John Sulston, a pioneer in the developmental studies of the nematode <i>C. elegans</i> who went on to spearhead the sequencing of the genome of this organism and ultimately the human genome, died on 6th March 2018, shortly after being diagnosed with stomach cancer. Here, I reflect on John's life and work, with a particular focus on his time working on the developmental genetics and lineage of <i>C. elegans</i><i>.</i>
A slide taped to a window at the Woods Hole Marine Biology Laboratory was my first introduction to the touch receptor neurons of the nematode <i>Caenorhabditis elegans</i>. Studying these cells as a postdoc with Sydney Brenner gave me a chance to work with John Sulston on a fascinating set of neurons. I would never have guessed then that 43 years later I would still be excited about learning their secrets.
Cloning mua-3: some observations on the new Molecular Era John Plenefisch and Edward Hedgecock, Dept. of Biology, Johns Hopkins University, Baltimore MD 21218
John Sulston changed the way we do science, not once, but three times - initially with the complete cell lineage of the nematode <i>Caenorhabditis elegans</i>, next with completion of the genome sequences of the worm and human genomes and finally with his strong and active advocacy for open data sharing. His contributions were widely recognized and in 2002 he received the Nobel Prize in Physiology and Medicine.
Tc4 and Tc5: what makes them move and why it matters Christi Parham, Kristie Butze, Joanna Beinhorn and John Collins. Dept. of Biochemistry and Molecular Biology, University of New Hampshire. Durham, NH 03824
Sexual dimorphism is a device that supports genetic diversity while providing selective pressure against speciation. This phenomenon is at the core of sexually reproducing organisms. <i>Caenorhabditis elegans</i> provides a unique experimental system where males exist in a primarily hermaphroditic species. Early works of John Sulston, Robert Horvitz, and John White provided a complete map of the hermaphrodite nervous system, and recently the male nervous system was added. This addition completely realized the vision of <i>C. elegans</i> pioneer Sydney Brenner: a model organism with an entirely mapped nervous system. With this 'connectome' of information available, great strides have been made toward understanding concepts such as how a sex-shared nervous system (in hermaphrodites and males) can give rise to sex-specific functions, how neural plasticity plays a role in developing a dimorphic nervous system, and how a shared nervous system receives and processes external cues in a sexually-dimorphic manner to generate sex-specific behaviors. In <i>C. elegans</i>, the intricacies of male-mating behavior have been crucial for studying the function and circuitry of the male-specific nervous system and used as a model for studying human autosomal dominant polycystic kidney disease (ADPKD). With the emergence of CRISPR, a seemingly limitless tool for generating genomic mutations with pinpoint precision, the <i>C. elegans</i> model system will continue to be a useful instrument for pioneering research in the fields of behavior, reproductive biology, and neurogenetics.
Function of a Domain of the Myosin Heavy Chain Implicated in Familial Hypertrophic Cardiomyopathy Craig A. Almeida, Kerry E. Swift and John J. Collins Department of Biochemistry and Molecular, University of New Hampshire, Durham, NH 03820
<i>Caenorhabditis</i><i>elegans</i> is a valuable tool as an infection model toward the study of <i>Candida</i> species. In this work, we endeavored to develop a <i>C</i>. <i>elegans</i>-<i>Candida</i><i>parapsilosis</i> infection model by using the fungi as a food source. Three species of the C. parapsilosis complex (<i>C.</i><i>parapsilosis</i> (<i>sensu</i><i>stricto</i>), <i>Candida</i><i>orthopsilosis</i> and <i>Candida</i><i>metapsilosis</i>) caused infection resulting in <i>C. elegans</i> killing. All three strains that comprised the complex significantly diminished the nematode lifespan, indicating the virulence of the pathogens against the host. The infection process included invasion of the intestine and vulva which resulted in organ protrusion and hyphae formation. Importantly, hyphae formation at the vulva opening was not previously reported in <i>C</i>. <i>elegans</i>-<i>Candida</i> infections. Fungal infected worms in the liquid assay were susceptible to fluconazole and caspofungin and could be found to mount an immune response mediated through increased expression of <i>cnc</i>-<i>4</i>, <i>cnc</i>-<i>7</i>, and <i>fipr</i><i>-</i><i>22</i>/<i>23</i>. Overall, the <i>C</i>. <i>elegans</i>-<i>C</i>. <i>parapsilosis</i> infection model can be used to model <i>C</i>. <i>parapsilosis</i> host-pathogen interactions.
This review article highlights our efforts to decode the role of the nervous system in regulating intestinal lipid metabolism in <i>Caenorhabditis elegans</i>. Capitalizing on the prescient and pioneering work of Sydney Brenner and John Sulston in establishing <i>C. elegans</i> as an immensely valuable model system, we have uncovered critical roles for oxygen sensing, population density sensing and food sensing in orchestrating the balance between storing lipids and utilizing them for energy in the intestine, the major organ for lipid metabolism in this model system. Our long-term goal is to reveal the integrative mechanisms and regulatory logic that underlies the complex relationship between genes, environment and internal state in the regulation of energy and whole-body physiology.
Mutations causing a touch-insensitive phenotype in the nematode Caenorhabditis elegans have been the basis of studies on the specification of neuronal cell fate, inherited neurodegeneration, and the molecular nature of mechanosensory transduction. (C) 1993 John Wiley & sons, Inc.