BME PhD Preliminary Exam Announcement for Nissa J. Larson (D. Umulis, advisor) Everyone is invited to attend the public presentation beginning at 3:00 PM. Title: Signal processing and robustness of the BMP network during zebrafish embryogenesis and dorsoventral patterning Date: May 8th Time: 3:00 PM Location: MJIS 1001 Committee Members: Drs. David M. Umulis (Major Professor), Elsje Pienaar, Qing Deng, & Adrian Buganza Tepole Abstract: In developing tissues, signal transduction from morphogen gradients conveys positional information to cells, resulting in cell differentiation. One such morphogen is bone morphogenetic protein (BMP), of the TGF-β superfamily, whose network is highly conserved across many species. In Danio rerio (zebrafish), this signaling pathway directs dorsoventral axis formation during early embryogenesis. The feedback loops among the molecular species involved are extremely complex, and the requirement for the heterodimer-heterotetramer complex for signal transduction is theorized to be due to functional advantage but no evolutionary drivers have been uncovered. Building and developing a multiscale model of this process will allow us to mechanistically assess zebrafish phenotype variability related to the distributions of noise and stochasticity. We can also analyze time-dependent signaling and frequency metrics that are not available in deterministic modeling. Fast Fourier Transform and cumulative energy spectral density show that the heterodimer-heterotetramer complex may function as a low-pass filter in dorsal-ventral axis formation, specifically tuned to the noise of the system. To further probe this system, we are working to develop an experimental optogenetics protocol to genetically manipulate dorsoventral signal transduction in vivo and analyze fluorescence intensity of the downstream pSmad gradient. Through these multiscale modeling efforts and experimental coupling, we hope to further understand the noise origins and signal processing of this network. As the BMP signaling pathway has been implicated in human bone growth and wound healing, its study in simpler systems stands to accelerate our comprehension of BMP network and molecular mechanisms with application in regenerative medical studies. -- Bmeroundtable-list mailing list Bmeroundtable-list@ecn.purdue.edu https://engineering.purdue.edu/ECN/mailman/listinfo/bmeroundtable-list