Size doesn’t matter. Certainly not in terms of tiny worms securing the eye of biologists. One such biologist, Morris F. Maduro on the University of California, Riverside, has simply been awarded a grant of practically $1.3 million from the National Science Foundation, or NSF, to review a worm (or nematode) a few millimeter in size.
The analysis venture will deal with the intestine of Pristionchus pacificus. Like most nematodes, P. pacificus develops rapidly, its progress from embryo to grownup taking simply 4 days. It is a whole animal, with a nervous system, pores and skin, gut, and muscle tissues. Nematodes of the genus Pristionchus are a distant relative of the well-studied species Caenorhabditis elegans, utilized by biologists as a mannequin organism to review animal growth and conduct.
Funded for 4 years, the analysis venture will deal with adjustments within the gene community that specify the early intestinal precursor cells in nematodes like P. pacificus. Gene networks describe how genes flip one another on and off. Precursor cells are stem cells that may differentiate — or specialize — into just one cell sort.
“During embryonic development, gene networks cause cells to develop along pathways of differentiation, resulting in cells becoming specialized in their function,” mentioned Maduro, a professor of molecular, cell and systems biology who has studied nematodes for greater than twenty years. “Changes in such networks occur over evolutionary time and in human disease. For more than 25 years, gut specification was studied in only a single species, C. elegans, and its close relatives. The NSF grant will allow us to extend our work into the genus Pristionchus.”
P. pacificus is normally present in affiliation with a species of scarab beetle, whereas C. elegans is free-living and normally discovered on rotting fruit. P. pacificus has some diversifications, resembling a mouth with just a little tooth for consuming the corpses of lifeless beetles. As a consequence, P. pacificus can attack different nematodes and is extra predatory than C. elegans. C. elegans tends to eat largely micro organism and fungi.
“Pristionchus embryos look a like those of C. elegans,” Maduro mentioned. “But even when the phenotype, the outward form of the animal, doesn’t change, the genes behind the scenes can still change. This phenomenon is called developmental system drift, paralleling the term genetic drift. Entire sets of genes can change while their overall function does not. In other words, the endpoint, whether it’s C. elegans or P. pacificus or another nematode species, still looks like a nematode. This means Pristionchus makes its gut in a different way than C. elegans. This idea that genes change when the phenotype looks the same among species is probably quite widespread.”
Eric S. Haag, a professor of biology on the University of Maryland who won’t be taking part within the analysis venture, mentioned he’s excited to study extra about Maduro’s work.
“Biologists have long sought to understand how new features of animal bodies get encoded by new genomic instructions. But we now know that even the genes that construct ancient traits still undergo evolutionary changes,” Haag mentioned. “Dr. Maduro’s work uses a very manipulable type of nematode to explore this paradoxical fact. Within a group of worms with very similar digestive systems, some species have re-invented the genetic circuits that control their development. It’s so surprising, and I can’t wait to learn about what they find.”
Maduro defined that gene community adjustments can happen resulting from mutations or an infection and might result in illnesses resembling most cancers.
“Nematodes are a powerful model system for us to study how gene networks can change, because we can get answers inexpensively and on a short time scale,” he mentioned. “By comparing Pristionchus and C. elegans, we hope to learn fundamental principles about how gene networks can become more complex.”
The venture will use a mixture of bioinformatic and genetics strategies to grasp how the easy embryonic gene community in an ancestral Pristionchus species underwent enlargement over evolutionary time to kind a extra advanced community.
“Two technologies have allowed researchers to address the explosion of this and other evolutionary questions we see today,” Maduro mentioned. “They are (a) rapid genome sequencing at low cost and (b) the ability to use CRISPR to knock out genes in the genome at low cost and high efficiency.”
Maduro added that nematode species may be present in almost each ecological area of interest on Earth.
“There are maybe a million different species,” he mentioned. “We can only study a small number of them. Pristionchus garnered scientific interest only about 25 years ago and research took off in earnest in the past decade when CRISPR became available to simplify gene editing. P. pacificus has three genes that specify the gut, but other related species have fewer genes. We have an opportunity to study the stepwise evolution of how this network got bigger and more complicated.”
Preliminary work in Maduro’s lab recognized two of those three expanded genes in Pristionchus. When the gene pair was deleted, the intestine disappeared in about half of the worms.
“We now need to delete that third gene to make sure we know that’s the only other gene that leads to gut specification,” Maduro mentioned. “This grant will help us do that.”
The venture will present educating and coaching alternatives for graduate and undergraduate college students, together with by means of a freshman laboratory course in nematode genetics, bioinformatics, microscopy, and molecular biology. Four undergraduate college students will obtain summer time help for annually of the grant to work on initiatives associated to Pristionchus. The grant will help as much as two graduate college students. Maduro will probably be assisted within the analysis by his spouse, Gina Broitman-Maduro, an affiliate specialist in his lab. The begin date of the grant is January 15, 2024.
Header picture exhibits Morris Maduro (standing) and Gina Broitman-Maduro. (UCR/Stan Lim)
