Identifying and studying small molecules that inhibit meiotic development and fertility in eukaryotic organisms

Meiosis is a key developmental process that occurs in all eukaryotes, which engage in sexual reproduction. This includes unicellular organisms, such as the budding yeast Saccharomyces cerevisiae. During meiosis a competent diploid cell replicates its DNA once and then undergoes two consecutive divisions followed by morphogenetic differentiation events, collectively termed gametogenesis (commonly referred to as sporulation in budding yeast). Meiosis in yeast and spermatogenesis in higher eukaryotes are analogous developmental pathways and mechanisms governing meiotic development have been extensively studied over the last few decades in many different model organisms. However, the question how synthetic and bioactive chemical compounds influence meiosis and gametogenesis has not been addressed in a general fashion so far.
The aims of this project are the identification of drugs that inhibit these processes in budding yeast, and the discovery of their corresponding drug targets using various high-throughput screening assays. This research has broad implications for understanding the impact of drugs (some of which have or will have a pharmaceutical application) on meiosis and gametogenesis and therefore on fertility in eukaryotic organisms. Furthermore it has strong potential for identifying chemical substrates that inhibit gene products essential for meiosis and that can therefore be used as rapid and in some cases reversible laboratory tools to study the processes.


Ulrich Schlecht