Cellular and Molecular Regulation of Embryonic Development
The molecular mechanisms of collective behavior among cells present a fundamental problem for biology. In pursuing this general question, my laboratory aims to understand the physical principles and mechanisms that lead seemingly homogenous populations of cells to differentiate. We take a unique approach to this problem by formulating fundamental biological questions that can only be addressed by precise quantitative measurements, providing an understanding that would not be obvious from mere qualitative observations. Our current research focuses on the initial steps of embryonic development in fruit flies and in mice, as well as the ability of starving amoebae populations to spontaneously aggregate. We develop new imaging tools -- microscopes, microfluidic devices, and molecular probes -- to quantify the spatiotemporal dynamics of inter-cellular signals.
Simple physical models can successfully describe collective behavior in many inanimate systems, such as phase transitions in condensed matter systems and pattern formation in chemical processes. Our understanding of analogous behavior in populations of cells, however, is only qualitative at best. For instance, much work has gone into characterizing the proteins and small molecules that pattern the early fruit-fly embryo, but few have addressed the basic physical problem of how these patterns form.
My laboratory takes a quantitative approach: we directly measure the spatiotemporal concentrations of important signaling molecules and correlate these measurements with the cells' responsive behavior. We then use this data to design and to test physical models of collective phenomena, some of which derive from similar behavior in inanimate systems, others of which are novel. To this end, we pursue research on both cellular and organismal systems: social amoebae, fruit fly embryos, and mouse embryos.
A larval fly develops from a finite set of components that are constricted to a fixed volume, the egg. This system is a paradigm of spontaneous biological self-assembly and an ideal organism for quantitative analysis. Furthermore, advanced genetics tools, a rapid generation time, and the ease of optical accessibility during early developmental stages afford an exquisite experimental control. In addition, we intend to extend our approach to mammals, working with mice embryos. We are in the initial phase of developing the microscopic tools to fluorescently image, in utero, the early embryonic stages during which the body axes are specified. To complement the approach with a more openly accessible system where external perturbations can be controlled with more accuracy, we are also interested in the early stages of the development of starved social amoebae populations.