To achieve accurate packaging of DNA into chromatin, cells need to precisely control the concentration of histone proteins, the building blocks of nucleosomes. Typically, histone production is tightly linked to DNA replication during S-phase, to ensure that histones are produced when needed. However, at this point we do not know when this cell-cycle-dependence of histone production is established in the early mammalian embryo, nor how embryos are able to produce the right amount of histones despite exponentially increasing DNA concentration during the early stages of development.
We will use molecular biology and imaging approaches to obtain a quantitative understanding of histone biogenesis during early mouse development. Manipulation of the embryo will then be used to disentangle the mechanistic contribution of DNA content, developmental stage, and cell size.
K.M. Schmoller and J.M. Skotheim (2015), The Biosynthetic Basis of Cell Size Control. Trends in Cell Biology, 25, 793-802
This interdisciplinary project will be a close collaboration with the group of Prof. Dr. Maria Elena Torres-Padilla (Epigenetics and cell-fate in early mammalian development) and requires the candidate to perform experiments in both labs.