Spermatogenesis [more] is a complex developmental pathway that involves hormonal signaling, cell-cell interactions and cell migration. Genetic experiments have identified many conserved genes essential for progression through meiosis and gametogenesis notably in model organisms such yeast, worm, fly and mouse. A better understanding of transcriptional regulatory events and epigenetic mechanisms controlling progression through germ cell development should help identify (epi)genetic causes of unexplained male infertility [more]. Numerous transcripts are present at high concentrations in testicular cells and some of them – encoded by Cancer/Testis genes [more] – accumulate in somatic non-testicular cancers. CT genes are targets for cancer immunotherapies and may contribute to the onset and progression of somatic malign tumors. 5-Fluorouracil [more] is a widely used anti-cancer drug that inhibits the exoribonuclease EXOSC10. A better understanding of 5-FU’s mechanism of action and the underlying causes of cancer cell resistance against the drug will likely improve the outcome of chemotherapy.
Mammalian biology of reproduction: to gain insight into regulatory mechanisms controlling male meiosis and gametogenesis we investigate genome-wide transcription during sex differentiation and spermatogenesis in rodents and healthy humans as well as in infertile patients. More recently, we have started to identify testicular long noncoding RNAs (lncRNAs) and to study the role of the exosome component Rrp6/EXOSC10 in mammalian male gonads. Key questions we address are how germline-specific genes are transcriptionally regulated, and what roles genes that are highly (and often specifically) induced in germ cells play in spermatogenesis and fertility. F. Petit and S. Jamin use mammalian cell lines and Cre-lox recombination in mice to gain insight into the reproductive functions of a member of the nuclear receptor superfamily, and of different factors involved in the AMH (anti-Müllerian hormone) signaling pathway. F. Smagulova is interested in epigenetic control mechanisms governing mouse meiosis and gametogenesis and how external factors such as pesticides influence them.
Molecular mechanisms of cancer progression: we integrate whole-genome expression data from testicular samples and a large number of somatic cancers and their corresponding healthy tissues to identify and to functionally characterize novel Cancer/Testis genes. Specifically, we seek to understand if and how certain Cancer/Testis genes contribute to the etiology and the progression of various somatic cancers. In a new line of investigation we study the question if the chemotherapeutical agent 5-Fluorouracil inhibits cells growth via de-regulation of lncRNAs, which are targeted by Rrp6/EXOSC10. We use mouse and yeast model organisms to determine the genome-wide RNA profiles of 5-FU treated versus exoribonuclease-deficient strains.
Gametogenesis in S. cerevisiae: we are interested in factors controlling meiotic progression via transcriptional regulation in yeast. To this end, we identify and characterize novel protein-coding genes, developmentally regulated transcript isoforms, non-coding RNAs and an exosome component important for the process. We have recently begun to integrate yeast transcriptome, proteome and interactome data to ultimately establish a molecular systems biological view of meiosis and gametogenesis in this simple eukaryote.