The Biophysics of Organismal Development

In spite of the progress in molecular biology over the last 3 decades,1 we are still searching for the mechanisms that generate complex spatial patterns of cellular differentiation and morphology. While the core patterning genes - those responsible for laying out the blueprint of the body plan - are small in number and strikingly conserved, the number of molecules involved in reading and executing the blueprint is vast. Central to “reading of the blueprint” are thousands of proteins and regulatory genes participating in the patterning of physical forces that give rise to complex spatial patterns of gene expression and morphology. The physical and chemical form of multicellular organisms is therefore a complex trait. Addressing complex traits requires a phenomenological treatment, juxtaposing the kinds of analyses that help us understand why some people have blue eyes - a decidedly Mendelian and simple trait. From this point of view, the approach I propose bears a striking resemblance to Condensed Matter Physics, which studies the emergent macroscopic properties of materials that are a collection of a vast number of molecular components. With this in my mind, my work is focused on constructing measurement tools and models for organismal development from a necessarily phenomenological perspective. In particular, models form the bases of inference schemes that permit the quantitative measurement of biophysical parameters directly from live-imaging data, which we do not have direct experimental access to. Combining these biophysical measurements with fluorescent proxies for genetic and protein activity permits the construction of mathematical models for organismal dynamics at the scales they are manifest. New models form the bases of future hypotheses, experimental predictions, and inference schemes. Central to my work is the development of image analysis tools, and collaborations with experimental labs around the world with an expertise in live-imag