Servello FA et al. (2022) Elife "Neuronal temperature perception induces specific defenses that enable C. elegans to cope with the enhanced reactivity of hydrogen peroxide at high temperature."

Sengupta P, Apfeld J, Servello FA, Martin OMF, Oswal N, Derosiers N, Lindberg A, Fernandes R, Harris N, Eder M, Stroustrup N

[Elife, 2022]

Hydrogen peroxide is the most common reactive chemical that organisms face on the microbial battlefield. The rate with which hydrogen peroxide damages biomolecules required for life increases with temperature, yet little is known about how organisms cope with this temperature-dependent threat. Here, we show that Caenorhabditis elegans nematodes use temperature information perceived by sensory neurons to cope with the temperature-dependent threat of hydrogen peroxide produced by the pathogenic bacterium Enterococcus faecium. These nematodes preemptively induce the expression of specific hydrogen peroxide defenses in response to perception of high temperature by a pair of sensory neurons. These neurons communicate temperature information to target tissues expressing those defenses via an insulin/IGF1 hormone. This is the first example of a multicellular organism inducing their defenses to a chemical when they sense an inherent enhancer of the reactivity of that chemical.

Strome S et al. (2014) Cold Spring Harb Perspect Biol "Regulation of the X chromosomes in Caenorhabditis elegans."

Strome S, Kelly WG, Ercan S, Lieb JD

[Cold Spring Harb Perspect Biol, 2014]

Dosage compensation, which regulates the expression of genes residing on the sex chromosomes, has provided valuable insights into chromatin-based mechanisms of gene regulation. The nematode Caenorhabditis elegans has adopted various strategies to down-regulate and even nearly silence the X chromosomes. This article discusses the different chromatin-based strategies used in somatic tissues and in the germline to modulate gene expression from the C. elegans X chromosomes and compares these strategies to those used by other organisms to cope with similar X-chromosome dosage differences.

Chang HW et al. (2015) Free Radic Biol Med "Collaboration between mitochondria and the nucleus is key to long life in Caenorhabditis elegans."

Shtessel L, Sylvia Lee S, Chang HW

[Free Radic Biol Med, 2015]

Recent findings in diverse organisms strongly support a conserved role for mitochondrial electron transport chain dysfunction in longevity modulation, but the underlying mechanisms are not well understood. One way cells cope with mitochondrial dysfunction is through a retrograde transcriptional reprogramming response. In this review, we primarily focus on the work that has been performed in Caenorhabditis elegans to elucidate these mechanisms. We describe several transcription factors that participate in mitochondria-to-nucleus signaling and discuss how they mediate the relationship between mitochondrial dysfunction and life span.

Nikonorova, Inna et al. (2021) International Worm Meeting "Deciphering the ciliary extracellular vesicle (EV) proteome"

Nikonorova, Inna, Cope, Alexander, Barr, Maureen, Power, Kaiden, Walsh, Jonathon, Wang, Juan, Shah, Premal, Akella, Jyothi

[International Worm Meeting, 2021]

Extracellular vesicles (EVs) are emerging as a universal means of cell-to-cell communication and hold great potential in diagnostics and regenerative therapies. However, the EV field lacks a fundamental understanding of biogenesis, cargo content, signaling, and target interactions. EVs that are transmitted by cilia represent a particular challenge due to small volume of the organelle. Here, we used our established C. elegans system to determine the composition and explore the function of ciliary EVs. We took advantage of the fact that C. elegans releases ciliary EVs from 21 male-specific neurons and 6 core IL2 neurons into environment and thus provides a great platform for discovery of evolutionarily conserved ciliary EV cargo. To collect ciliary EVs we developed a biochemical enrichment procedure based on buoyant density centrifugation and high-resolution fractionation. Using fluorescent-tagged EV cargo PKD-2::GFP and superresolution microscopy we tracked ciliary EVs in the collected fractions and identified two populations of PKD-2 carrying EVs that differ in their densities. Proteomic analysis of the PKD-2 EV-enriched fractions revealed 2,888 proteins of C. elegans EVome that likely originate from multiple tissues. Top candidates were validated via generation of transgenic or CRISPR reporters and visualization of EV release using super-resolution microscopy. This strategy revealed that the male reproductive system is a major source of non-ciliary EVs. To extract ciliary EV cargoes, we integrated our dataset with published transcriptomic data. We identified new ciliary EV cargo involved in nucleotide binding and RNA interference, suggesting that environmentally-released ciliary EVs may also carry nucleic acids. Our work serves as a springboard for discoveries in the EV field and will help shed light on the contribution of ciliary EVs to the pathophysiology of abnormal EV signaling, including ciliopathies, cancer, and neurodegenerative diseases.

