CAENORHABDITIS ELEGANS

Caenorhabditis elegans has been proven to be a useful model organism for investigating molecular and cellular aspects of numerous human diseases. More recently, investigators have explored the use of this organism as a tool for drug discovery. Although earlier drug screens were labor-intensive and low in throughput, recent advances in high-throughput liquid workflows, imaging platforms and data analysis software have made C. elegans a viable option for automated high-throughput drug screens. In this sense, WMicrotracker system has become a very useful tool for worm researchers allowing to perform fast screenings and automated biological output readout.

Technology compatibility:

Anthelmintics

Anthelmintic is the term used to describe a drug used to treat infections of animals with parasitic worms. This includes both flat worms, e.g., flukes (trematodes) and tapeworms (cestodes) as well as round worms (nematodes). The parasites are of huge importance for human tropical medicine and for veterinary medicine.
Although C.elegans is a non parasitic free living animal, it can be used to perform investigations on anthelminthics and nematicides.

Chemical Screening 

• Practical High-Throughput Method to Screen Compounds for Anthelmintic Activity against Caenorhabditis elegans. Taki AC et al. Molecules 2021. “HitFinder” library (Maybridge). HTS 384w. ONE

• Caenorhabditis Elegans Infrared-Based Motility Assay Identified New Hits For Nematicide Drug Development. Risi G et al. Vet Sci 2019. Pathogen Box library. HTS. ONE

• Caenorhabditis elegans as a valuable model for the study of anthelmintic pharmacodynamics and drug-drug interactions: The case of ivermectin and eprinomectin. Suarez G et al. Front Pharmacol 2022. ONE

• Comparison of electrophysiological and motility assays to study anthelmintic effects in Caenorhabditis elegans. Hahnel SR et al. Int J Parasitol Drugs Drug Resist 2021. Ivermectin, moxidectin, milbemycin oxime, levamisole.  ONE

• Increased sensitivity of an infrared motility assay for nematicide discovery. Vairoletti F et al. Micropub biol 2021. Wact11. L1 stage. ONE

Natural compounds 

• Antibacterial, Antifungal, Antiviral, And Anthelmintic Activities Of Medicinal Plants Of Nepal Selected Based On Ethnobotanical Evidence. Joshi B et al. Evid Based Complement Alternat Med 2020. Plant extract screening, A. tomentosa, B. albiflora, K. pinnata, and D. integrifolia. ONE

• Active Principles Of Tetradenia Riparia. IV. Anthelmintic Activity Of 8(14),15-Sandaracopimaradiene-7α,18-Diol. Van Puyvelde L et al. J Ethnopharmacol 2018. bioassay-guided fractionation. ONE

• Bioassay-Guided Isolation of Anthelmintic Components from Semen pharbitidis, and the Mechanism of Action of Pharbitin. Liu M et al. Int J Mol Sci 2022. Bioassay-guided purification. ONE

NeuroDisease models

Caenorhabditis elegans is an attractive model organism in diverse fields of biology. One of the advantages of C. elegans is that it is feasible to generate “humanized” models of human diseases.Despite the lack of evolutionary complexity, there are a significant number of proteins that are evolutionary conserved between C. elegans and humans. It has been estimated that about 42% of the human disease genes have an orthologue in the genome of C. elegans including those genes associated with Alzheimer disease, Parkinson’s disease, muscular dystrophy, and many others disorders.

Neurodegenerative models usually involve the transgenic expression of human disease genes. In addition to being an excellent model to study diseases in the context of a whole organisms, C. elegans is compatible with high-throughput screenings for rapid and inexpensive drug discovery before boarding on expensive animal models.Methods that automate measure behavioral differences, as wMicrotracker ONE and ARENA systems, enables the study of human neurodegenerative disorders using ‘humanized worms’ and makes possible the screening of drugs.

alpha-Synuclein Toxicity

Accumulation of protein aggregates are a major hallmark of progressive neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. Transgenic Caenorhabditis elegans nematodes expressing the human synaptic protein α-synuclein in body wall muscle show inclusions of aggregated protein, which affects similar genetic pathways as in humans.

• Foldamers Reveal And Validate Novel Therapeutic Targets Associated With Toxic Α-Synuclein Self-Assembly. Ahmed J et al. Nature 2022. Parkinson, a-synuclein, NL5901, ARENA

• A 2D Fragment-Assisted Protein Mimetic Approach to Rescue α-Synuclein Aggregation Mediated Early and Post-Disease Parkinson’s Phenotypes. Stillman NH et al. bioRxiv 2022. Parkinson, a-synuclein, NL5901, UA196, ARENA

• Genetic Background Modifies Phenotypic And Transcriptional Responses In A C.Elegans Model Of Α-Synuclein Toxicity. Wang YA et al. BMC Genomics 2019. a-synuclein, ONE

Tau Aggregation

Tau is a neuron specific microtubule-associated protein that regulates microtubule stability, which is critical for axonal outgrowth and synaptic plasticity. In a pathological condition, tau dissociates from microtubules and forms insoluble aggregates called neurofibrillary tangles (NFTs).

• ARENA-Based Activity Profiling Of Tau And TDP-43 Transgenic C.Elegans. Currey HN et al. MicroPubl Biol 2020. ARENA

• A Novel Microtubule-Binding Drug Attenuates And Reverses Protein Aggregation In Animal Models Of Alzheimer’s Disease. Kakraba S et al. Front Mol Neurosci 2019. CL4176, ONE

MJD Disorder

Machado–Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an incurable disorder, widely regarded as the most common form of spinocerebellar ataxia in the world.

