The life of every sexually reproducing being starts with the fusion of sperm and egg, a process called fertilization. For fertilization to occur, compatible gametes must recognize each other, bind to each other, and eventually fuse for form a new cell, the zygote that gives rise to a new embryo. Despite of its central position at the beginning of each organism’s life, the mechanisms underlying fertilization in vertebrates have remained mysterious.
Although a handful of factors have been identified to be essential for gamete interactions in mice, their precise roles and mechanisms are unclear, and they are insufficient to mediate gamete fusion. From other fusion contexts, e.g. viral-cell fusion, it is known that specialized proteins called fusogens facilitate fusion by remodeling membranes and orchestrating membrane fusion. However, no fusogen-like protein mimicking known viral fusogens has been found in vertebrate gametes, and none of the known vertebrate fertility factors share similarities with known viral fusogens, leaving the nature and mechanism of sperm-egg fusion in vertebrates completely unclear.
In this project we aim to uncover the mechanistic principles of vertebrate fertilization. What are the molecules on the surface of sperm and egg that are required for sperm-egg interaction, and how do these factors work together to enable sperm-egg fusion?
To address these questions, we will focus on the two key phases of fertilization, sperm-egg recognition & binding, and sperm-egg fusion, using two complementary approaches: On the one hand, we will take advantages of zebrafish as a vertebrate model with external fertilization for in vivo analyses. On the other hand, we will employ in vitro approaches to investigate the protein structure and complex formation of fertilization factors.
Overall, our goal is to mechanistically understand how sperm and egg recognize and bind to each other, and how their membranes subsequently fuse. The insights gained will form the basis for our ultimate vision, to ‘re-build’ the vertebrate fertilization interface in vitro, and by these means understand one of the most fundamental processes of life.
Due to the scarcity of mechanistic knowledge, our research will provide major conceptual and technological advances to the field of fertilization by elucidating the nature of the elusive sperm-egg recognition and fusogenic machinery in vertebrates and by providing mechanistic insights into the physiological role of known and novel factors. We anticipate that our findings will also impact other fields involving cell recognition and fusion mechanisms, including immunology, neurobiology, host-pathogen interactions, membrane dynamics, and signaling.
