Humans and nature use radically different principles to solve design problems. When building machines, human engineers tend to think in terms of discrete subunits, each with a unique function, coming together to create something greater—the motherboard, processor, graphics card, hard drive, and RAM combine to create a computer, for instance. Nature, however, works with a different set of design principles. While different parts of an organism certainly have unique functions, those functions are often not realized in discrete subunits but are instead distributed throughout the organism. If we look at systems only through our own approach to design, we might fail to understand biological systems and limit our ability to create in interesting ways.  This grant supports Donald Ingber at Harvard University who, together with a talented team of biologists, is exploring one of nature’s ubiquitous designs: hierarchical self-assembly. In Earth biological life, hierarchical self-assembly is achieved through nucleic acid subunits coming together to form intricate strands of DNA which, in turn, go on to guide cell development and differentiation. Grant funds allow the team to explore how aspects of molecular structure contribute to these critical, wide-ranging functions. First, they will use simulations to design different DNA-based molecular scaffoldings. Next, they will build physical copies of these scaffoldings and take measurements to see how the properties compare in reality. Finally, they will grow cells on the different scaffolding combinations to understand how the underlying structure impacts distributed functions throughout the cell. Ultimately, the set of experiments aims to advance our understanding of self-organization across multiple scales—and how variations in underlying DNA structures can impact functions at the cell, tissue, and organism level.