Finding the molecular basis of the beginning of life
The first step in mammalian fertilization is recognition between proteins in the extracellular coat of the egg and sperm. Luca Jovine runs a research group dedicated to gain a better understanding of the molecular basis of this first
step of life. The goal is to visualize fertilization at the molecular level and the main tool is structural biology. The group has already been able to describe the 3D structure of an important part of a sperm receptor protein in the matrix of the egg cell.
Luca Jovine established his research group at The Department for Biosciences and Nutrition in 2005. The first goal for him and his colleagues was to solve the three-dimensional structure of a certain protein fragment that is common to all the proteins that make up the thick matrix surrounding mammalian eggs. Just three years later they could publish the structure, determined by X-ray crystallography, in the prominent scientific journal Nature. Thereby they became the first researchers in the world to report the atomic architecture of a conserved vertebrate protein essential for fertilization.
"We reached this result faster than I had expected, which of course was encouraging. But we are still at the beginning of our work," says Luca Jovine, who recently was nominated EMBO Young Investigator.
The egg and its matrix
Mammalian eggs are surrounded by a thick, extracellular matrix called zona pellucida, ZP. This matrix plays essential roles in the growth of egg cells, fertilization and the processes that take place between fertilization and implantation in the womb. Depending on the species, the matrix contains three or four proteins, called ZP 1-4. The structure described by Luca Jovine and his group is a part of the sperm receptor protein of mice, ZP3. Multiple copies of the same part, which has been named ZP-N, are also present in the other ZP components. As a result, ZP-N plays important roles not only in the species-specific recognition between egg and sperm, but also in ensuring that only a single sperm fuses with the egg.
For our knowledge about fertilization and evolution it is important to learn more about the very first step of mammalian life. At the same time, although their current work is purely basic research, Luca Jovine and his group hope that these results might also lead to new medical treatments in the future.
"Hopefully we will be able to contribute to a better understanding of the causes of infertility. And a likely application could be the development of new, non-hormonal contraceptives," he says.
A major future challenge will be to identify and visualize crucial parts of the protein complexes formed by egg and sperm at the moment of fertilization.
Text: Helene Wallskär