• Small Molecule Rescue of ATXN3 Toxicity in C. elegans via TFEB/HLH-30. Fardghassemi Y et al. Neurotherapeutics 2021. MAH240, ATXN3-CAG89 strain. Drug libraries: Sigma LOPAC library, MicroSource Discovery library, Biomol Natural Products library, Prestwick Chemical library. HTS. ONE

• Overexpression Of FKH-2/FOXG1 Is Neuroprotective In A C. Elegans Model Of Machado-Joseph Disease. Fardghassemi Y & Parker A. Exp Neurol 2021. ATXN3-CAG89 RNAi screening. ONE

ALS

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disorder in which the neuromuscular junction progressively degenerates, leading to movement difficulties, paralysis, and eventually death.

• The Novel Small Molecule TRVA242 Stabilizes Neuromuscular Junction Defects In Multiple Animal Models Of Amyotrophic Lateral Sclerosis. Bose P et al. Neurotherapeutics 2019. TDP-43. HTS. ONE
• Neurodegeneration in C. elegans models of ALS requires TIR-1/Sarm1 immune pathway activation in neurons. Julie Vérièpe et al. Nature communications 2015. TDP-43.  ONE

Toxicology

Animal behaviour depends upon integrated processes at the subcellular, cellular, and organismal level, and thus is susceptible of disruption by a broad spectrum of chemicals. Locomotor behaviour (movement) of the small free-living nematode C.elegans has proven to be useful in assessing toxicity. We can find literature about it on the field of Ecology, Pharmacology, Nanotechnology, Agrochemistry, drug development and many others.
Toxicity measures are easily implemented using our WMicrotracker system.

Developmental toxicology [wDAT method]

• C.elegans Development and Activity Test detects mammalian developmental neurotoxins. Hunt PR et al. Food Chem Toxicol 2018. HgOAc, wDAT: 12w continuous monitoring dev tox. ONE 
• Assessment of the effects of organic vs. inorganic arsenic and mercury in Caenorhabditis elegans. Camacho J. Curr Res Tox 2022. wDAT. ONE

• Contrasting dose response relationships of neuroactive antidepressants on the behavior of C. elegans. Van der Most MA. Ecotoxicol Environ Saf 2023. wDAT. ONE.

“ADMET like” using C. elegans

• Detoxification mechanisms of nickel sulfate in nematode Caenorhabditis elegans. Bowen T et al. Chemosphere 2020. NiSO4. ONE

• Reliable Screening of Dye Phototoxicity by Using a Caenorhabditis elegans Fast Bioassay. Bianchi JI et al. PLoS One 2015. Rose Bengal. ONE

Antioxidants

The nematode Caenorhabditis elegans has gained widespread recognition for its contribution to the study of various biological processes. Reactive oxygen species (ROS) play a complex role in this organism, including their involvement in signaling and the epigenetic regulation of gene expression. However, excessive levels of ROS can be harmful to cells and lead to oxidative stress, which is a major contributing factor in the development of numerous human diseases, such as diabetes, atherosclerosis, cancer, and aging. Consequently, the development of compounds that can reduce oxidative stress holds great potential for medical applications. The discovery of new antioxidants is of significant interest to both the pharmaceutical and food industries.

WMicrotracker is an automated measurement system specifically designed for studying stress responses. It enables researchers to conduct assays using various compounds, including hydrogen peroxide, paraquat, juglone, and sodium arsenite.

• Bioprospecting the Solar Panel Microbiome: High-Throughput Screening for Antioxidant Bacteria in a Caenorhabditis elegans Model. Kristie Tanner et al. Frontiers in Microbiology 2019. Hydrogen peroxide assay. ONE.
• Evaluation of WMircrotracker for assessing C.elegans stress responses. Master Thesis, University of Oslo 2016. Paraquat survival assay. ONE.

• Synthesis of 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones and their protective activity against oxidative stress. Monika Iškauskienė et al. Arch Pharm 2021. Juglone assay. ONE.

• End-of-life targeted degradation of DAF-2 insulin/IGF-1 receptor promotes longevity free from growth-related pathologies. Richard Venz et al. eLife 2021. Arsenite assay. ONE.

Lifespan and Healthspan

C. elegans offers several advantages for studying the biology of aging. The relatively short lifespan allows for genetic screenings, enabling the identification of underlying pathways associated with improvements in healthspan or lifespan. Using WMicrotracker ONE and ARENA, high-throughput measurements in liquid can be performed to assess the healthspan of worms. Additionally, SMART complements the results by allowing the performance of healthspan and lifespan assays on NGM

• Mitochondrial sulfide promotes life span and health span through distinct mechanisms in developing versus adult treated Caenorhabditis elegans. Vintila AR et al. Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2216141120. ONE
• A 2D Fragment-Assisted Protein Mimetic Approach to Rescue αSynuclein Aggregation Mediated Early and Post-Disease
  Parkinson’s Phenotypes. Stillman NH et al. bioRxiv 2022.07.11.499659. [Fig4-5] ARENA
• Muscle-Specific Lipid Hydrolysis Prolongs Lifespan Through Global Lipidomic Remodeling. Schmeisser S et al. Cell Rep. 2019 Dec 24;29(13):4540-4552.e8. ONE
• Regulation Of Lifespan By Neural Excitation And REST. Zullo JM et al. Nature. 2019 Oct;574(7778):359-364. ONE
• FET Proteins Regulate Lifespan And Neuronal Integrity. Therrien M et al. Scientific Reports volume 6, Article number: 25159 (2016). ONE
• Lifespan assay using SMART has not been published yet, but we have sold more than 30 units last year and expect publications soon.You will find internal example here.

Technology use comparison: