scholarly journals Model super-organisms: Can the biochemical genetics of E. coli help us understand aging?

2015 ◽  
Vol 37 (4) ◽  
pp. 12-15
Author(s):  
David Weinkove
Keyword(s):  
Biosynthetic Pathway ◽  
Model Organism ◽  
Toxin Production ◽  
Enzyme Function ◽  
Nutrient Media ◽  
E Coli ◽  
C Elegans ◽  
Biochemical Pathways ◽  
Nematode Worm ◽  
Worm Caenorhabditis Elegans

Escherichia coli is a powerful model organism to help us understand biochemical pathways and enzyme function. In E. coli, biosynthetic pathway mutants are conditionally viable depending on the composition of the nutrient media. Genetic analysis allows enzyme function to be linked to gene sequences. E. coli is used in the lab as a food source for the nematode worm Caenorhabditis elegans, a model organism for the understanding of basic animal biology. Recent work has shown that specific biosynthetic pathways in E. coli can influence C. elegans aging. Careful experimentation is needed to determine whether E. coli biochemistry influences aging by altering C. elegans nutrition or through changes to bacterial functions, such as toxin production. Understanding these interactions in the C. elegans–E. coli model “super-organism” will inform studies of how bacteria of the human microbiota interact with the host.

Intestinal Ca2+ wave dynamics in freely moving C. elegans coordinate execution of a rhythmic motor program

2008 ◽  
Vol 294 (1) ◽  
pp. C333-C344 ◽  
Author(s):  
K. Nehrke ◽  
Jerod Denton ◽  
William Mowrey
Keyword(s):  
Model Organism ◽  
Motor Program ◽  
Wave Dynamics ◽  
C Elegans ◽  
Plasmic Reticulum ◽  
Rhythmic Behavior ◽  
Freely Behaving ◽  
Trisphosphate Receptor ◽  
Nematode Worm ◽  
Worm Caenorhabditis Elegans

Defecation in the nematode worm Caenorhabditis elegans is a highly rhythmic behavior that is regulated by a Ca2+ wave generated in the 20 epithelial cells of the intestine, in part through activation of the inositol 1,4,5-trisphosphate receptor. Execution of the defecation motor program (DMP) can be modified by external cues such as nutrient availability or mechanical stimulation. To address the likelihood that environmental regulation of the DMP requires integrating distinct cellular and organismal processes, we have developed a method for studying coordinate Ca2+ oscillations and defecation behavior in intact, freely behaving animals. We tested this technique by examining how mutations in genes known to alter Ca2+ handling [including egl-8/phospholipase C (PLC)-β, kqt-3/KCNQ1, sca-1/sarco(endo)plasmic reticulum Ca2+ ATPase, and unc-43/Ca2+-CaMKII] contribute to shaping the Ca2+ wave and asked how Ca2+ wave dynamics in the mutant backgrounds altered execution of the DMP. Notably, we find that Ca2+ waves in the absence of PLCβ initiate ectopically, often traveling in reverse, and fail to trigger a complete DMP. These results suggest that the normal supremacy of the posterior intestinal cells is not obligatory for Ca2+ wave occurrence but instead helps to coordinate the DMP. Furthermore, we present evidence suggesting that an underlying pacemaker appears to oscillate at a faster frequency than the defecation cycle and that arrhythmia may result from uncoupling the pacemaker from the DMP rather than from disrupting the pacemaker itself. We also show that chronic elevations in Ca2+ have limited influence on the defecation period but instead alter the interval between successive steps of the DMP. Finally, our results demonstrate that it is possible to assess Ca2+ dynamics and muscular contractions in a completely unrestrained model organism.

scholarly journals From pathogen to commensal to probiotic: modification of Microbacterium nematophilum-C. elegans interaction during chronic infection by the absence of host insulin signalling

2020 ◽  
Author(s):  
Maria Gravato-Nobre ◽  
Jonathan Hodgkin ◽  
Petros Ligoxygakis
Keyword(s):  
Chronic Infection ◽  
Insulin Signalling ◽  
Avirulent Strain ◽  
Opportunistic Pathogens ◽  
E Coli ◽  
C Elegans ◽  
Intestinal Infections ◽  
Age Dependent ◽  
Immune Defences ◽  
Nematode Worm

