Combining X-rays and electrons to shed light on fertilization and antibacterial defense

In all sexually reproducing organisms, the life of a new individual begins with the interaction between egg and sperm at fertilization.

In humans and other mammals, this fundamental encounter requires two species-restricted recognition events that occur at the level of the egg coat and plasma membrane.

Building on the knowledge that we gained from determining structures of isolated gamete recognition proteins and, more recently, the first 3D structure of an invertebrate egg coat/sperm protein complex (Raj et al.

Cell 2017), we will now take advantage of the “resolution revolution” in cryo-electron microscopy to start addressing structural aspects of fertilization at higher levels of organization.

Specifically, we will complement our crystallographic studies with single particle/helical reconstruction studies of egg coat filaments, as well as investigate egg coat and plasma membrane fertilization events by focused ion beam milling coupled to cryo-electron tomography.

In parallel, we will broaden the scope of this work by both addressing evolutionary aspects of gamete interaction, as well as studying structurally related filaments of a key human urinary protein that acts as decoy for uropathogenic bacteria.

These studies will major implications for understanding human infertility and informing the development of non-hormonal contraceptives, as well as for fighting urinary tract infections - the most common type of non-epidemic bacterial infection in humans.