Dissecting the role of transcription in meiotic DNA double-strand breaks patterning

Meiosis is a specialized cell division process for producing gametes, and meiotic defects frequently cause infertility or birth defects (e.g. Down syndrome).

Successful meiosis is ensured by the induction of hundreds of DNA double-strand breaks (DSBs) at the correct chromatin sites.

The pattern of DSBs is suggested to be controlled by some special chromatin features that are established upon transcription.

However, as transcription is essential for life, it is difficult to directly study whether and how transcription influences DSB patterning during meiosis in common model organisms.The unicellular protist Tetrahymena thermophila has two nuclei and, importantly, transcription can be shut off in the meiotic nucleus without affecting meiotic progression.

Therefore, the DIRECT-DSB project was designed to overcome the intrinsic limitations of other model systems by investigating the impact of transcription on DSB patterning in Tetrahymena.Through in-depth collaborations with the host supervisor, who has a profound knowledge of chromatin biology, and with other leading researchers with expertise in meiosis, I will first characterize and compare DSB patterns and chromatin features in the presence and absence of transcription and then study potential correlations between DSB pattern alterations and transcription-induced chromatin alterations.

The successful accomplishment of the project will (i) clarify the relationship between transcription and DSB patterning, which has been a much-debated topic in the meiosis field for many years; (ii) deepen our understanding of meiosis, which, in the longer term, may contribute to solving the problem of increasing infertility rates in the European Union and elsewhere; (iii) enable knowledge exchange and dissemination, and the establishment of novel methods; and (iv) help me to develop into a leading independent scholar by improving my research proficiency and transferable skills.