Science Discussion: We are researchers at Caltech working with Professor
Frances Arnold, one of the recipients of the 2018 Nobel Prize in
Chemistry. We use directed evolution to engineer proteins to do
chemistry not found in nature (yet). Let’s Discuss!!
Abstract
Hi Reddit, We are graduate students and postdocs in Professor Frances
Arnold’s research group at Caltech. We use directed evolution, the
algorithm for which Frances won the Nobel Prize last week, as a tool to
engineer proteins. Directed evolution, like Darwinian evolution, is
about “survival of the fittest” by selecting beneficial mutations that
enhance a desired function. The key difference is that in directed
evolution the person running the experiment chooses which mutations are
beneficial – in other words, we choose the definition of “fittest” in
“survival of the fittest.” Understanding how a protein’s sequence
connects to its structure is challenging (relevant XKCD), and
understanding how that structure confers function is another significant
challenge. A strength of directed evolution is that one does not need to
know a lot about the protein to use it; all one needs is the genetic
information (the DNA that encodes the protein of interest) and a way of
testing each variant for the function of interest. We don’t need to know
exactly how or why the protein is able to catalyze a reaction or
understand why a mutation enhances that activity. Proteins have been
engineered using directed evolution for myriad uses, from higher
stability for use in your laundry detergent to remove stains to
producing blockbuster pharmaceutical compounds in place of less
environmentally friendly syntheses. Unfortunately Frances is not able to
join us for the discussion, but we are happy to answer any questions you
have about directed evolution, proteins, Caltech, and beyond! Useful
links on directed evolution: “What is directed evolution and why did it
win the chemistry Nobel prize?” from Chemistry World C&EN Online
explanation of directed evolution and phage display Frances discussing
the Nobel Prize on NPR’s Science Friday TEDxUSC talk by Frances: “Sex,
Evolution, and Innovation” Learn more about the Arnold Group:
http://fhalab.caltech.edu/ Follow Dr. Arnold on Twitter:
https://twitter.com/francesarnold Our discussion panel guests today are:
Anders Knight ( /u/AndersKnight ): Anders is a fourth-year
bioengineering graduate student in the Arnold lab. He works on
engineering heme proteins to do carbene transfer reactions not found in
nature. An open-access paper on these kinds of reactions is available
here. Kari Hernandez ( /u/Kari_Hernandez ): Kari is in the 4th year of
her Ph.D. and received her B.S. in chemical engineering from the
University of Arizona. Her work focuses on making useful molecules by
evolving heme proteins to do non-natural reactions. Jennifer Kan (
/u/JennyKan ): Jenny is a postdoc in Frances Arnold’s lab at Caltech.
Her favourite thing to do is to teach proteins to make cool bonds.
Twitter: @sbjennykan Tina Boville ( /u/TinaBoville ): Tina is a postdoc
in the Arnold lab evolving enzymes to make chemical building blocks
called noncanonical amino acids. She is very interested in green
chemistry and lab sustainability and is a fellow at the Resnick
Institute. Patrick Almhjell ( /u/PatrickAlmhjell ): Patrick is a
second-year graduate student in the Biochemistry and Molecular
Biophysics program at Caltech, working on the same project as
/u/TinaBoville. Patrick loves chemistry but not the chemistry lab, so he
appreciates being able to use enzymes in water instead. An open-access
review on noncanonical amino acid synthesis is available here. Kevin
Yang ( /u/KevinKYang ): Kevin is a 5th year PhD student in Frances
Arnold’s lab. His research focuses on using machine learning to
accelerate directed evolution. Read his open-access paper on using
machine learning in protein engineering. Zach Wu ( /u/zvxywu ): Zach is
a 4th year graduate student in Chemical Engineering. His research
focuses on developing methods for engineering proteins efficiently and
understanding the sequence function relationship. Our guests will begin
answering questions starting at 1:00PM PST.