[
International Worm Meeting,
2015]
Many tissue-specific interventions have been shown to effect organismal aging in a cell non-autonomous manner. How aging is coordinated between multiple cells and tissues is still poorly understood. The intestine not only acts as site of food digestion and energy storage, but is also a major endocrine tissue in the worm. Several studies have indicated that the intestine is important for the regulation of systemic aging and key aging pathways are known to act either in the intestine or signal towards it.We identified a transporter protein that displays homology to a large family of evolutionarily conserved solute carriers (SLCs). SLCs have been shown to transport a wide variety of substances such as nutrients, hormones and drugs across cell membranes. Interestingly, we found that the cellular context is important in the regulation of aging: Intestine-specific knock-down of this transporter is sufficient to extend the lifespan of C. elegans, while RNAi in a wild-type background has no effect on longevity. We show that this transporter modulates the activity of several genes involved in fat metabolism and knock-down via RNAi reduces fat accumulation. We further show that the lifespan extending effect is independent of the FOXO transcription factor DAF-16. Surprisingly, we found that this transporter is required for the long-life of germline-less animals and knock-down of this gene prevents the activation of several key transcription factors. However, the activity of this transporter is not generally required for long life, since knocking down this gene does not shorten the long life of other longevity mutants.Current and future analysis will focus on the genetic requirements and aim to decipher the molecular mechanism of the different lifespan modulating effects of this transporter. In addition metabolomics analysis will aid to identify potential target molecules and help to widen our understanding of the role of metabolism in aging. More generally, these results demonstrate the importance of the cellular context for the physiological function of factors involved in the regulation of aging. .
Burton RA, Tanner NA, Alhassan A, Guelig D, Poole CB, Carlow CK, Zhang Y, LaBarre P, Wanji S, Li Z, Diesburg S, Evans TC
[
PLoS One,
2017]
Accurate detection of filarial parasites in humans is essential for the implementation and evaluation of mass drug administration programs to control onchocerciasis and lymphatic filariasis. Determining the infection levels in vector populations is also important for assessing transmission, deciding when drug treatments may be terminated and for monitoring recrudescence. Immunological methods to detect infection in humans are available, however, cross-reactivity issues have been reported. Nucleic acid-based molecular assays offer high levels of specificity and sensitivity, and can be used to detect infection in both humans and vectors. In this study we developed loop-mediated isothermal amplification (LAMP) tests to detect three different filarial DNAs in human and insect samples using pH sensitive dyes for enhanced visual detection of amplification. Furthermore, reactions were performed in a portable, non-instrumented nucleic acid amplification (NINA) device that provides a stable heat source for LAMP. The efficacy of several strand displacing DNA polymerases were evaluated in combination with neutral red or phenol red dyes. Colorimetric NINA-LAMP assays targeting Brugia Hha I repeat, Onchocerca volvulus GST1a and Wuchereria bancrofti LDR each exhibit species-specificity and are also highly sensitive, detecting DNA equivalent to 1/10-1/5000th of one microfilaria. Reaction times varied depending on whether a single copy gene (70 minutes, O. volvulus) or repetitive DNA (40 min, B. malayi and W. bancrofti) was employed as a biomarker. The NINA heater can be used to detect multiple infections simultaneously. The accuracy, simplicity and versatility of the technology suggests that colorimetric NINA-LAMP assays are ideally suited for monitoring the success of filariasis control programs.