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Nematode Worms (Caenorhabditis Elegans): Difference between revisions
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In 1963, [[Sydney Brenner]] proposed research into ''C. elegans,'' primarily in the area of neuronal development. In 1974, he began research into the [[molecular biology|molecular]] and [[developmental biology]] of ''C. elegans'', which has since been extensively used as a [[model organism]].{{pmid|4366476}} It was the first [[multicellular organism]] to have its [[whole genome sequencing|whole genome sequenced]], and in 2019 it was the first organism to have its [[connectome]] (neuronal "wiring diagram") completed.{{pmid|22462104}}{{pmid|23801597}}<ref>{{cite magazine |last=Jabr |first=Ferris | name-list-style = vanc |date=2012-10-02 |title=The Connectome Debate: Is Mapping the Mind of a Worm Worth It? |url=https://www.scientificamerican.com/article/c-elegans-connectome/ |magazine=Scientific American |access-date=2014-01-18}}</ref> | In 1963, [[Sydney Brenner]] proposed research into ''C. elegans,'' primarily in the area of neuronal development. In 1974, he began research into the [[molecular biology|molecular]] and [[developmental biology]] of ''C. elegans'', which has since been extensively used as a [[model organism]].{{pmid|4366476}} It was the first [[multicellular organism]] to have its [[whole genome sequencing|whole genome sequenced]], and in 2019 it was the first organism to have its [[connectome]] (neuronal "wiring diagram") completed.{{pmid|22462104}}{{pmid|23801597}}<ref>{{cite magazine |last=Jabr |first=Ferris | name-list-style = vanc |date=2012-10-02 |title=The Connectome Debate: Is Mapping the Mind of a Worm Worth It? |url=https://www.scientificamerican.com/article/c-elegans-connectome/ |magazine=Scientific American |access-date=2014-01-18}}</ref> | ||
== Use as a Model Organism == | |||
In 1963, Sydney Brenner proposed using ''C. elegans'' as a [[Model Organisms|model organism]] for the investigation primarily of neural development in animals. It is one of the simplest organisms with a nervous system. The neurons do not fire action potentials, and do not express any voltage-gated sodium channels.{{pmid|11084387}} In the hermaphrodite, this system comprises 302 neurons{{pmid|17572666}} the pattern of which has been comprehensively mapped,{{pmid|31270481}} in what is known as a connectome,<ref name="Brouillette">{{cite journal |last1=Brouillette |first1=Monique |title=Mapping the brain to understand the mind |journal=Knowable Magazine {{!}} Annual Reviews |date=21 April 2022 |doi=10.1146/knowable-042122-1|doi-access=free |url=https://knowablemagazine.org/article/mind/2022/mapping-brain-understand-mind |language=en}}</ref> and shown to be a small-world network.{{pmid|9623998}} | |||
Research has explored the neural and molecular mechanisms that control several behaviors of ''C. elegans'', including chemotaxis, thermotaxis, mechanotransduction, learning, memory, and mating behaviour.{{pmid|16139205}} In 2019 the connectome of the male was published using a technique distinct from that used for the hermaphrodite. The same paper used the new technique to redo the hermaphrodite connectome, finding 1,500 new synapses.{{pmid|31270481}} | |||
It has been used as a model organism to study molecular mechanisms in metabolic diseases.{{pmid|29990370}} Brenner also chose it as it is easy to grow in bulk populations, and convenient for genetic analysis.<ref>{{cite web |last=Avery |first=L |title=Sydney Brenner |url=http://elegans.swmed.edu/Sydney.html |publisher=[[Southwestern Medical Center]] |url-status=dead |archive-url=https://web.archive.org/web/20110815143145/http://elegans.swmed.edu/Sydney.html |archive-date=August 15, 2011 }} [http://elegans.som.vcu.edu/Sydney.html Alt. URL] {{Webarchive|url=https://web.archive.org/web/20131208060434/http://elegans.som.vcu.edu/Sydney.html |date=2013-12-08 }}</ref> It is a multicellular eukaryotic organism, yet simple enough to be studied in great detail. The transparency of ''C. elegans'' facilitates the study of cellular differentiation and other developmental processes in the intact organism. The spicules in the male clearly distinguish males from females. Strains are cheap to breed and can be frozen. When subsequently thawed, they remain viable, allowing long-term storage.<ref name="ReferenceB" /> Maintenance is easy when compared to other multicellular model organisms. A few hundred nematodes can be kept on a single agar plate and suitable growth medium. Brenner described the use of a mutant of ''E. coli'' – OP50. OP50 is a uracil-requiring organism and its deficiency in the plate prevents the overgrowth of bacteria which would obscure the worms.{{pmid|4366476}} The use of OP50 does not demand any major laboratory safety measures, since it is non-pathogenic and easily grown in Luria-Bertani (LB) media overnight.<ref>{{Cite web|url=http://www.wormbook.org/chapters/www_behavior/behavior.html#sec1|title=Behavior|website=www.wormbook.org|access-date=2018-09-26}}</ref> | |||
