Background. One of the greatest contrasts between the biological organisms and human technology lies in how they are constructed. Plants and animals grow from the inside out, often from a single cell to an organism containing billions of cells, each of which is built from molecular components that are manufactured with atomic precision within the cell. In contrast, mankind's greatest engineering marvels, such as airplanes and skyscrapers and computers, are put together from the outside in, with components being manufactured in factories and assembled piece by piece. This distinction is often referred to as "bottom-up" vs "top-down" assembly in the biological "bottom-up" approach, the assembly process is guided by the components themselves, while in the engineering "top-down" approach, there is an entity conceptually above the object being built that supervises and guides the manufacturing process. Human engineering has mastered top-down methods to create systems of great complexity (but has not extended them to the atomic and molecular scale) and has exploited bottom-up methods for the synthesis of diverse molecular, polymeric and crystalline structures (but has not created information-rich structures of great complexity). Project Goals. Our goal is to demonstrate how bottom-up techniques can create complex atomically-defined structures, as biology does, by embedding information and computational processes within the molecules themselves. In biological development, a program (the genome) uses biochemistry to guide the growth process and determine the ultimate form of the organism. In the parlance of computer science, a system that can be programmed to accomplish any task that can be accomplished is called a "universal" system. A universal computer can be programmed to perform any computation, while a universal constructor can be programmed to carry out any construction task. Recent work has theoretically shown that universal molecular self-assembly is possible and has experimentally demonstrated that the approach shows promise, using DNA as a construction material to create functional molecular devices so-called "DNA nanotechnology". In this proposal, we aim to bring DNA nanotechnology to the point where universal bottom-up self-assembly can be achieved well enough that immediate technological applications can be demonstrated. Specific Aims. We aim to make major advances both in our ability to program complex self-assembly logic and in our ability to interface the DNA structures to chemically-, optically-, and electronically-relevant materials. We will focus on four main goals, which span the range from long-term fundamental work to near-term development: (1) self-assembly of a template for a complex molecular-scale electronic circuit; (2) programming the behavior of molecular walking motors to transport components in nanofabrication tasks; (3) attaching carbon nanotube wires to create small nanoscale electronic circuits; and (4) integrating bottom-up and top-down fabrication by placing and orienting self-assembled components at target locations on silicon wafers with functional electrical contacts. Uniquely, the aims of this research require simultaneously development of two novel computing systems: the first, inspired by biological self-assembly and development, operates at the level of molecular machines and biochemistry, and will be programmed to construct the second, composed of carbon nanotubes assembled into nanoscale circuits, which operates at the electrical level like conventional computing devices. Broader Impact. An important aspect of this project will be the training of young scientists (undergraduates, graduate students, and postdocs) capable of spanning the interdisciplinary subjects involved in this work.