Pew Charitable Trust Award

The Simunovic lab will explore how an interplay of mechanical forces and gene regulatory networks guides embryo implantation. In the first days of embryonic development, a uniform ball of cells will begin to form tissues, including those that will give rise to the placenta. Cell fate choices are typically governed by biochemical signals; however, it is much less understood that they may also be influenced by mechanical cues such as those coming from the uterine wall. Studying early mammalian development comes with a critical challenge—implantation obscures the embryo from view, preventing us from gaining molecular details about it. To overcome this challenge, we recently developed an approach that uses pluripotent stem cells and three-dimensional tissue culture to model the early embryo, similar to how organoids model organ development. Now, using cutting-edge techniques in synthetic and stem cell biology, biophysics, and imaging, I will establish how mechanical perturbations activate the genes and signaling networks that transform embryonic architecture to establish the body plan. I will leverage our organoid models to study the molecular and biomechanical mechanisms underlying implantation. My work will open a window on some of the earliest and most critical events in our own development and provide insights that could hopefully lead to new strategies for treating conditions in which implantation is impaired, including infertility, miscarriage, and many pregnancy disorders.