ERC Consolidator Grant for Andrea Pauli to study fertilisation
Fertilisation marks the beginning of life of any sexually reproducing organism. However, the molecular machinery and biophysical mechanisms underlying sperm-egg recognition and fusion remain largely unclear. The European Research Council (ERC) has now awarded Andrea Pauli a prestigious Consolidator Grant to shed light on the twilight of sexual reproduction.
The physicist Richard Feynman famously stated: “what I cannot build, I do not understand”. In line with this quote, Andrea Pauli and her lab at the IMP link developmental biology with biochemistry to pursue a vision of reconstituting a “fertilisation interface” in vitro.
To do so, the scientists first need to acquire a detailed understanding of the molecular mechanisms which underly fertilisation. However, for a process as fundamental and widespread as this, the molecular processes that steer fertilisation are rather poorly understood. In particular, the molecular mechanism of sperm-egg fusion has remained elusive in all vertebrates.
For the next five years, a consolidator grant of the European Research Council (ERC) will support Andrea Pauli’s research of fertilisation along two avenues: sperm-egg recognition and fusion. The work will build on the Pauli lab’s ground-breaking discovery of the egg protein Bouncer as a crucial factor for sperm-egg recognition in fish. In addition, the lab more recently identified zebrafish sperm factors, namely Dcst1/2 and Spaca6, which are conserved in mammals and indispensable for fertilization in vertebrates. However, it is unclear how any of these factors function in fish or mammals, and how they work together to mediate sperm-egg binding and fusion. Moreover, additional fertility factors probably participate in mediating sperm-egg fusion and remain to be identified.
To uncover the elusive mechanism of vertebrate fertilization, the lab is planning to use both, candidate approaches with known fertility factors such as Bouncer and Dcst1/2 as entry points, as well as unbiased genetic screens. The lab will combine functional studies and in vitro experiments. Through this, Andrea Pauli hopes to identify unknown fertility factors, work out the role of both known and novel factors in the molecular fertilisation machinery, and ultimately reconstitute fertilisation in vitro.
“Addressing the knowledge gap in fertilisation will have an immediate impact on the field of reproductive biology,” says Andrea Pauli. “I hope our findings will advance new concepts also for other fields involving cell-recognition and -fusion mechanisms, including immunology, neurobiology, host-pathogen interactions, membrane dynamics, and signalling.”
ERC Grants are the EU’s principal funding tool for basic research and are awarded since 2007. The grants have developed into one of the most highly regarded marks of distinction for scientists in participating countries. ERC Grants are highly competitive with an application success rate of only 13 percent. Applications from IMP scientists in the period of 2014 to 2020 have yielded a success rate of 56 percent, placing it among the most competitive institutions eligible. Currently, 11 out of 15 faculty members at the IMP have been awarded at least one ERC grant.