Dynamics of cellular proliferation and maturation; dynamics of gene regulation

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This research is a combined exploration of gene regulation in prokaryotes and eukaryotes and the regulation of hematopoietic cellular proliferation and maturation at the whole organ level. The long term goal of the research on gene regulation is to add to the catalog of systems in which we can understand their dynamic regulation as well to understand the role of noise at the single cell level in determining population level responses. The work on gene regulation is extremely fundamental in the sense that I am exploring how both intrinsic and extrinsic noise can shape and alter dynamics at the gene expression level, and is adding to the catalog of knowledge we have for these systems that lie at the heart of all biological processes. The goal for this grant application period is to simultaneously explore the genetic and metabolic aspects of galactose regulation (something that has not been done before in a mathematical modeling context), and to understand the interplay between temporal and spatial aspects of gene regulation in generating pattern formation in the sea urchin embryo. The long term goal of my work on hematopoiesis is to develop a complete mathematical model for how a normal organ maintains itself through cellular proliferation and maturation. I have been able to use observations of dynamically oscillating blood cell populations to great advantage in untangling a variety of cellular regulatory mechanisms responsible for homeostasis. For the duration of this grant period my more immediate goal is to produce an accurate model for the regulation of megakaryocyte nuclear replication and the subsequent formation of platelets. This process is physiologically interesting (since in involves nuclear replication without mitosis) and involves significant new mathematics because of the state dependent delays involved that are mediated by thrombopoietin.