The research goals of the Pinello lab are to understand the conserved cellular and molecular mechanisms responsible for gamete membrane fusion during fertilization. Despite their importance to the continuation of eukaryotic life on earth, the proteins controlling fusion of two specialized gamete cells like sperm and egg to create a single zygote are not yet well understood in many organisms, including humans and even other historically more well-studied model systems, like sea urchin, mouse, nematodes, and yeast. In the past years, however, breakthrough studies in flowering plants, the malaria parasite, Plasmodium, the ciliate Tetrahymena, and the green alga Chlamydomonas have identified HAP2, an ancient protein required for gamete membrane fusion across eukaryotic kingdoms. Interestingly, HAP2 is structurally analogous to the membrane fusion proteins that viruses like Dengue and Zika use to enter host cells during infection, suggesting that it may initiate cellcell fusion via a similar mechanistic pathway. By employing a variety of biochemical, functional, and molecular genetic approaches, we use the unicellular organisms Chlamydomonas and Tetrahymena to identify the key proteins and conserved molecular events driving the essential step of HAP2-mediated gamete fusion during eukaryotic fertilization. We envision applying our fundamental molecular discoveries in fertility to develop transmission-blocking vaccines for parasitic diseases like malaria, as well as to help generate novel strategies to block the sexual reproduction of invasive weed species and agriculturally important insect pests.
