Harold Smith (2006) WormBook "Sperm motility and MSP."

Harold Smith

[WormBook, 2006]

Form follows function, and this maxim is particularly true for the nematode sperm cell. Motility is essential for fertilization, and the process of spermatogenesis culminates in the production of a crawling spermatozoon with an extended pseudopod. However, the morphological similarity to amoeboid cells of other organisms is not conserved at the molecular level. Instead of utilizing the actin cytoskeleton and motor proteins, the pseudopod moves via the regulated assembly and disassembly of filaments composed of the major sperm protein (MSP). The current work reviews the structure and dynamics of MSP filament formation, the critical role of pH in MSP assembly, and the recent identification of components that regulate this process. The combination of cytological, biochemical, and genetic approaches in this relatively simple system make nematode sperm an attractive model for investigating the mechanics of amoeboid cell motility.

Smith ET et al. (1988) Business Week "Aging: Can it be slowed?"

Kelly KA, Smith ET, Brown CG

[Business Week, 1988]

Smith HE (2011) Biotechniques "Identifying insertion mutations by whole-genome sequencing."

Smith HE

[Biotechniques, 2011]

Insertion mutagenesis via mobile genetic element is a common technique for the analysis of gene function in model organisms. Next-generation sequencing offers an attractive approach for localizing the site of insertion, but alignment-based mapping of mobile genetic elements is challenging. A computational method for identifying insertion sites is reported herein. The technique was validated by mapping transposons in both bacterial and nematode species. The approach should be extensible to other systems that employ mobile genetic elements to generate mutations.

Smith SJ (1978) Nature "The structural gene for myosin: a close look."

Smith SJ

[Nature, 1978]

The humble soild nematode Caenorhabditis elegans has proved a useful tool for the extension of the study of gene-protein relationships from prokaryotic to eukaryotic organisms. A variety of uncoordinated (unc) mutants can be isolated by their behavioral characteristics, and electron micrographs show that such mutations are associated with disorganisation of muscle structure. One such mutant of the unc-54 gene (e675) has a normal amount of myosin but the number of thick filaments (myosin-containing...

Pliny A. Smith (2007) International Worm Meeting "Investigating C. elegans Aging in the classroom."

Pliny A. Smith

[International Worm Meeting, 2007]

C. elegans provides an attractive model for studying aging in an undergraduate classroom. Undergraduate students enrolled in a first year biological skills course, focused on aging, designed their own worm related longevity experiments. At the time the students submitted their proposals, they had sufficient background to make educated hypotheses and predictions of the experimental outcomes. Students selected from aging related worm strains, RNAi bacterial strains, and various chemical compounds/food sources in their experimental design, and then followed worm life spans to produce longevity curves. This data was then presented as a short research seminar after the conclusion of the experiments.

Smith RJ et al. (1988) Trop Med Parasitol "Vascular perfusion of Onchocerca volvulus nodules."

Williams JF, Smith RJ, Guderian RH, Cotter TP

[Trop Med Parasitol, 1988]

Perfusion of the vascular bed was achieved in 24 freshly excised nodules of Onchocerca volvulus varying from 0.5 to 2 cm in diameter. India Ink, Microfil polymer, or acrylate perfusates were passed through the vascular supply via cannulation of superficial capsular vessels. After clearing in glycerol or methyl salicylate, or KOH corrosion in the case of the acrylate, nodules were examined microscopically. Small nodules had an extensive blood supply, diffusely distributed throughout the nodule matrix, and in close association with the coils of the worms. In bigger nodules the central area appeared more dense, and intense vascularization appeared to be more peripheral; in the largest nodules the central core was not well vascularized, but a band of heavy vascularization was seen at the margin of the core, fed by superficial vessels and in close contact with worm coils. Very fine branches of the vascular tree were perfused by all three contrast media, but histologically there was evidence of incomplete filling of the smallest vessels. However, there was no extravasation of per-fusates around parasites, even where the approximation between between vessels and parasite surfaces was close. The possibility is considered that O. volvulus may control blood vessel proliferation by release of angiogenesis factors, analogous to rapidly growing solid tumors.

Smith, Heidi K. et al. (2012) Worm Breeder's Gazette "Cloning of che-6 and che-7"

Smith, Heidi K., Hobert, Oliver

[Worm Breeder's Gazette, 2012]

Smith-Vikos T et al. (2012) J Cell Sci "MicroRNAs and their roles in aging."

Smith-Vikos T, Slack FJ

[J Cell Sci, 2012]

MicroRNAs (miRNAs) are a class of short non-coding RNAs that bind mRNAs through partial base-pair complementarity with their target genes, resulting in post-transcriptional repression of gene expression. The role of miRNAs in controlling aging processes has been uncovered recently with the discovery of miRNAs that regulate lifespan in the nematode Caenorhabditis elegans through insulin and insulin-like growth factor-1 signaling and DNA damage checkpoint factors. Furthermore, numerous miRNAs are differentially expressed during aging in C. elegans, but the specific functions of many of these miRNAs are still unknown. Recently, various miRNAs have been identified that are up- or down-regulated during mammalian aging by comparing their tissue-specific expression in younger and older mice. In addition, many miRNAs have been implicated in governing senescence in a variety of human cell lines, and the precise functions of some of these miRNAs in regulating cellular senescence have helped to elucidate mechanisms underlying aging. In this Commentary, we review the various regulatory roles of miRNAs during aging processes. We highlight how certain miRNAs can regulate aging on the level of organism lifespan, tissue aging or cellular senescence. Finally, we discuss future approaches that might be used to investigate the mechanisms by which miRNAs govern aging processes.

Smith HE (2022) Methods Mol Biol "Mutation Mapping and Identification by Whole-Genome Sequencing."

Smith HE

[Methods Mol Biol, 2022]

Geneticists approach biology with a simple question: which genes are required for the pathway or process of interest? Classical genetic screens (aka forward genetics) in model organisms such as Caenorhabditis elegans have been the method of choice for answering that question. Next-generation sequencing provides the means to generate a comprehensive list of sequence variants, including the mutation of interest. Herein is described a workflow for sample preparation and data analysis to allow the simultaneous mapping and identification of candidate mutations by whole-genome sequencing in Caenorhabditis elegans.

Smith RL et al. (2012) Front Genet "Premature and accelerated aging: HIV or HAART?"

Brul S, Smith RL, Budovskaya Y, de Boer R, van der Spek H

[Front Genet, 2012]

Highly active antiretroviral therapy (HAART) has significantly increased life expectancy of the human immunodeficiency virus (HIV)-positive population. Nevertheless, the average lifespan of HIV-patients remains shorter compared to uninfected individuals. Immunosenescence, a current explanation for this difference invokes heavily on viral stimulus despite HAART efficiency in viral suppression. We propose here that the premature and accelerated aging of HIV-patients can also be caused by adverse effects of antiretroviral drugs, specifically those that affect the mitochondria. The nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral drug class for instance, is known to cause depletion of mitochondrial DNA via inhibition of the mitochondrial specific DNA polymerase-. Besides NRTIs, other antiretroviral drug classes such as protease inhibitors also cause severe mitochondrial damage by increasing oxidative stress and diminishing mitochondrial function. We also discuss important areas for future research and argue in favor of the use of Caenorhabditis elegans as a novel model system for studying these effects.