We study life-like biochemical systems to understand their fundamental properties and address emerging challenges in biotechnology and infectious disease. Our focus is biomolecular design and evolution in two nanoscale systems: simple synthetic cells and bacteriophages (phages).

In the space of all possible sequences, fitness, or biochemical activity, defines a landscape. Evolution is the process of exploring this landscape and climbing the peaks. Combining in vitro evolution with massive sequencing creates the first maps of molecular fitness landscapes. We study the evolution of catalytic RNA, which could be the basis of primitive life, to understand fundamental questions about chance and natural selection. Encapsulation of functional RNA into simple cells can lead to unexpectedly rich behaviors.

In addition to being the most numerous biological entity on earth, phages have evolved mechanisms to subvert bacterial biology and destroy bacterial cells. Yet most phages are essentially uncharacterized. We study the potential natural role of phages in bacterial infections. Furthermore, phages possess certain advantages for therapeutic and diagnostic goals, but their safety and predictability are problematic. We explore strategies to control and harness phages for desired applications.