The Nematode Caenorhabditis Elegans |
Posted: February 9, 2023 |
The nematode Caenorhabditis elegans is one of the most studied organisms in the world, and it has become an important tool to solve a wide range of biological problems. Its cellular physiology and genetic tools have allowed scientists to explore the development of cells, organs, and tissues in the body of this tiny animal. Despite its small size, it contains a complex nervous system that can be used to study many aspects of behavior in a simple animal. For example, it is able to learn and remember complex tasks and has been shown to have long-term memory and choice selection behaviors. Nematodes are also ideal models for studying stress resistance and aging because their lifespans can be prolonged by manipulation of various pathways and proteins that affect oxidative stress and DNA repair. For instance, reducing oxidative stress by feeding on glucose prolongs worms' life span, and knocking down an insulin/IGF-1 signaling pathway in the late stages of a worm's life extends lifespan dramatically (Stiernagle 2006). C. elegans can mount defensive responses to pathogen infection through evolutionarily conserved cellular signaling pathways that activate immune effectors such as lectins, lysozymes, lipases, and antimicrobial peptides, which protect against invading microbes. This defense mechanism is mediated by the intestinal and epidermal epithelial cells that are in direct contact with different microbes. The worm's basic anatomy is based on an unsegmented, vermiform, and bilaterally symmetrical form with four main epidermal cords and a fluid-filled pseudocoelom. It lacks a heart, lungs, and kidney and is primarily an ovo-vegative hermaphrodite. Its spermatheca is an amoeboid and lacks flagella and acrosomes. It is highly amenable to genetic manipulation, and the worm's transparency allows researchers to easily study colonization of putative commensal bacteria that may play a role in host health and longevity, such as Comamonas and Bacillus subtilis (Clark and Hodgkin, 2014). The nematode is also sensitive to antibiotic treatment, allowing the Shapira laboratory to identify gut microbes that protect against P. aeruginosa infection, slowing colonization and killing of the worm (Montalvo-Katz et al., 2013). These worms are also good model systems for studying disease and drug responses, because they share a high number of genes and signaling pathways with humans. For instance, it has been shown that mitochondrial dysfunction in C. elegans is associated with diseases such as maple syrup urine disease and Leigh syndrome, a condition in which the body lacks ATP production because of an impaired oxidative phosphorylation process. Proteins that regulate gene expression and metabolites involved in energy production are also well understood in this model system. For example, it is known that the protein synthesis-dependent transcription factor (TF) RtcB has multiple functions. For example, it can activate and repress gene expression by binding to complementary DNA sequences and by interacting with other TFs that have similar or opposite regulatory functions. Similarly, it is known that the TFs APOL and TAPO repress and activate gene expression by binding to complementary DNA sequences. For example, APOL binds to DNA sequences that code for amino acids and TAPO binds to similar sequences that encode proteins that play a role in oxidative stress and lipid metabolism. These interactions may explain the ability of these TFs to act redundantly, repressing or activating each other's functions in a coordinated way.
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