Since the discovery over half a century ago that egg cells can reprogram not only sperm but also nuclei from other cells into a state of totipotency, the identities and mechanisms of reprogramming factors have been a mystery. Our research focuses on how chromatin is reprogrammed to totipotency. Totipotency is the developmental potential to generate all cell types and a new organism. Our mission is to identify the mammalian reprogramming factors and study their functions and mechanisms using embryology, genomics, biochemistry and structural biology. Our laboratory recently identified a pioneer transcription factor that "awakens" the genome in totipotent mouse embryos. We would like to better to understand the mechanisms of how this and other newly identified reprogramming factors interact with nucleosomes and reprogram chromatin to totipotency. 

The project on offer is to study novel reprogramming factors using biochemical assays and cryo-EM structure determination, with the possibility to combine the research with single-molecule imaging or in vivo studies.

Useful reading: 

1. Gassler et al. Zygotic genome activation by the totipotency pioneer factor Nr5a2. Science 2022.
2. Kobayashi et al. Nucleosome-bound NR5A2 structure reveals pioneer factor mechanism by DNA minor groove anchor competition. Nat Struct Mol Biol 2024.
3. Kravchenko & Tachbana. Rise and SINE: roles of transcription factors and retrotransposons in zygotic genome activation. Nat Rev Mol Cell Biol 2025.
4. Dequeker et al. MCM complexes are barriers that restrict cohesin-mediated loop extrusion. Nature 2022.