Many heard
about Caenorhabditis elegans (C. elegans)
when they survived even as space shuttle Columbia was ripped apart in its
final flight in 2003. But the legacy of this tiny nematode dates back to early
1960s.
Approximately 25,000 peer reviewed
publications have used C. elegans as an
experimental model organism. More than a thousand research papers have already
been published in 2015 with work revolving around C. elegans. It was the first
multi cellular organism to have its entire genome
sequenced and the only organism to have its neural connectome fully
mapped. Between 2002 and 2008, three of the Nobel Prize winning discoveries
were on C. elegans. Two encyclopedias
on this organism have been published in 1988
and 1997
with numerous reprints which still serve as invaluable resources for
researchers worldwide. Moreover, an online review portal, WormBook consolidates all the works done on
C. elegans. There is even an
extensive repository of the genomic, transcriptomic and proteomic data of C. elegans, WormBase, accessible globally to
scientific curators. This is updated fortnightly, more frequently than any
other molecular biology database in the world. Thousands of scientists and
hundreds of millions of dollars are involved in C. elegans work around the globe. National Institutes of Health has
a dedicated initiative
for C. elegans research. For a 1mm
non-parasitic nematode feeding on bacteria in rotten organic matter, it is an
insignificant organism in nature. But why does the scientific community of life
sciences and chemistry work so profoundly on it?
It was in 1963 that Sydney
Brenner first proposed C. elegans as the model organism for
his studies on the molecular and developmental biology of neural systems. The
choice was very crucial. Brenner chose C.
elegans for many reasons. He was immensely attracted by the very fact that
thousands of this soil-dwelling nematode could be easily grown in a bed of E.
coli in a petri dish within the laboratory unlike mouse, rats or higher animals.
Moreover, being a hermaphrodite, these organisms self-fertilized and inbred
300-350 offspring per reproductive cycle of just three days. The added advantage
came with the knowledge that, they could even be cross-bred with male worms for
genetic hybrids. Only plant geneticists enjoyed the convenience of crossing and
selfing till then. The total number of cells in the body of this worm is always
fixed at 959 in an adult hermaphrodite and 1031 in the adult male. Of these 302
cells are consistently neurons. They form a primitive nervous system with a
‘brain’ of circumpharyngeal nerve ring. This can be easily traced with the
contrast optics of serial section electron microscopy. The organism is thus
equidistant from complexity and simplicity. The transparency of body gives the
unique opportunity to track cellular differentiation and developmental
processes even in the intact organism under a simple microscope. Anatomic
simplicity, short life span of less than three weeks, fully sequenced 20,470
distinct genes with 50% homology to human genome and long term storage
feasibility and easy transportability; C. elegans is one of the best model
systems in experimental cellular biology.
Sydney Brenner, H Robert Horvitz and
John E Sulston received the Nobel Prize in Physiology or Medicine in 2002 for their
work in “genetic regulation of organ development and programmed cell death”.
They found out that 131 cells present during the early embryonic stages of the
worm were absent in the adult and traced these cell lineages throughout the
life span of the worm to postulate their theories on the programmed cell death
or apoptosis. Starting from the discovery of nuc-1 by Sulston and ced-3 and ced-4 by
Horvitz, this paved way to the identification of many pro and anti apoptotic
genes. Later, asymmetric cell division and the fate of each cell during
embryogenesis was extensively
mapped using C. elegans. DNA
recombinations as well as DNA repair mechanisms have been described using the
same model organism. Andrew Fire and Craig C Mello worked extensively on
genetic interference by hybridization of exogenous double stranded RNA with
endogenous mRNA transcripts (RNA
interference; RNAi) in C. elegans
which earned them the Nobel Prize in Physiology or Medicine in 2006. In fact, C.elegans is one of the first multi
cellular transgenic animals created in laboratory settings. Peculiar gut
granules of C. elegans emit fluorescence
and even cause a fluorescence burst at the time of death of the worm. Martin
Chalfie was awarded the Nobel Prize in Chemistry in 2008 for his
work on green fluorescent proteins as a marker of gene expression. He did
much of his work using C. elegans.
From nucleotide base pairing in DNA to genetic basis of muscle atrophy in zero
gravity space, C. elegans is helping researchers worldwide to understand
the intricacies of molecular biology and genetics.
Interestingly, WormBase has declared prize
worth $5000 to anyone who comes up with a better model organism than C. elegans!
