The aphrodisiac gut: defining the factors promoting yeast mating within insect intestines

Saccharomyces cerevisiae (Sce) has seen widespread use by humans throughout history for winemaking, brewing, and bakery. However, a process fundamental for this yeast’s evolution still remains only partially understood: interstrain mating (outbreeding), which potentially results in strains bearing new genomic settings and fitness. While outbreeding is easily achievable in laboratory settings, it is extremely rare in nature. In fact, we have only recently discovered the first environment where it can occur: within wasp guts. Comprehending what makes the insect gut an environment suitable for Sce mating would provide us with a better understanding of Sce evolution and expand our knowledge beyond the unnatural lab settings. Outbreeding is achieved through a multi-step process encompassing sporulation, germination, ascus break, and mates encounter. These steps may be promoted within wasp guts thanks to the sequence of drastically different chemical and mechanical stresses peculiar to this environment. We have set up a team of experts in all the fields necessary to tackle this hypothesis: microbiology, genetics, chemistry, physics, and computational biology. We will carry out in vivo experiments to assess the wasp gut environment by using dedicated sensors and Sce genes fundamental for germination and sporulation in this environment. These data will be instrumental to develop a genome-scale mathematical model exploring yeast genetics, metabolic and environmental features favoring germination and sporulation. In vitro high-throughput assays assessing both the yeast response and metabolites measured by dedicated intra- and extra-cellular sensors will provide further data to calibrate the model. Physical forces required for Sce ascus break or mate encounter will be measured through up-to-date biophysical techniques: cylindrical Couette chambers, micropipette force sensors, and microfluidic droplets. We will bring together the information that we gather about each stage to develop microfluidic devices emulating the structure and physiology of wasp guts and investigate there the entire process leading to outbreeding. This project will unveil the key factors of Sce evolution by providing fundamental insights on the biological mechanisms leading to outbreeding in natural settings, thus potentially revolutionizing our current understanding of the process.