“Work in our brand new laboratory is geared towards understanding the mechanisms that prevent aneuploidy in mammalian eggs and embryos.”
Research in the lab is mainly propelled by our recent finding that actin prevents chromosome mis-segregation and aneuploidy in mouse eggs (Figures 1 and 2) (Mogessie and Schuh, Science, 2017).
Figure 1. Actin prevents lagging chromosomes in mouse oocytes. At anaphase I, homologous chromosomes are separated and partitioned between the egg and the polar body. In contrast, in a significant majority of oocytes that lack actin, chromosomes fall behind during segregation (lagging chromosomes, shown in magnified views in bottom panel).
Figure 2. Model for the function of actin in protecting eggs against aneuploidy. Bundling of microtubules into functional k-fibers by actin promotes correct alignment of chromosomes in metaphase and their accurate segregation during anaphase. Disruption of actin compromises k-fibers and leads to chromosome alignment and segregation defects, and subsequently to aneuploidy.
A key question we are currently tackling is how actin filaments interact in a dynamic and temporally-regulated manner with spindle microtubules to orchestrate accurate chromosome segregation in mammalian oocytes. In order to identify the Spindle Actin Assembly Proteins (SAAPs) that mediate this cytoskeletal crosstalk, we are combining proteomics, genetic loss-of-function and rapid protein depletion assays with high resolution live imaging of meiosis. Ultimately, we aim to build a cell-free, meiosis-like cytoskeletal crosstalk system using knowledge obtained from our cell biology experiments. This in vitro reconstitution assay will enable us to obtain direct mechanistic understanding of SAAP function and the cellular regulatory mechanisms involved and spindle actin assembly and organisation.
Knowledge gained from this and other research projects in the lab has the potential to be used in assisted human reproduction. To ensure maximum impact of our work, we will ultimately collaborate with clinicians to translate our research findings into infertility treatments and prevention of human diseases that arise from chromosomal abnormalities in early stage embryos.