===Ageing=== | |||
''C. elegans'' has been a model organism for research into ageing; for example, the inhibition of an insulin-like growth factor signaling pathway has been shown to increase adult lifespan threefold;{{pmid|11021802}}{{pmid|25517099}} while glucose feeding promotes oxidative stress and reduce adult lifespan by a half.<ref name="ReferenceC" /> Similarly, induced degradation of an insulin/IGF-1 receptor late in life extended life expectancy of worms dramatically.{{pmid|34505574}} Long-lived mutants of ''C. elegans'' were demonstrated to be resistant to oxidative stress and UV light.{{pmid|18203746}} These long-lived mutants had a higher DNA repair capability than wild-type ''C. elegans''.<ref name="Hyun2008" /> Knockdown of the nucleotide excision repair gene Xpa-1 increased sensitivity to UV and reduced the life span of the long-lived mutants. These findings indicate that DNA repair capability underlies longevity. | |||
The capacity to repair DNA damage by the process of nucleotide excision repair declines with age.{{pmid|17472752}} | |||
''C. elegans'' exposed to 5mM lithium chloride (LiCl) showed lengthened life spans.{{pmid|17959600}} When exposed to 10μM LiCl, reduced mortality was observed, but not with 1μM.{{pmid|21301855}} | |||
''C. elegans'' has been instrumental in the identification of the functions of genes implicated in Alzheimer's disease, such as presenilin.{{pmid|20012092}} Moreover, extensive research on ''C. elegans'' has identified RNA-binding proteins as essential factors during germline and early embryonic development.{{pmid|21402787}} | |||
Telomeres, the length of which have been shown to correlate with increased lifespan and delayed onset of [[Senecent Cells|senescence]] in a multitude of organisms, from ''C. elegans''<ref>{{Cite journal|last1=Coutts|first1=Fiona|last2=Palmos|first2=Alish B.|last3=Duarte|first3=Rodrigo R. R.|last4=de Jong|first4=Simone|last5=Lewis|first5=Cathryn M.|last6=Dima|first6=Danai|last7=Powell|first7=Timothy R.|date=March 2019|title=The polygenic nature of telomere length and the anti-ageing properties of lithium|journal=Neuropsychopharmacology|volume=44|issue=4|pages=757–765|doi=10.1038/s41386-018-0289-0|issn=1740-634X|pmc=6372618|pmid=30559463}}</ref><ref>{{Cite journal|last1=Raices|first1=Marcela|last2=Maruyama|first2=Hugo|last3=Dillin|first3=Andrew|last4=Karlseder|first4=Jan|date=September 2005|title=Uncoupling of longevity and telomere length in C. elegans|journal=PLOS Genetics|volume=1|issue=3|pages=e30|doi=10.1371/journal.pgen.0010030|issn=1553-7404|pmc=1200426|pmid=16151516 |doi-access=free }}</ref> to humans,<ref>{{Cite journal|last1=Lulkiewicz|first1=M.|last2=Bajsert|first2=J.|last3=Kopczynski|first3=P.|last4=Barczak|first4=W.|last5=Rubis|first5=B.|date=September 2020|title=Telomere length: how the length makes a difference|journal=Molecular Biology Reports|volume=47|issue=9|pages=7181–7188|doi=10.1007/s11033-020-05551-y|issn=1573-4978|pmc=7561533|pmid=32876842}}</ref> show an interesting behaviour in ''C. elegans.'' While ''C. elegans'' maintains its telomeres in a canonical way similar to other eukaryotes, in contrast ''[[Dros'' | |||
[[Telomere]]s, the length of which have been shown to correlate with increased lifespan and delayed onset of [[senescence]] in a multitude of organisms, from ''C. elegans''{{pmid|30559463}}{{pmid|16151516}} to humans,{{pmid|32876842}} show an interesting behaviour in ''C. elegans.'' While ''C. elegans'' maintains its telomeres in a canonical way similar to other eukaryotes, in contrast ''[[Drosophila melanogaster]]'' is noteworthy in its use of [[retrotransposon]]s to maintain its telomeres,{{pmid|21821789}} during [[Gene knockout|knock-out]] of the [[Telomerase reverse transcriptase|catalytic subunit of the telomerase (''trt-1'')]] ''C. elegans'' can gain the ability of alternative telomere lengthening (ALT). ''C. elegans'' was the first eukaryote to gain ALT functionality after knock-out of the canonical [[telomerase]] pathway.{{pmid|16477310}} ALT is also observed in about 10-15% of all clinical cancers.{{pmid|20351727}} Thus ''C. elegans'' is a prime candidate for ALT research.{{pmid|27593554}}{{pmid|23390606}}{{pmid|27761361}} Bayat et al. showed the paradoxical shortening of telomeres during ''[[Telomerase reverse transcriptase|trt-1]]'' [[over-expression]] which lead to near [[Sterility (physiology)|sterility]] while the worms even exhibited a slight increase in lifespan, despite shortened telomeres.{{pmid|31954861}} | |||
==See Also== | ==See Also== | ||