ABSTRACTThe nematode worm Caenorhabditis elegans depends on microbes in decaying vegetation as its food source. To survive in an environment rich in opportunistic pathogens, C. elegans has evolved an epithelial defence system where surface-exposed tissues such as epidermis, pharynx, intestine, vulva and hindgut have the capacity of eliciting appropriate immune defences to acute gut infection. However, it is unclear how the worm responds to chronic intestinal infections. To this end, we have surveyed C. elegans mutants that are involved in inflammation, immunity and longevity to find their phenotypes during chronic infection. Worms that grew in a monoculture of the natural pathogen Microbacterium nematophilum (CBX102 strain) had a reduced lifespan and health span. This was independent of intestinal colonisation as both CBX102 and the derived avirulent strain UV336 were early persistent colonisers. In contrast, long-lived daf-2 mutants were resistant to chronic infection, showing reduced colonisation and a higher age-dependent vigour. In fact, UV336 acted as a probiotic in daf-2, showing a lifespan extension beyond OP50, the E. coli strain used for laboratory C. elegans culture. Longevity and vigour of daf-2 mutants growing on CBX102 was dependent on the FOXO orthologue DAF-16. Since the DAF-2/DAF-16 axis is present in most metazoans this suggests an evolutionary conserved host mechanism to modify a pathogen to a commensal.

scholarly journals Folic acid preventsC. elegansfolate deficiency indirectly via bacterial uptake of a breakdown product: a route that can also increase bacterial toxicity and ageing

2017 ◽  
Author(s):  
Claire Maynard ◽  
Ian Cummins ◽  
Jacalyn Green ◽  
David Weinkove
Keyword(s):  
Folic Acid ◽  
Folate Deficiency ◽  
Breakdown Product ◽  
E Coli ◽  
C Elegans ◽  
Bacterial Uptake ◽  
Major Route ◽  
Bacterial Toxicity ◽  
Health Complications ◽  
Nematode Worm

AbstractSupplementation with the synthetic oxidised folate, folic acid is used to prevent neural tube defects and other symptoms of folate deficiency. However, several unanswered questions remain over folic acid efficacy, safety and interactions with gut microbes. Prevention of a development defect caused by folate deficiency in the nematode wormCaenorhabditis elegansrequires > 10 fold higher concentrations of folic acid compared to folinic acid, a reduced folate. Here we show that the major route for folic acid to restore normal development is indirect via theEscherichia coliused to feedC. elegans.This route occurs mainly via theE. colitransporter AbgT, which takes up the folic acid breakdown product para-aminobenzoate-glutamate (PABA-glu). We found that folic acid preparations, including a commercial supplement, contain 0.3- 4.0 % of this breakdown product. Previously, we have shown that inhibiting bacterial folate synthesis increasesC. eleganslifespan by removing a life-shortening bacterial activity. Here, we show that folic acid restores bacterial folate synthesis and reverses this lifespan increase. It is still to be determined whether this bacterial route increases host folate levels in humans and if there are situations where increased bacterial folate synthesis has negative health complications.

5. Uncontrolled Cell Division and Migration of Q neuroblasts in mutant strains of C. elegans

2018 ◽  
Author(s):  
Brandon Lam
Keyword(s):  
Cell Division ◽  
Cell Metabolism ◽  
Model Organism ◽  
C Elegans ◽  
Mutant Strains ◽  
Increase Risk ◽  
And Migration ◽  
Nematode Worm

Cancer is one of the most prevalent and deadly diseases in today's society, affecting millions of people around the globe. Uncontrolled cell division and migration which are two of the six major hallmarks of cancer have been studied extensively in vitro, however in vivo these hallmarks are not well understood. We used the Caenorhabditis elegans nematode worm as our model organism in order to study these two hallmarks. In unfavorable environmental conditions such as starvation, C. elegans can enter a developmental arrest in where certain cell metabolism ceases to continue, this stage is known as L1 arrest. Normally in L1 arrested worms, there are 2 distinct Q neuroblast cells which are precursors of sensory and interneurons that do not divide and migrate. However, when we mutate certain genes, we noticed that the two Q neuroblasts inappropriately divided and migrated, this suggests that we have identified a good model to study uncontrolled cell division and migration. We have already found one gene that when mutated, results in the Q neuroblasts inappropriately dividing and migrating at L1 arrest, now we are looking for other mutated genes that can cause this phenotype, this ultimately allows us to identify new mechanisms that cause an increase risk in cancer.​

The glycomes of Caenorhabditis elegans and other model organisms

2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell
Keyword(s):  
Caenorhabditis Elegans ◽  
Current Knowledge ◽  
Structural Data ◽  
Model Organisms ◽  
Entire Genome ◽  
C Elegans ◽  
The Face ◽  
Area Of Concern ◽  
Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

scholarly journals Health and longevity studies in C. elegans: the “healthy worm database” reveals strengths, weaknesses and gaps of test compound-based studies

2021 ◽  
Vol 22 (2) ◽  
pp. 215-236
Author(s):  
Nadine Saul ◽  
Steffen Möller ◽  
Francesca Cirulli ◽  
Alessandra Berry ◽  
Walter Luyten ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Model Organism ◽  
Research Field ◽  
Aging Research ◽  
Genetic Manipulations ◽  
C Elegans ◽  
Starting Point ◽  
Health Related ◽  
Phenotype Measurement ◽  
Or Gene

