Research interest: quantitative analysis of development
The main focus of our laboratory is on the quantitative analysis of development. Our goal is to establish truly predictive and multiscale models that connect multiple levels of description, from gene sequence to pattern formation and morphogenesis. We emphasize close coupling between experiments, computations, and theory, and use Drosophila as an experimental system for model validation. Current projects include genome-wide experimental analysis of signal integration in the Drosophila ovary, computational prediction of sequence-specific patterns of gene regulation by multiple extracellular signals, parameter estimation for morphogen gradients, and quantitative analysis of feedback control in pattern formation.Signaling crosstalk in the drosophila ovary:
The dorsoventral patterning of the follicular epithelium in the developing Drosophila egg relies on the joint activity of evolutionarily conserved EGF and BMP signaling pathways. We have carried out a genome-wide screen for common targets of EGF and BMP pathways in the ovary, established the spatial patterns of their expression, and begun to probe the mechanisms for their transcriptional and posttranscriptional regulation. The current challenge is to go beyond simple association of extracellular signals and transcriptional targets and to understand how the spatial patterns of identified genes are established by integration of two extracellular signals.Quantitative analysis of morphogen gradients:
Pattern formation in development depends on quantitative control of the spatial ranges of secreted ligands. At this time, direct measurements of the length scales of morphogen ligands are extremely difficult. We have developed a parameter estimation approach for quantifying the spatial range of Gurken, an EGF-like ligand that acts as a morphogen in patterning of the Drosophila egg. Our approach combines transport modeling and quantitative characterization of targeted gene expression systems in oogenesis. Using this method, we have estimated the magnitude of a dimensionless parameter that controls the Gurken gradient.We are currently extending this approach to analyze the terminal patterning system in the early embryo.Negative feedback in pattern formation systems:
Negative feedbacks are abundant in patterning networks, but both the biochemical basis of feedbacks and their functional significance are poorly understood at this time. Recent experiments in the Lemmon laboratory at UPenn have provided a detailed biochemical characterization of the biochemical action of Argos, an extracellular inhibitor that provides negative feedback for EGFR signaling in Drosophila. We are using this information to understand the mechanism of Argos action in the embryonic ventral ectoderm (VE). We are interested in determining both the spatial range of Argos and its contribution to the robustness in VE patterning.