CAREER: Expanding the Scope of Nucleic and Protein Evolution

Harvard University, Cambridge MA

Investigators

Abstract

0094128 David Liu The ability of chemists and biologists to manipulate molecules of increasing complexity has exerted a profound influence on our understanding of the processes driving life. Nature employs a powerful version of generating variants of molecules and correlating their new structures and functions in the form of molecular evolution. The dominance of proteins and nucleic acids among solutions to complex chemical problems, despite the limited chemical functionality of these molecules, is a dramatic testament to the power of iterated cycles of diversification, selection, and amplification. Researchers have recently harnessed this power to artificially evolve proteins and nucleic acids with new properties. This CAREER project seeks to expand the scope of molecular evolution by addressing two current limitations. First, because each cycle of molecular evolution relies on the diversification of molecular structure, the development of general methods to more intelligently sample the vast sequence space of a biopolymer would represent a major advance in the ability to evolve all types of biopolymers. Second, the development of methods to apply molecular evolution to more types of biologically important macromolecules such as protein-RNA complexes may lead to advances both in the basic understanding of these molecules and in the ability to generate new molecules with tailor made properties. Molecular evolution is representative of chemical biology, a term used to describe the manipulation of structures and functions of molecules to study biological phenomena. Although chemical biology is having an enormous impact on many areas of science, the rapidly changing and multidisciplinary nature of chemical biology together with the effort required to depart from standard textbooks in biological chemistry have resulted in its under-representation in curricula at both the undergraduate and graduate levels. Early and in-depth exposure to chemical biology is now a prerequisite for any complete modern education in chemistry or biology. As part of the education component of this CAREER project, a course for graduate students and advanced undergraduates has been constructed from more than 800 recent papers covering many of the most important and cutting-edge topics in chemical biology, including genomics, proteomics, combinatorial chemistry, chemical genetics, protein design and engineering, and molecular evolution.