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.

Izquierdo EJ et al. (2016) Curr Opin Neurobiol "The whole worm: brain-body-environment models of C. elegans."

Izquierdo EJ, Beer RD

[Curr Opin Neurobiol, 2016]

Brain, body and environment are in continuous dynamical interaction, and it is becoming increasingly clear that an animal's behavior must be understood as a product not only of its nervous system, but also of the ongoing feedback of this neural activity through the biomechanics of its body and the ecology of its environment. Modeling has an essential integrative role to play in such an understanding. But successful whole-animal modeling requires an animal for which detailed behavioral, biomechanical and neural information is available and a modeling methodology which can gracefully cope with the constantly changing balance of known and unknown biological constraints. Here we review recent progress on both optogenetic techniques for imaging and manipulating neural activity and neuromechanical modeling in the nematode worm Caenorhabditis elegans. This work demonstrates both the feasibility and challenges of whole-animal modeling.

Fielenbach N et al. (2008) Genes Dev "C. elegans dauer formation and the molecular basis of plasticity."

Antebi A, Fielenbach N

[Genes Dev, 2008]

Because life is often unpredictable, dynamic, and complex, all animals have evolved remarkable abilities to cope with changes in their external environment and internal physiology. This regulatory plasticity leads to shifts in behavior and metabolism, as well as to changes in development, growth, and reproduction, which is thought to improve the chances of survival and reproductive success. In favorable environments, the nematode Caenorhabditis elegans develops rapidly to reproductive maturity, but in adverse environments, animals arrest at the dauer diapause, a long-lived stress resistant stage. A molecular and genetic analysis of dauer formation has revealed key insights into how sensory and dietary cues are coupled to conserved endocrine pathways, including insulin/IGF, TGF-beta, serotonergic, and steroid hormone signal transduction, which govern the choice between reproduction and survival. These and other pathways reveal a molecular basis for metazoan plasticity in response to extrinsic and intrinsic signals.

Ewbank JJ et al. (2011) Dis Model Mech "C. elegans: model host and tool for antimicrobial drug discovery."

Zugasti O, Ewbank JJ

[Dis Model Mech, 2011]

For almost four decades, the nematode Caenorhabditis elegans has been of great value in many fields of biological research. It is now used extensively in studies of microbial pathogenesis and innate immunity. The worm lacks an adaptive immune system and relies solely on its innate immune defences to cope with pathogen attack. Infectious microbes, many of which are of clinical interest, trigger specific mechanisms of innate immunity, and provoke the expression of antifungal or antibacterial polypeptides. In this review, we highlight some of these families of antimicrobial peptides (AMPs) and proteins that are candidates for the development of novel antibiotics. In addition, we describe how systems of C. elegans infection provide an increasing number of possibilities for large-scale in vivo screens for the discovery of new antimicrobial drugs. These systems open promising perspectives for innovative human therapies.

Bukhari H et al. (2019) Trends Cell Biol "Endogenous Fluorescence Tagging by CRISPR."

Bukhari H, Muller T

[Trends Cell Biol, 2019]

Fluorescent proteins have revolutionized biomedical research as they are easy to use for protein tagging, cope without fixation or permeabilization, and thus, enable live cell imaging in various models. Current methods allow easy and quick integration of fluorescent markers to endogenous genes of interest. In this review, we introduce the three central methods, zinc finger nucleases (ZFNs), transcription activator-like effectors (TALENs), and CRISPR, that have been widely used to manipulate cells or organisms. Focusing on CRISPR technology, we give an overview on homology-directed repair (HDR)-, microhomology-mediated end joining (MMEJ)-, and nonhomologous end joining (NHEJ)-based strategies for the knock-in of markers, figure out recent developments of the technique for highly efficient knock-in, and demonstrate pros and cons. We highlight the unique aspects of fluorescent protein knock-ins and pinpoint specific improvements and perspectives, like the combination of editing with stem cell derived organoid development.

Mori K (2009) J Biochem "Signalling pathways in the unfolded protein response: development from yeast to mammals."

