Frances Arnold

Frances Arnold won the 2018 Nobel Prize in Chemistry!!!! It was awarded for her work on directed evolution, and if you want to know more about it (and her) you're in luck because she's today's #WiSEWednesday honoree! (A Nobel & a #WiSEWednesday in the same day!)

Arnold researches directed evolution to design enzymes (molecules that speed up chemical reactions) that perform novel functions and/or work more effectively or efficiently than natural enzymes. In nature, evolution by natural selection can lead to proteins (including enzymes) well-suited to carry out biological tasks, but natural selection can only act on existing sequence variations (mutations) and typically occurs over long time periods. Arnold speeds up the process by introducing mutations in the sequences of proteins; she then tests these mutations' effects. If a mutation improves the proteins' function she can keep iterating the process to optimize it further.

This strategy has broad implications because it can be used to design proteins for a wide variety of applications. For example, she has used directed evolution to design enzymes that can be used to produce renewable fuels and pharmaceutical compounds with less harm to the environment.

The number of possible mutation combinations is astronomical - instead of just randomly trying to test as many as possible, Arnold integrates her knowledge of biochemistry to narrow down the options, focusing on introducing mutations in areas of the protein that are likely to have the most positive effect on activity and avoiding areas in which mutations would likely be, at best, neutral and at worst, detrimental (such as disrupting proper protein folding).

Arnold also uses structure-guided protein recombination to combine parts of different proteins to form protein chimeras with unique functions. She uses computational methods to predict how the parts can be combined without disrupting their parental structure, so that the chimeras will fold properly, and then applies directed evolution to further mutate the chimeras to optimize their functions.

Arnold studied mechanical and aerospace engineering at Princeton, then earned a PhD in chemical engineering from the University of California, Berkeley (UC Berkeley) in 1985. She joined the California Institute of Technology (CalTech) in 1986, where she is now the Linus Pauling Professor of Chemical Engineering, Bioengineering, and Biochemistry.

Photo: CalTech

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