Molting
Molting involves the replacement of an animal’s exoskeleton to allow further growth and is an essential developmental process in Ecdysozoans, such as arthropods and nematodes. The study of molting provides a window into the developmental program of core cellular processes, such as oscillatory gene expression, coordinated intracellular trafficking, steroid hormone signaling, developmental timing, and apical extracellular matrix (aECM) remodeling. Nematode cuticles are a collagen-based aECM similar to mammalian ECMs; thus, understanding aECM dynamics during molting can inform mammalian dermal physiology, wound healing, and tumor invasion through the ECM.
Projects in the lab focus on how key developmental regulators such as NHR-23 and LIN-42 oscillate during each larval stage and how they control downstream target genes to coordinate molting and stage-specific developmental events. Another project focuses on how NHR-23-regulated proteases and protease inhibitors are coordinated to remodel the aECM during each larval stage. We are also exploring whether a ligand regulates molting. Our data and those of others suggest that NHR-23 likely sits as the top of a hierarchy of transcriptional regulation for molting. Moreover, its insect ortholog is involved in the transcriptional cascade driving molting initiated by the steroid hormone, ecdysone. Based on its position in the molting cascade and that sterol-derived molecules are ligands for its mammalian ortholog (ROR), NHR-23 is the best candidate to be regulated by a molting hormone. Our study of how NHR-23 expression oscillates, and how it promotes oscillatory gene expression also provides an opportunity to understand how diet impacts developmental processes. NHR-23 has been implicated in diet-induced developmental acceleration; thus, our work will provide insight into how metabolites control gene expression to modulate physiology and development.
Molting also involves nematode-specific molecules and regulatory mechanisms, which offer potential intervention points to treat parasitic nematodes. Parasitic nematodes are an understudied global health burden. It is estimated that 2.9 billion people are infected with parasitic nematodes worldwide, comprising 85% of neglected tropical disease. These parasites depress human health, cognition, and productivity, and increase the severity of other common diseases caused by viruses and bacterial pathogens, including HIV, malaria, and tuberculosis. Nematodes also parasitize crops and livestock, causing huge losses in production. Few drugs exist for treatment of parasitic nematode infections, and the widespread emergence of nematode resistance to these few drugs highlights the need for novel therapeutic interventions. Parasitic nematode infections are a global burden, infecting much of the developing world. Billions of dollars of lost economic productivity is caused by these infections, keeping afflicted countries mired in a cycle of poverty. Molting has been highlighted as a target for control of both arthropods and nematodes.
Projects in the lab focus on how key developmental regulators such as NHR-23 and LIN-42 oscillate during each larval stage and how they control downstream target genes to coordinate molting and stage-specific developmental events. Another project focuses on how NHR-23-regulated proteases and protease inhibitors are coordinated to remodel the aECM during each larval stage. We are also exploring whether a ligand regulates molting. Our data and those of others suggest that NHR-23 likely sits as the top of a hierarchy of transcriptional regulation for molting. Moreover, its insect ortholog is involved in the transcriptional cascade driving molting initiated by the steroid hormone, ecdysone. Based on its position in the molting cascade and that sterol-derived molecules are ligands for its mammalian ortholog (ROR), NHR-23 is the best candidate to be regulated by a molting hormone. Our study of how NHR-23 expression oscillates, and how it promotes oscillatory gene expression also provides an opportunity to understand how diet impacts developmental processes. NHR-23 has been implicated in diet-induced developmental acceleration; thus, our work will provide insight into how metabolites control gene expression to modulate physiology and development.
Molting also involves nematode-specific molecules and regulatory mechanisms, which offer potential intervention points to treat parasitic nematodes. Parasitic nematodes are an understudied global health burden. It is estimated that 2.9 billion people are infected with parasitic nematodes worldwide, comprising 85% of neglected tropical disease. These parasites depress human health, cognition, and productivity, and increase the severity of other common diseases caused by viruses and bacterial pathogens, including HIV, malaria, and tuberculosis. Nematodes also parasitize crops and livestock, causing huge losses in production. Few drugs exist for treatment of parasitic nematode infections, and the widespread emergence of nematode resistance to these few drugs highlights the need for novel therapeutic interventions. Parasitic nematode infections are a global burden, infecting much of the developing world. Billions of dollars of lost economic productivity is caused by these infections, keeping afflicted countries mired in a cycle of poverty. Molting has been highlighted as a target for control of both arthropods and nematodes.