Jeong DE et al. (2018) Methods Mol Biol "Western Blot Analysis of C. elegans Proteins."

Lee SV, Jeong DE, Lee Y

[Methods Mol Biol, 2018]

C. elegans has been widely used as a model organism for basic biological research and is particularly amenable for molecular genetic studies using a broad repertoire of techniques. Biochemical approaches, including Western blot analysis, have emerged as a powerful tool in C. elegans biology for understanding molecular mechanisms that link genotypes to phenotypes. Here, we provide a protocol for Western blot analysis using protein extracts obtained from C. elegans samples.

Jeong DE et al. (2012) Front Genet "Regulation of lifespan by chemosensory and thermosensory systems: findings in invertebrates and their implications in mammalian aging."

Artan M, Lee SJ, Jeong DE, Seo K

[Front Genet, 2012]

Many environmental factors that dynamically change in nature influence various aspects of animal physiology. Animals are equipped with sensory neuronal systems that help them properly sense and respond to environmental factors. Several studies have shown that chemosensory and thermosensory neurons affect the lifespan of invertebrate model animals, including Caenorhabditis elegans and Drosophila melanogaster. Although the mechanisms by which these sensory systems modulate lifespan are incompletely understood, hormonal signaling pathways have been implicated in sensory system-mediated lifespan regulation. In this review, we describe findings regarding how sensory nervous system components elicit physiological changes to regulate lifespan in invertebrate models, and discuss their implications in mammalian aging.

Jeong DE et al. (2017) EMBO J "Mitochondrial chaperone HSP-60 regulates anti-bacterial immunity via p38 MAP kinase signaling."

Artan M, Ha CM, Lee D, Jeong DE, Seo M, Lee JE, Lee Y, Lee SV, Hwang AB, Ryu Y, Seo K, Yoo JY, Jo JH, Oh YM, Kim HJ, Baek H, Son HG, Hwang SY, Hwang W

[EMBO J, 2017]

Mitochondria play key roles in cellular immunity. How mitochondria contribute to organismal immunity remains poorly understood. Here, we show that HSP-60/HSPD1, a major mitochondrial chaperone, boosts anti-bacterial immunity through the up-regulation of p38 MAP kinase signaling. We first identify 16 evolutionarily conserved mitochondrial components that affect the immunity of Caenorhabditis elegans against pathogenic Pseudomonas aeruginosa (PA14). Among them, the mitochondrial chaperone HSP-60 is necessary and sufficient to increase resistance to PA14. We show that HSP-60 in the intestine and neurons is crucial for the resistance to PA14. We then find that p38 MAP kinase signaling, an evolutionarily conserved anti-bacterial immune pathway, is down-regulated by genetic inhibition of hsp-60, and up-regulated by increased expression of hsp-60 Overexpression of HSPD1, the mammalian ortholog of hsp-60, increases p38 MAP kinase activity in human cells, suggesting an evolutionarily conserved mechanism. Further, cytosol-localized HSP-60 physically binds and stabilizes SEK-1/MAP kinase kinase 3, which in turn up-regulates p38 MAP kinase and increases immunity. Our study suggests that mitochondrial chaperones protect host eukaryotes from pathogenic bacteria by up-regulating cytosolic p38 MAPK signaling.

Jeong DE et al. (2020) PLoS Genet "Inhibition of the oligosaccharyl transferase in Caenorhabditis elegans that compromises ER proteostasis suppresses p38-dependent protection against pathogenic bacteria."

Yoo JY, Ham S, Kwon S, Roh TY, Lee D, Jeong DE, Lee Y, Lee SV, Hwang SY, Park HH

[PLoS Genet, 2020]

The oligosaccharyl transferase (OST) protein complex mediates the N-linked glycosylation of substrate proteins in the endoplasmic reticulum (ER), which regulates stability, activity, and localization of its substrates. Although many OST substrate proteins have been identified, the physiological role of the OST complex remains incompletely understood. Here we show that the OST complex in C. elegans is crucial for ER protein homeostasis and defense against infection with pathogenic bacteria Pseudomonas aeruginosa (PA14), via immune-regulatory PMK-1/p38 MAP kinase. We found that genetic inhibition of the OST complex impaired protein processing in the ER, which in turn up-regulated ER unfolded protein response (UPRER). We identified vitellogenin VIT-6 as an OST-dependent glycosylated protein, critical for maintaining survival on PA14. We also showed that the OST complex was required for up-regulation of PMK-1 signaling upon infection with PA14. Our study demonstrates that an evolutionarily conserved OST complex, crucial for ER homeostasis, regulates host defense mechanisms against pathogenic bacteria.

Perez-Escudero A et al. (2007) Proc Natl Acad Sci U S A "Optimally wired subnetwork determines neuroanatomy of Caenorhabditis elegans."

de Polavieja GG, Perez-Escudero A

[Proc Natl Acad Sci U S A, 2007]

Wiring cost minimization has successfully explained many structures of nervous systems. However, in the nematode Caenorhabditis elegans, for which anatomical data are most detailed, wiring economy is thought to play only a partial role and alone has failed to account for the grouping of neurons into ganglia [Chen BL, Hall DH, Chklovskii DB (2006) Proc Natl Acad Sci USA 103:4723-4728; Kaiser M, Hilgetag CC (2006) PLoS Comput Biol 2:e95; Ahn Y-Y, Jeong H, Kim BJ (2006) Physica A 367:531-537]. Here, we test the hypothesis that optimally wired subnetworks can exist within nonoptimal networks, thus allowing wiring economy to give an improved prediction of spatial structure. We show in C. elegans that the small subnetwork of wires connecting sensory and motor neurons with sensors and muscles, comprising only 15% of connections, is close to optimal and alone predicts the main features of the spatial segregation of neurons into ganglia and encephalization. Moreover, a method to dissect networks into optimal and nonoptimal components is shown to find a large near-optimal subnetwork of 84% of neurons with a very low position error of 5.4%, and that explains clustering of neurons into ganglia and encephalization to fine detail. In general, we expect realistic networks not to be globally optimal in wire cost. We thus propose the strategy of using near-optimal subnetworks to understand neuroanatomical structure.