Much faster directed evolution of proteins could speed development of molecular machine systems

One of the principal recommendations of the Technology Roadmap for Productive Nanosystems was to “Support the development of modular molecular composite nanosystems (MMCNs)” (see Productive Nanosystems: A Technology Roadmap, page 12 of 198-page PDF) in which large DNA frameworks (of the sort that we cited last week) are to be used to support relatively rigid functional objects of engineered proteins. Such proteins could be engineered through either rational design or directed evolution (for an excellent update on the latter see this post by Eric Drexler on Metamodern from October 2010). Laboratory-directed evolution can, however, be laborious, so anything to make it faster and easier might substantially advance this approach. Now ScienceDaily points to this Harvard Gazette article by Steve Bradt that announces a major improvement “Speeding up biomolecular evolution: New approach proves 100 times faster than before“:

Scientists at Harvard University have harnessed the prowess of fast-replicating bacterial viruses, also known as phages, to accelerate the evolution of biomolecules in the laboratory. The work, reported in the journal Nature [abstract], could ultimately allow the tailoring of custom pharmaceuticals and research tools from lab-grown proteins, nucleic acids, and other such compounds.

The researchers, led by Professor David R. Liu, say that their approach — dubbed “phage-assisted continuous evolution,” or PACE — is roughly 100 times faster than conventional laboratory evolution, and far less labor-intensive for scientists.

“Most modern drugs are based on small organic molecules, but biological macromolecules may be better suited as pharmaceuticals in some cases,” said Liu, a professor of chemistry and chemical biology at Harvard and an investigator with the Howard Hughes Medical Institute. “Our work provides a new solution to one of the key challenges in the use of macromolecules as research tools or human therapeutics: how to rapidly generate proteins or nucleic acids with desired properties.”

Liu and Harvard co-authors Kevin M. Esvelt and Jacob C. Carlson achieved up to 60 rounds of protein evolution every 24 hours by linking laboratory evolution to the life cycle of a virus that infects bacteria. This phage’s life cycle of just 10 minutes is among the fastest known. Because this generation time is so brief, the phage makes a perfect vehicle for accelerated protein evolution. The PACE system uses E. coli host cells to produce the resulting proteins, to serve as factories for phage production, and to perform the key selection step that allows phage-carrying genes encoding desired molecules to flourish.

In three protein evolution experiments, PACE was able to generate an enzyme with a new target activity within a week, achieving up to 200 rounds of protein evolution during that time. Conventional laboratory evolution methods, Liu said, would require years to complete this many rounds of evolution. …

It remains to be seen just how general this method will be since it depends on linking the activity to be evolved to protein production in bacteria. Nevertheless, it looks like the individual components of MMCN development are progressing nicely. Perhaps the next challenge is to see if the pieces can be put together to make effective molecular machine systems, leading eventually to atomically precise productive nanosystems.

New possibilities for solar energy with molecular 'stencils'

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This film of block copolymers shows the material's characteristic tendency to separate into distinct regions.

Scientists at the U.S. Department of Energy’s Argonne National Laboratory have begun to use molecular "stencils" to pave the way to new materials that could potentially find their way into future generations of solar cells, catalysts and photonic crystals.

Researchers at Argonne’s Center for Nanoscale Materials and Energy Systems Division have developed a technique known as sequential infiltration synthesis (SIS), which relies on the creation of self-assembled nanoscale chemical domains into which other materials can be grown. In this technique, a film composed of large molecules called block copolymers acts as a template for the creation of a highly-tunable patterned material.

This new method represents an extension of atomic layer deposition (ALD), a popular technique for materials synthesis that is routinely used by Argonne scientists. Instead of just layering two-dimensional films of different nanomaterials on top of one another, however, SIS allows scientists to construct materials that have much more complex geometries.

“This new technique allows us to create materials that just weren’t possible with ALD or block copolymers alone,” said Seth Darling, an Argonne nanoscientist who helped to develop SIS in collaboration with Argonne chemist Jeff Elam. “Having the ability to control the geometry of the material we’re making as well as its chemical composition opens the door to a whole universe of new materials.”

According to Darling, the success of the technique relies on the unique chemistry of block copolymers. Every block copolymer is composed of two chemically distinct subunits; for instance, one subunit might have an affinity for water while the other might repel water. In such a case, like would seek out like, creating a heterogeneous matrix of interspersed homogenous regions.

“You can think of a block copolymer as like a pair of molecular Siamese twins where one likes to talk and one likes to read quietly,” Darling said. “If you put a bunch of these twins together in a room, the talkative ones are going to try to be near the talkative ones and the readers are going to try to be near the readers, but they can’t simply all separate themselves to either side of the room, and it’s this action that gives us the geometries we’re looking for.”

Depending on the initial substrate, the block copolymers, and the processing that materials scientists use, regions can form that have many different shapes, from spherical to cylindrical to planar. While there are many types of block copolymers, in general they cannot serve as wide an array of purposes as inorganic materials. The challenge, according to Darling, is to bring the self-assembly of block copolymers together with the functionality of inorganic materials.

The physical and chemical properties of a material generated using SIS depend on how block copolymer chemistry and morphology interact with the chemistry of ALD techniques. “We can tailor our materials synthesis efforts in a much more precise way than we ever could before,” Darling said.

Darling and Elam have spent most of their careers at Argonne focused on the development of new types of materials, including the development of solar cells that combine organic and inorganic components. They believe that the types of materials that SIS can generate will drive fundamental solar energy technologies to greater efficiencies and lower cost.

“Our solar energy future does not have a one-size-fits-all solution,” Elam said. “We need to investigate the problem from many different angles with many different materials, and SIS will give researchers like us many new routes of attack.”

Provided by Argonne National Laboratory