Forward Genetics Identifies a Requirement for the Izumo-like Immunoglobulin Superfamily spe-45 Gene in Caenorhabditis elegans Fertilization

Fertilization is a conserved process in all sexually reproducing organisms whereby sperm bind and fuse with oocytes. Despite the importance of sperm-oocyte interactions in fertilization, the molecular underpinnings of this process are still not well understood. The only cognate ligand-receptor pair identified in the context of fertilization is sperm-surface Izumo and egg-surface Juno in the mouse [1]. Here we describe a genetic screening strategy to isolate fertilization mutants in Caenorhabditis elegans in order to generate a more complete inventory of molecules required for gamete interactions. From this screening strategy, we identified, cloned, and characterized spe-45, a gene that encodes an Izumo-like immunoglobulin superfamily protein. Mammalian Izumo is required for male fertility and has the same basic mutant phenotype as spe-45. Worms lacking spe-45 function produce morphologically normal and motile sperm that cannot fuse with oocytes despite direct contact in the reproductive tract. The power of this screen to identify proteins with ancient sperm functions suggests that characterization of additional mutants from our screen may reveal other deeply conserved components in fertility pathways and complement studies in other organisms

Trending Advancements in Technologies Pertinent to Therapeutical Pharmacodynamics

It is omniscient that pharmacodynamics of a drug is understood as its effect on body by interacting with the structure of targets to either activate or inhibit their function/action. Based on the activity of the drug to the target binding site they have been classified into different types. Physiological, cellular, molecular, biochemical, and toxicological effects individually have a significant role in drug’s effect and response. The mechanism of action, dosage and its response, therapeutic index are some of the noteworthy parameters to be considered in drug pharmacodynamics. This chapter comprehends the above-mentioned concepts, their importance in pharmacodynamics of drug, and the impact of recently developed methods like genome-wide or transcriptome-wide sequencing, chronopharmacodynamics, systems biology, pharmacometabolomics, etc., in different stages of drug discovery process, and how the digitization of therapeutics and healthcare direct the path to personalized medicine. The integration of bioinformatics, systems biology, and big data related approaches like ML & AI with the pharmacological (PK/PD) study highly benefits the patients’ therapeutics