Ovarian cancer (OC) is the most lethal gynecological malignancy, and the most common and malignant subtype is high-grade serous ovarian cancer (HGSOC), which arises from fallopian tube (FT) epithelium, and is often detected too late. Human microbiome is a community of trillions of microorganisms that inhabit body, and their symbiosis with organism is crucial for maintaining homeostasis, while dysbiosis can cause cancer. Relationship between microbiome and OC is not yet fully elucidated, especially not at the level of intratumoral microbiome (oncobiome). However, it was shown that gut microbiome dysbiosis in mice causes OC progression by activating Hedgehog pathway (HHP). We showed that expression of transcription factors GLI, the main HHP effectors, was decreased in HGSOC. Further, we discovered that some genes related to innate immunity are GLI target genes. Since innate immunity plays a critical role in protection against bacteria, we hypothesize that oncobiome, by downregulating HHP, debilitates innate immunity and thus enhances HGSOC development. This project aims to investigate the interaction between the HHP and oncobiome in HGSOC. In fresh HGSOC and healthy FT tissue bacterial composition will be determined by whole 16S rRNA seq, human and bacteria transcriptome determined by dual RNA-seq will show which bacterial genes are expressed and which human genes may be altered due to infection, while metabolomics will show which bacterial metabolites could cause malignant transformation of FT cells. In stool and vaginal swabs, bacteria presence will be tested, to develop non-invasive diagnostic tests. In archival HGSOC tissue, bacterial presence and protein levels of genes affected by bacteria will be determined, to discover new prognostic biomarkers. Finally, by co-culturing FT cells with bacteria we will elucidate molecular mechanisms and cellular effects. Association between oncobiome, HHP and HGSOC opens new possibilities for early detection and therapies.