn more about the story behind the paper, we caught up with first author Thomas Mullan and corresponding author Richard Poole, Associate Professor of Developmental Biology at University College London, UK.

Herman RK et al. (1997) Worm Breeder's Gazette "STATUS OF THE CAENORHABDITIS GENETICS CENTER (CGC)"

Herman RK, Stiernagle TL

[Worm Breeder's Gazette, 1997]

May 31, 1997 will mark the end of our current five-year contract with the NIH National Center for Research Resources, which supports the activities of the CGC. The activities in St. Paul have involved primarily the acquisition, maintenance and distribution of stocks and information about stocks, acquisition and maintenance of the C. elegans bibliography, and publication and distribution of The Worm Breeder's Gazette (WBG) and WBG Subscriber Directory. Genetic nomenclature and the genetic map have been managed for the period 1992-1997 by Jonathan Hodgkin (CGC Map Curator) on a subcontract. Currently, the subcontract provides half of Sylvia Martinelli's salary, plus travel and minor expenses. Additional support from within the MRC Laboratory of Molecular Biology and the Sanger Centre has been used to fund other essential resources such as computer equipment, as well as Jonathan's and Richard Durbin's time. Richard has been involved in mapkeeping through his work on ACeDB. We are pleased that Jonathan, Richard and Sylvia agreed to continue their work for another five years. We have submitted an application for a new five year contract that would include a subcontract for nomenclature and mapkeeping on essentially the same terms as before. A description of the nomenclature and mapkeeping activities is given in the following abstract. We are grateful to Leon Avery for setting up our CGC gopher server and also for arranging for the electronic submission of WBG abstracts (as well as abstracts for various C. elegans meetings). His C. elegans WWW server has become an essential resource for the worm community. We were therefore pleased to include Leon (only 5% effort) in a second subcontract as part of our new CGC application. We welcome comments and suggestions about any of the CGC activities.

Kelley S (2000) Brief Bioinform "Getting started with Acedb."

Kelley S

[Brief Bioinform, 2000]

Acedb is one of the more venerable pieces of Genomics software. Acedb was originally created in 1992 by Richard Durbin and Jean Thierry-Mieg to manage the data from the Caenorhabditis elegans mapping project and subsequently the C. elegans sequencing project. From beginnings as a C. elegans-specific tool, it has been continuously developed into a flexible suite of data management, display and scripting tools providing facilities for managing and annotation mapping information and DNA and peptide sequences.This paper gives a basic overview of the Acedb suite, and step-by-step guidance on how to download and install Acedb. It is intended to take an Acedb novice to stage where they can begin to experiment and explore the facilities that are available.

Sommer RJ (2008) Bioessays "Homology and the hierarchy of biological systems."

Sommer RJ

[Bioessays, 2008]

Homology is the similarity between organisms due to common ancestry. Introduced by Richard Owen in 1843 in a paper entitled "Lectures on comparative anatomy and physiology of the invertebrate animals", the concept of homology predates Darwin's "Origin of Species" and has been very influential throughout the history of evolutionary biology. Although homology is the central concept of all comparative biology and provides a logical basis for it, the definition of the term and the criteria of its application remain controversial. Here, I will discuss homology in the context of the hierarchy of biological organization. I will provide insights gained from an exemplary case study in evolutionary developmental biology that indicates the uncoupling of homology at different levels of biological organization. I argue that continuity and hierarchy are separate but equally important issues of homology.

Chao-I Chen et al. (2004) West Coast Worm Meeting "A Bayesian approach toward analyzing the network of genes involved in C. elegans programmed cell death"

Chao-I Chen, Vebjorn Ljosa, S Rao Jammalamadaka, Chiou-Wei Tsai, Ambuj K Singh, Thomas A McCloskey, Xiaofang Lei, Joel H Rothman

[West Coast Worm Meeting, 2004]

From an RNAi screen for genes that repress apoptosis, we have identified a set of about 130 candidates (see abstract by McCloskey et al.). We are using computational methods in an effort to predict functional networks through which these genes may act and to identify additional candidates and their relationships within the postulated networks. We are initially working with a number of datasets as the basis for our predictions: microarray expression data, the physical orientation of genes within the worm genome, phylogenetic profile data, and PSORT predictions of protein localization. The datasets are normalized according to their overlap with the worm interactome and Wormbase subcellular localization data. They are then combined using a nave Bayesian network, to yield a set of potential functionally interacting protein pairs along with a likelihood score for each pair. Finally, we construct network maps of the protein pairs that fall above a desired likelihood ratio. Our initial efforts suggest a cluster of functional interactions that are predicted from the gene set identified by the RNAi screen; refinements of the computational methods are in progress.