Sardaraz M et al. (2016) J Bioinform Comput Biol "Advances in high throughput DNA sequence data compression."

Ikram AA, Sardaraz M, Tahir M

[J Bioinform Comput Biol, 2016]

Advances in high throughput sequencing technologies and reduction in cost of sequencing have led to exponential growth in high throughput DNA sequence data. This growth has posed challenges such as storage, retrieval, and transmission of sequencing data. Data compression is used to cope with these challenges. Various methods have been developed to compress genomic and sequencing data. In this article, we present a comprehensive review of compression methods for genome and reads compression. Algorithms are categorized as referential or reference free. Experimental results and comparative analysis of various methods for data compression are presented. Finally, key challenges and research directions in DNA sequence data compression are highlighted.

Nishida, Y. et al. (2013) International Worm Meeting "Design of the microchip device to dissect the neural circuit based on thermotactic behavior in C. elegans."

Kobayashi, K., Jaehoon, J., Nakajima, M., Takeuchi, M., Fukuda, T., Mori, I., Nishida, Y.

[International Worm Meeting, 2013]

Animals cope with environmental stimuli by altering behaviors. Previous studies have characterized the thermotactic neural circuit, in which temperature is sensed and processed through the coordination of thermosensory neurons AFD and AWC, and interneurons AIY, AIZ and RIA in C. elegans (Mori et. al., 2007). This simple circuit is profitable to dissect neural activities of the respective neurons in response to temperature stimuli. However, it is unknown how the activities mediate the behavior to cope with environmental temperature. The recent study shows that RIA interneurons, which receive sensory inputs, encode head movement (Hendricks et. al., 2012). This finding provides a clue to tie the neural activities to not only the thermosensory inputs but also the behavioral outputs.In this study, we aim to study how the thermotactic neural circuit processes the temperature and mediates the behavior by monitoring the neural activities of the respective neurons for thermotactic behavior. We are now designing the microchip device to control both temperature stimuli and head movements. First, we are optimizing the shape of microfluidic channel for stable fixation of the animals' body to ensure free head movements. We are planning to fabricate a device for handling head movements by manipulation of a micro-probe attached to head region of the animals. We are also fabricating temperature control system to present the animals with accurate temperature stimuli in the microchip device. Our study surely supports understanding how temperature is sensed and processed through the neural circuit to mediate thermotactic behavior.

Sugi T et al. (2011) Nat Neurosci "Regulation of behavioral plasticity by systemic temperature signaling in Caenorhabditis elegans."

Nishida Y, Sugi T, Mori I

[Nat Neurosci, 2011]

Animals cope with environmental changes by altering behavioral strategy. Environmental information is generally received by sensory neurons in the neural circuit that generates behavior. However, although environmental temperature inevitably influences an animal's entire body, the mechanism of systemic temperature perception remains largely unknown. We show here that systemic temperature signaling induces a change in a memory-based behavior in C. elegans. During behavioral conditioning, non-neuronal cells as well as neuronal cells respond to cultivation temperature through a heat-shock transcription factor that drives newly identified gene expression dynamics. This systemic temperature signaling regulates thermosensory neurons non-cell-autonomously through the estrogen signaling pathway, producing thermotactic behavior. We provide a link between systemic environmental recognition and behavioral plasticity in the nervous system.