AbstractSeveral biogerontology databases exist that focus on genetic or gene expression data linked to health as well as survival, subsequent to compound treatments or genetic manipulations in animal models. However, none of these has yet collected experimental results of compound-related health changes. Since quality of life is often regarded as more valuable than length of life, we aim to fill this gap with the “Healthy Worm Database” (http://healthy-worm-database.eu). Literature describing health-related compound studies in the aging model Caenorhabditis elegans was screened, and data for 440 compounds collected. The database considers 189 publications describing 89 different phenotypes measured in 2995 different conditions. Besides enabling a targeted search for promising compounds for further investigations, this database also offers insights into the research field of studies on healthy aging based on a frequently used model organism. Some weaknesses of C. elegans-based aging studies, like underrepresented phenotypes, especially concerning cognitive functions, as well as the convenience-based use of young worms as the starting point for compound treatment or phenotype measurement are discussed. In conclusion, the database provides an anchor for the search for compounds affecting health, with a link to public databases, and it further highlights some potential shortcomings in current aging research.

scholarly journals Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the Mouse

2021 ◽  
Vol 22 (3) ◽  
pp. 1015
Author(s):  
Vu Thu Thuy Nguyen ◽  
Jason Sallbach ◽  
Malena dos Santos Guilherme ◽  
Kristina Endres
Keyword(s):  
Calcium Influx ◽  
Ex Vivo ◽  
Model Organism ◽  
Nmda Receptor Antagonist ◽  
Acetylcholine Esterase ◽  
Enteric Neurons ◽  
Acetylcholine Esterase Inhibitors ◽  
E Coli ◽  
Esterase Inhibitors ◽  
Intestinal Functions

Four drugs are currently approved for the treatment of Alzheimer’s disease (AD) by the FDA. Three of these drugs—donepezil, rivastigmine, and galantamine—belong to the class of acetylcholine esterase inhibitors. Memantine, a NMDA receptor antagonist, represents the fourth and a combination of donepezil and memantine the fifth treatment option. Recently, the gut and its habitants, its microbiome, came into focus of AD research and added another important factor to therapeutic considerations. While the first data provide evidence that AD patients might carry an altered microbiome, the influence of administered drugs on gut properties and commensals have been largely ignored so far. However, the occurrence of digestive side effects with these drugs and the knowledge that cholinergic transmission is crucial for several gut functions enforces the question if, and how, this medication influences the gastrointestinal system and its microbial stocking. Here, we investigated aspects such as microbial viability, colonic propulsion, and properties of enteric neurons, affected by assumed intestinal concentration of the four drugs using the mouse as a model organism. All ex vivo administered drugs revealed no direct effect on fecal bacteria viability and only a high dosage of memantine resulted in reduced biofilm formation of E. coli. Memantine was additionally the only compound that elevated calcium influx in enteric neurons, while all acetylcholine esterase inhibitors significantly reduced esterase activity in colonic tissue specimen and prolonged propulsion time. Both, acetylcholine esterase inhibitors and memantine, had no effect on general viability and neurite outgrowth of enteric neurons. In sum, our findings indicate that all AD symptomatic drugs have the potential to affect distinct intestinal functions and with this—directly or indirectly—microbial commensals.

Benefits of Using the Invertebrate Model Organism C. Elegans in an Inquiry-Based Laboratory Activity

2021 ◽  
pp. 009862832110296
Author(s):  
Angy J. Kallarackal
Keyword(s):  
American Psychological Association ◽  
Model Organism ◽  
Learning Goals ◽  
Research Skills ◽  
Final Exam ◽  
Laboratory Activity ◽  
Writing Ability ◽  
C Elegans ◽  
Invertebrate Model ◽  
Laboratory Experiences

Background: The goals of laboratory experiences include developing knowledge base, research skills, and scientific communication abilities. Objective: The aim was to assess an inquiry-based laboratory activity using the model organism Caenorhabditis elegans in relation to learning goals. Method: Students in a Biopsychology laboratory course worked in groups to test the effect of various drugs (e.g., nicotine, ethanol, fluoxetine, and melatonin) on C. elegans behavior. The activity included literature review, experimental design, and a final lab report. A cumulative final exam included a synaptic communication question related to the content of the activity. Results: Students showed better retention of laboratory-related content compared to other topics from the course, as demonstrated through performance on the final exam and were able to replicate previous research demonstrating effects of drug on locomotion. However, students did not improve writing ability compared to performance on a previous American Psychological Association style lab report. Conclusion: This study demonstrates that using a student-designed, multi-week laboratory assignment in an undergraduate Biopsychology course supports the growth of psychology knowledge and the development of research skills. Teaching Implications: Instructors should consider using the described laboratory activity for biopsychology or behavioral neuroscience classes or consider similarly designed laboratory formats for other courses in Psychology.

Sign in / Sign up

Export Citation Format

Share Document