The biological machines we plan to build are composed of specialized cellular and molecular components that dynamically interact to coordinate the larger system functions of biological  machines. Initially it is important to understand the characteristics of the plethora of cells and their components and how they behave upon differentiation leading to a coordinated functional machine and what roles they play in replacing worn parts within an active biological machine. We will determine in real time, using enabling technologies (reporter genes, matrices etc.), how stem cells and progenitor cells exposed to intrinsic and extrinsic cues behave and interact in a coordinated fashion.  This new understanding will aid in the creation of the emerging cell clusters that form the individual systems and that are ultimately integrated to produce biological machines. Therefore it is important to understand how to make available differentiating cells that meet the machine’s specifications, and how to predict and control phenotypic changes. A unique aspect of this project is the use of emerging technologies and computational tools to understand in real time and eventually predict the complex nature of cell function(s) of differentiating cells in a defined and controlled microenvironment.