A cell from an adult mouse can be chemically persuaded to revert to an embryo-like state, and this project aims to pin down exactly how that happens. The process, called induced pluripotency, lets scientists turn skin or blood cells into stem cells that can become any tissue in the body. But the molecular steps are still poorly understood, and the conversion is inefficient and unpredictable. This research will map the precise sequence of events—focusing on the protein Nanog and the culture environment—that drives a mature cell to adopt a naive, flexible identity. The team will also test whether the same mechanisms occur naturally in early embryos, which could reveal whether reprogramming mimics normal development. Because this is fundamental science, there is no immediate practical application. However, a complete mechanistic understanding could eventually make reprogramming faster, safer, and more reliable. That would open the door to patient-specific cell therapies for degenerative diseases, drug screening on human cells, and a deeper grasp of how cells commit to their fates in the first place.
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My research has centred on nuclear reprogramming since my PhD. As an independent Principal Investigator I have developed unique systems to better investigate the process of induced pluripotency. This resulted in the identification of Nanog and culture environment as key players and has helped re-define our understanding of the biological roles of Oct4. As a senior principal investigator I want to build on this platform and on exciting new findings from my lab. Specifically, I will focus on mecha nisms of induced pluripotency and on parallels with in vivo phenomena. 1-Define mechanistically the cell state transition leading to the acquisition of a naive pluripotent cell state. New data from our lab shows that Nanog and culture environment work synergistically on reprogramming mechanisms. We also found that depending on the culture environment, defined ES-level of Oct4 expression instructs either a naive pluripotent cell state or cell differentiation. My aim is to further explore t he relationships between key players and understand how the observed reprogramming mechanisms are regulated. I also want to fully define the direct molecular reprogramming mechanism of Nanog by investigating how its interactions with co-factors, mostly epigenetic regulators, affect its capacity to reprogram. 2-Investigate parallels between mechanisms of reprogramming and analogous biological processes. We were the first to draw a parallel between induced pluripotency and embryonic developm ent. Our future aim is to investigate how general is this concept by assessing if identified nuclear reprogramming mechanisms are recapitulated during the acquisition of the naive epiblast in the early embryo.
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