Mori K

[J Biochem, 2009]

The accumulation of unfolded proteins in the endoplasmic reticulum (ER) under ER stress conditions activates a series of homoeostatic responses collectively termed the unfolded protein response (UPR). The UPR is unique in which the molecular mechanisms it uses to transmit signals from the ER lumen to the nucleus are completely different to those used for signalling from the plasma membrane. An ER stress signal is sensed and transmitted across the membrane by a transmembrane protein(s) in the ER. Interestingly, the number of such functional sensors/transducers, ubiquitously expressed, has increased with evolution, for example, one in Saccharomyces cerevisiae, two in Caenorhabditis elegans and Drosophila melanogaster, and three in mammals. Accordingly, mammalian cells are able to cope with ER stress in a more sophisticated manner. Here, I summarize the mechanisms and activation consequences of UPR signalling pathways in yeast, worm, fly and mammalian cells. I also discuss how they have evolved to counteract ER stress effectively.

Carranza-Garcia E et al. (2020) Front Cell Dev Biol "Insights Into the Hypometabolic Stage Caused by Prolonged Starvation in L4-Adult Caenorhabditis elegans Hermaphrodites."

Navarro RE, Carranza-Garcia E

[Front Cell Dev Biol, 2020]

Animals alter their reproductive cycles in response to changing nutritional conditions, to ensure that offspring production only occurs under favorable circumstances. These adaptive strategies include reversible hypometabolic states of dormancy such as &quot;arrest&quot; and &quot;diapause.&quot; The free-living nematode <i>Caenorhabditis elegans</i> can arrest its life cycle during some larval stages without modifying its anatomy and physiology until conditions improve but it can also modify its morphological and physiological features to cope with harsh conditions and transition into diapause. The well-defined &quot;dauer&quot; diapause was described more than 40 years ago and has been the subject of comprehensive investigations. The existence of another hypometabolic state, termed adult reproductive diapause (ARD), has been debated after it was first described 10 years ago. Here, we review the current knowledge regarding the effect of food deprivation during the pre-reproductive larval and adult stages on overall organismal homeostasis, highlighting the implications on germ cell maintenance and fertility preservation.

Maglioni S et al. (2016) Mitochondrion "C. elegans as a model organism for human mitochondrial associated disorders."

Maglioni S, Ventura N

[Mitochondrion, 2016]

Mitochondria are small cytoplasmic organelles whose most important function is to provide the energy required by our cells and organism to live. To maintain an adequate mitochondrial homeostasis cells possess numerous mitochondrial quality control and protective compensatory pathways, which can be activated to cope with a certain degree of mitochondrial dysfunction. However, when the mitochondrial damage is too severe and these defensive mechanisms are not anymore sufficient to deal with it, pathological signs arise. In the past few decades numerous genetic disorders ascribed to severe mitochondrial defects have been recognized with variable onset and symptomatology ranging from neuromuscular degeneration to cancer syndromes. Unfortunately, to date, only symptomatic and no curative therapies exist for most of these devastating, life-threating disorders. Model organisms, and especially the nematode Caenorhabditis elegans, with its sequenced and highly conserved genome, and a simple but well-characterized nervous system, have enormously contributed in the past years to gain insight into the pathogenesis and treatment of different diseases. Here, we will summarize some of the advantages offered by the nematode system to model neurodegenerative diseases associated with mitochondrial electron transport chain defects and screen for therapeutic interventions.

Maglioni S et al. (2016) Mech Ageing Dev "C. elegans screening strategies to identify pro-longevity interventions."

Ventura N, Maglioni S, Arsalan N

[Mech Ageing Dev, 2016]

Drugs screenings in search of enhancer or suppressors of selected readout(s) are nowadays mainly carried out in single cells systems. These approaches are however limited when searching for compounds with effects at the organismal level. To overcome this drawback the use of different model organisms to carry out modifier screening has exponentially grown in the past decade. Unique characteristics such as easy manageability, low cost, fast reproductive cycle, short lifespan, simple anatomy and genetic amenability, make the nematode Caenorhabditis elegans especially suitable for this purpose. Here we briefly review the different high-throughput and high-content screenings which exploited the nematode to identify new compounds extending healthy lifespan. In this context, we describe our recently developed screening strategy to search for pro-longevity interventions taking advantage of the very reproducible phenotypes observed in C. elegans upon different degrees of mitochondrial stress. Indeed, in Mitochondrial mutants, the processes induced to cope with mild mitochondrial alterations during development, and ultimately extending animal lifespan, lead to reduced size and induction of specific stress responses. Instead, upon strong mitochondrial dysfunction, worms arrest their development. Exploiting these automatically quantifiable phenotypic readouts, we developed a new screening approach using the Cellomics ArrayScanVTI-HCS Reader and identified a new pro-longevity drug.