"Design principles and control in biological systems"

 

 

 

My research aims to understand how cellular systems organize themselves. This work spans multiple scales from a single cell (e.g. cell polarity and cell division), to multicellular systems (e.g. the early embryo and the intestinal crypt), to the dynamics of tissues (e.g. development and regeneration in the central nervous system). In this talk, I will focus on two aspects of this work. First, I will discuss the induction of intra-cellular polarity in the context of motility. Substantial efforts have been directed at mapping the signal transduction networks that direct polarity responses. These networks are however very complex and difficult to interpret. Here I will describe new, highly efficient and automatable computational techniques that can be used to elucidate 1) how these networks process stimuli and 2) how they can be augmented to manipulate cells sensitivity to their environment. I will additionally discuss ongoing work with the Levchenko Lab (Yale Bioengineering) aimed at understanding how changes in polarity machinery influence cellular behaviors, and in particular, how this might lead to dysregulation of motility in cancer cells.

 

Second, I will discuss how the early mammalian embryo accomplishes the critical first step in its development, formation of the precursor to the placenta. While numerous investigations have posited mechanisms for constructing of these structures, it remains unknown how they are reproducibly and robustly organized. In collaboration with the Cho Lab (Dev. and Cell Biology at UC Irvine), we combine modeling with immunofluorescence image quantification to investigate this process in developing mouse embryos. The outcomes of this work are three fold: 1) the process of cell fate specification is gradual rather than switch like, creating a time window during which cells maintain plasticity, 2) gene expression noise (at endogenously observed levels) has an important positive role in maintaining organization of embryonic structures, and 3) in addition to regulating transcriptional expression levels, cells may regulate noise levels to confer this benefit.