Dr. Xue Mei joined the Department of Biolocial Sciences at St. John’s in the fall of 2022. She is a broadly trained developmental biologist and geneticist. Prior to St. John’s, she studied fertilization as a postdoctoral researcher in Dr. Andrew Singson’s lab at Rutgers University.
Fertilization is an essential process in sexual reproduction. During fertilization, two haploid gametes, the sperm and the egg, come together and fuse to form a zygote. The zygote then goes through a series of transitions to activate embryogenesis. Studying fertilization helps us understand fertility and infertility, and may allow us to develop innovative ways of contraception. Studying how the gametes interact also contributes to our understanding about basic biology of how cells interact and fuse.
When the sperm and egg meet, they recognize and bind each other, and eventually fuse. The molecular basis of how they interact is still an open question. Recent years of research has identified a handful of proteins on the surface of the sperm or egg that are essential for sperm-egg interactions (Figure 1A). However, not much is known about how these proteins might work together. Research also suggests that additional unknown molecules are involved.
Figure 1. Fertilization molecules at the interface between the sperm and egg. A, molecules in mammals. B, molecules in the worm.
The nematode Caenorhabditis elegans has been a pioneering model in fertilization research. The worm has transparent body, relatively short life cycle, and is amenable to a wide variety of genetic manipulations. One of the ways of discovering genes that regulate a biological process is mutant screening (also called a forward genetic screening). By introducing random mutations into the genome, one can look for the phenotypes of interest – as a result of a disruption in the biological process. Identifying the genes with causative mutations for the phenotype would then point to a role for those genes in regulating the related process. Using mutant screening, researchers have isolated many fertility mutants. Interestingly, they found a class of mutants in which the sperm seems to develop and behave normally but fails to fertilize the egg. Later work identified a class of genes that encode sperm surface proteins that are thought to mediate the interaction between the sperm and egg (Figure 1B). This class is referred to as the spe-9 class.
Current research in my lab will focus on the following three aspects:
Dissecting molecular interactions among SPE-9 class of proteins using genetic and biochemical approaches.
Characterizing mutants from the mutant screening that showed interesting fertility phenotypes.
Identify additional fertilization molecules with a focus on those on the egg surface, using a reverse genetic approach (candidate gene approach).