Skrdla PJ (2005) Biophys Chem "Statistical kinetic approach for modeling lifespan."

Skrdla PJ

[Biophys Chem, 2005]

Lifespan regulation through gene expression involves complex biochemical processes. Unfortunately, current mathematical models for treating lifespan data afford little insight into the mechanisms that control longevity. In this work, we demonstrate the use of a novel kinetic model to successfully fit the lifespan curves of the nematode, Caenorhabditis elegans. Our findings show that population aging may be treated analogously to a dispersive chemical process [P.J. Skrdla, R.T. Robertson., J. Phys. Chem. B 109 10611 (2005)]. Much like the Gompertz model, only two fit parameters, alpha and beta, are needed to adequately describe the entire data set for each nematode population. These parameters relate a ''global first-order time constant'' and a ''global second-order rate constant'', with units of (time) and (time)(-2), respectively. In C. elegans, the increased longevity resulting from DAF-16 (a transcription factor) activity in the intestinal tissue correlates with a larger alpha value and a smaller beta value; the opposite is true for animals with shorter lifespans. A basic physical interpretation of the two parameters is provided.

Morton DB et al. (1999) Curr Biol "Soluble guanylyl cyclases in Caenorhabditis elegans: NO is not the answer."

Hudson ML, O'Shea M, Waters E, Morton DB

[Curr Biol, 1999]

Guanylyl cyclases (GCs), the enzymes that synthesize cyclic GMP (cGMP), have classically been divided into two groups: receptor GCs and soluble GCs. Receptor GCs are integral membrane proteins such as the retinal guanylyl cyclases and the atrial natriuretic peptide receptors. Soluble GCs are heterodimeric proteins consisting of an alpha and a beta subunit that bind a heme group and are activated by nitric oxide (NO). The recent publication of the Caenorhabditis elegans genomic sequence has revealed an unexpected abundance of GCs.

Petcherski AG et al. (2000) Curr Biol "Mastermind is a putative activator for Notch."

Kimble J, Petcherski AG

[Curr Biol, 2000]

During signaling by the Notch receptor, Notch's intracellular domain is cleaved, moves to the nucleus and associates with a DNA-binding protein of the CSL class (CSL for CBF1, Suppressor of Hairless (Su(H)), LAG-1); as a result, target genes are transcriptionally activated (reviewed in [1,2]). In Caenorhabditis elegans, a glutamine-rich protein called LAG-3 forms a ternary complex with the Notch intracellular domain and LAG-1 and appears to serve as a transcriptional activator that is critical for signaling [3]. Although database searches failed to identify a LAG-3-related protein, we surmised that Notch signaling in other organisms might involve an analogous activity.

Noguez JH et al. (2012) ACS Chem Biol "A novel ascaroside controls the parasitic life cycle of the entomopathogenic nematode Heterorhabditis bacteriophora."

Ragains J, Ciche T, Butcher RA, Conner ES, Zhou Y, Noguez JH

[ACS Chem Biol, 2012]

Entomopathogenic nematodes survive in the soil as stress-resistant infective juveniles that seek out and infect insect hosts. Upon sensing internal host cues, the infective juveniles regurgitate bacterial pathogens from their gut that ultimately kill the host. Inside the host, the nematode develops into a reproductive adult and multiplies until unknown cues trigger the accumulation of infective juveniles. Here, we show that the entomopathogenic nematode Heterorhabditis bacteriophora uses a small-molecule pheromone to control infective juvenile development. The pheromone is structurally related to the dauer pheromone ascarosides that the free-living nematode Caenorhabditis elegans uses to control its development. However, none of the C. elegans ascarosides are effective in H. bacteriophora, suggesting that there is a high degree of species specificity. Our report is the first to show that ascarosides are important regulators of development in a parasitic nematode species. An understanding of chemical signaling in parasitic nematodes may enable the development of chemical tools to control these species.

Singh D et al. (2016) Genesis "Acute heat shock leads to cortical domain internalization and polarity loss in the C. elegans embryo."

Pohl C, Singh D, Odedra D, Lehmann C

[Genesis, 2016]

Many developmental processes are inherently robust due to network organization of the participating factors and functional redundancy. The heterogeneity of the factors involved and their connectivity puts these processes at risk of abrupt system collapse under stress. The polarization of the one-cell C. elegans embryo constitutes such an inherently robust process with functional redundancy. However, how polarization is affected by acute stress has not been thoroughly investigated. Here, we report that heat shock (34C, 1 h) triggers a highly reproducible loss of the anterior and collapse of the posterior polarity domains. Temperature-dependent loss of cortical non-muscle myosin II drastically reduces cortical tension and leads to internalization of large plasma membrane domains including the membrane-associated polarity factor PAR-2. After internalization, plasma membrane vesicles and associated factors cluster around centrosomes and are thereby withdrawn from the polarization process. Transient formation of the posterior polarity domain suggests that microtubule-induced self-organization of this domain is not compromised after heat shock. Hence, our data uncover that the polarization system undergoes a temperature-dependent collapse under acute stress. This article is protected by copyright. All rights reserved.