Chad Glen

PhD Thesis Defense

Date: Wednesday July 25, 2018 at 1pm 

Location: CHOA Seminar Room 1005, EBB-Krone 

Advisors:

Dr. Melissa Kemp

Dr. Todd McDevitt

Committee Members:

Dr. Michael Levin

Dr. Krishnendu Roy

Dr. Brani Vidakovic 

Dr. Eberhard Voit

Title: Investigating the role of intercellular communication on spatial differentiation through agent-based modeling.

Abstract: 

Gap junction communication within multicellular systems produces complex networks of intercellular connectivity that result in heterogeneous distributions of intracellular signaling molecules. In this work, we investigated the emergent systems-level behavior of the intercellular network within embryonic stem cell (ESC) populations and the corresponding spatial organization of colonies during early neural differentiation. Using experimentally-derived parameters, an agent-based model was able to recapitulate and predict spatiotemporal trajectories of differentiation using molecular transport through gap junctions as the differentiation mechanism. This mode of intercellular communication as a driver of differentiation was validated with small molecule inhibitors as well as CRISPR interfence targeting of connexins. In addition, we developed a graphical user interface for generating agent-based models containing various modes of communication. This platform provides a tool to interrogate the spatial aspects of information transfer within multicellular systems and facilitates accelerated design of engineered living systems such as organoids by enabling the analysis of multiscale communication within cell populations of any morphology or organization.