Campbell, Richard et al. (2015) International Worm Meeting "UNC-62 alternative transcripts differentially regulate UNC-55 expression and neural differentiation of GABAergic VD motor neurons."

Campbell, Richard, Walthall, Walter W.

[International Worm Meeting, 2015]

The animal's sinuous locomotion is a direct result of a cross activational/inhibitory network of motor neurons in the ventral nerve cord (VNC). This is network is composed of cholinergic (excitatory) inputs and GABAergic (inhibitory) inputs that originate from distinct classes and subclasses of motor neurons. The excitatory motor neurons are comprised of the A (for backward locomotion) and B(for forward locomotion). The inhibitory motor neurons are comprised of the D class motor neurons which are predicted to be required for both backward and forward locomotion. Both cholinergic and GABAergic classes can be further subdivided by innervation type and developmental origin. The GABAergic DD subclass is embryonic and innervates dorsal muscle in adult animals while the VD subclass is postembryonic and innervates ventral muscle. Both the DD and VD motor neurons express the transcription factor, UNC-30 which is necessary and sufficient for post mitotic differentiation GABAergic D class motor neurons. The VD motor neurons express a nuclear hormone receptor, UNC-55 which prevents the VD motor neurons from innervating the dorsal muscle and assuming a DD like fate through the suppression of various UNC-30 transcriptional targets. Interestingly, UNC-55 is not transcriptionally regulated by UNC-30. Thus in the DD and VD motor neurons which share very similar developmental mechanisms, how is the expression of UNC-55 regulated in the VNC?To address this question, the transcriptional activation of unc-55 and the differentiation of the VD motor neurons was tested utilizing bioinformatics, mutant analyses of candidate regulators, promoter dissection, exon specific disruption utilizing CRISPR/Cas9 and GFP constructs. Several putative transcription factor binding sites (cis sites) corresponding to the MEIS domain transcription factor, UNC-62 were found on the unc-55 promoter. Different mutant alleles of UNC-62 were found to repress, activate or have no effect on punc-55::gfp expression. Interestingly, each mutant allele of UNC-62 disrupts alternatively spliced or transcribed exons. Dissection of the unc-55 promoter identified multiple regions and putative cis sites that correlate with the UNC-62 mutant expression patterns. These data provide evidence that different isoforms of UNC-62 are required for activation and repression of unc-55 transcription and subsequently VD motor neuron differentiation. Isoform specific transcriptional regulation of differentiating neurons is a relatively unexplored area of research and represents an interesting mechanism for differentiation in neuronal subtypes.

Campbell, Richard et al. (2017) International Worm Meeting "Quantitative genetic mapping of difference in oxygen and carbon dioxide-evoked behaviors that are dependent on environmental growth conditions."

Lowder, Mark, McGrath, Patrick, Campbell, Richard

[International Worm Meeting, 2017]

The basis of behavioral variation in populations of animals is rooted in genetic, environmental and neuronal diversity. Since C. elegans is amenable to controlling each of these factors, we are seeking to understand how environmental and genetic diversity gives rise to natural differences in behaviors. Wild isolate strains such as the Hawaiian strain, CB4856, are very sensitive to small changes in atmospheric O2 and CO2 and exhibit a robust increase in turning and increase in speed in response to a shift from 20% O2/1% CO2 to 21% O2/0% CO2. Interestingly, this behavior is dependent on environmental growth conditions. If animals are grown on uniform lawns lacking an O2 gradient this response disappears. We asked if these O2 and CO2 responses are similar across different wild isolates. We found that there was variation among a representative panel of 12 wild isolates with some strains showing robust responses and some showing little to no change. To understand the genetic basis for this variation in O2 and CO2 behaviors, we are taking two approaches. First, we will perform QTL mapping on recombinant inbred lines we generated between MY14 (which does not show the sharp change in speed and turning behavior) and a modified N2 strain that contains the ancestral alleles of npr-1 and glb-5 (which shows the sharp change and speed and turning behavior. We will also perform GWAS on a large panel of wild isolates collected and sequenced by the CeNDR resource. We anticipate finding causal variants in other loci that are responsible for growth-dependent O2 and CO2 behaviors.

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

Zhao, Yuehui et al. (2017) International Worm Meeting "Quantitative fitness analysis of two laboratory strains of C. elegans."

McGrath, Patrick, Campbell, Richard, Zhao, Yuehui

[International Worm Meeting, 2017]

Many biological traits have a significant but complex genetic basis. Identification of causal genetic variants leads to a better understanding regarding the mechanisms of biological trait differences. As a model for complex traits, we are studying an unintentional metazoan experimental evolution experiment performed in C. elegans. Two laboratory domesticated C. elegans strains, N2 and LSJ2, share a common ancestor following its isolation from the wild in 1951. The N2 strain was cultured on agar plates seeded with bacteria for ~11 years while the LSJ2 was cultured in axenic liquid media ~50 years. We have previously found that mutations in npr-1 and glb-5 were fixed in the N2 strain, resulting in the suppression of aggregation and bordering behavior to avoid high O2 levels on agar plate. Using a digital PCR-based competition assay, we quantify the relative fitness effects of npr-1 and glb-5 ancestry/derived alleles. We find epistatic interaction between these two derived alleles: while the npr-1 derived allele shows fitness advantages in agar plate conditions regardless of genetic background, the glb-5 derived allele enhances the npr-1 fitness effect only in the derived npr-1 background. Unexpectedly, the fitness benefits of these two alleles seems to occur independently of their effects on behavior as the N2 strain showed increased fitness at 3% and 10% O2 levels where aggregation and bordering is suppressed. To systematically study the potential G x G and G x E in these two strains, we performed fitness QTL mapping using inbred lines (RILs) from N2*(npr-1 glb-5 ancestry alleles) x LSJ2 on agar plates under two culture conditions: non-starving and starving. We found one QTL with a strong effect on fitness centered over the chromatin remodeling factor nurf-1. Additionally, we found two QTLs showing a GxE interaction effect. Interestingly, despite lacking the derived alleles of npr-1 or glb-5, we found one of the RILs had a high relative fitness equal to the N2 strain. This RIL strain showed changes to bordering and aggregation behaviors distinguishable from the N2 strain. The potential explanations for this high fitness outlier could be due to the fixation of a de novo mutation or higher ordered epistasis of specific combinations of N2 and LSJ2 alleles. We will report the result of our mapping experiments to distinguish between these two possibilities. This study implies experimental evolution approach could be a good method to understand metazoan complex traits and evolution.

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.

Consortium Wormbase et al. (2000) West Coast Worm Meeting "From ACeDB to a more complete and usable database"

Consortium Wormbase, Foltz NL, Schwarz EM, Sternberg PW

[West Coast Worm Meeting, 2000]

We briefly describe the current status and plans for WormBase, initially an extension of the existing ACeDB database with a new user interface. The WormBase consortium includes the team that developed ACeDB (Richard Durbin and colleagues at the Sanger Centre; Jean Thierry-Mieg and colleagues at Montpellier); Lincoln Stein and colleagues at Cold Spring Harbor, who developed the current web interface for WormBase; and John Spieth and colleagues at the Genome Sequencing Center at Washington University, who along with the Sanger Centre team, continue to annotate the genomic sequence. The Caltech group will curate new data including cell function in development, behavior and physiology, gene expression at a cellular level, and gene interactions. Data will be extracted from the literature, as well as by community submission. We look forward to providing the C. elegans and broader research community easy access to vast quantities of high quality data on C. elegans. Also, we welcome your suggestions and criticism at any time. WormBase can be accessed at www.wormbase.org.