Shigyou K et al. (2021) J Vis Exp "Calcium Imaging in Freely Behaving Caenorhabditis elegans with Well-Controlled, Nonlocalized Vibration"

Sugi T, Shigyou K, Igarashi R, Maeoka H

[J Vis Exp, 2021]

Nonlocalized mechanical forces, such as vibrations and acoustic waves, influence a wide variety of biological processes from development to homeostasis. Animals cope with these stimuli by modifying their behavior. Understanding the mechanisms underlying such behavioral modification requires quantification of neural activity during the behavior of interest. Here, we report a method for calcium imaging in freely behaving Caenorhabditis elegans with nonlocalized vibration of specific frequency, displacement, and duration. This method allows the production of well-controlled, nonlocalized vibration using an acoustic transducer and quantification of evoked calcium responses at single-cell resolution. As a proof of principle, the calcium response of a single interneuron, AVA, during the escape response of C. elegans to vibration is demonstrated. This system will facilitate understanding of neural mechanisms underlying behavioral responses to mechanical stimuli.

Tomioka, M. et al. (2017) International Worm Meeting "A versatile insulin-like signaling regulates taste avoidance learning."

Tomioka, M., Iino, Y.

[International Worm Meeting, 2017]

During life, animals experience a myriad of life-threatening events and cope with them by physiological and behavioral responses. We have found that an alternative splicing (AS) event in the insulin receptor gene, daf-2, has strong impacts on several biological processes such as development, lifespan and behavior in C. elegans. DAF-2a, which is produced by skipping of a cassette exon mainly resides in the cell body to control transcription of genes related to morphogenesis and stress responses, whereas a cassette exon-inclusion isoform, DAF-2c, is translocated to neuronal axons and regulates learning of the salt concentrations experienced under starvation, which we call taste avoidance learning. This AS event appears to balance physiological and behavioral responses to cope with a variety of life-threatening conditions. Among 40 insulin-like peptides in C. elegans, an insulin-like peptide, INS-1, plays an important role in taste avoidance learning. Mutants of INS-1 show a marked defect in taste avoidance learning. INS-1 is secreted from sensory neurons and interneurons that have synaptic inputs to the gustatory neuron ASER and acts on the axonal DAF-2 isoform, DAF-2c, in ASER in the learning. We demonstrated that the INS-1-to-DAF-2c signal during salt chemotaxis, but not during starvation conditioning, is required for starvation-induced salt avoidance. On the other hand, the cell body isoform DAF-2a may control learning during salt conditioning through the FOXO transcription factor DAF-16. Our study proposes a model in which the versatile insulin-like signaling acting at different subcellular sites regulates taste avoidance learning in C. elegans.

Dorati F et al. (2018) Microorganisms "Coping with Environmental Eukaryotes; Identification of Pseudomonas syringae Genes during the Interaction with Alternative Hosts or Predators."

Jackson RW, Shaw LJ, Dorati F, Barrett GA, Arnold DL, Waterfield NR, Caballero P, Arseneault T, Murillo J, Studholme DJ, Sanchez-Contreras M, Jose MS

[Microorganisms, 2018]

Understanding the molecular mechanisms underpinning the ecological success of plant pathogens is critical to develop strategies for controlling diseases and protecting crops. Recent observations have shown that plant pathogenic bacteria, particularly <i>Pseudomonas</i>, exist in a range of natural environments away from their natural plant host e.g., water courses, soil, non-host plants. This exposes them to a variety of eukaryotic predators such as nematodes, insects and amoebae present in the environment. Nematodes and amoeba in particular are bacterial predators while insect herbivores may act as indirect predators, ingesting bacteria on plant tissue. We therefore postulated that bacteria are probably under selective pressure to avoid or survive predation and have therefore developed appropriate coping mechanisms. We tested the hypothesis that plant pathogenic <i>Pseudomonas syringae</i> are able to cope with predation pressure and found that three pathovars show weak, but significant resistance or toxicity. To identify the gene systems that contribute to resistance or toxicity we applied a heterologous screening technique, called Rapid Virulence Annotation (RVA), for anti-predation and toxicity mechanisms. Three cosmid libraries for <i>P. syringae</i> pv. <i>aesculi</i>, pv. <i>tomato</i> and pv. <i>phaseolicola</i>, of approximately 2000 cosmids each, were screened in the susceptible/non-toxic bacterium <i>Escherichia coli</i> against nematode, amoebae and an insect. A number of potential conserved and unique genes were identified which included genes encoding haemolysins, biofilm formation, motility and adhesion. These data provide the first multi-pathovar comparative insight to how plant pathogens cope with different predation pressures and infection of an insect gut and provide a foundation for further study into the function of selected genes and their role in ecological success.