With funding from the highly competitive Human Frontier Science Program, an international team including The University of Texas at Austin's Andrew Ellington plans to unravel billions of years of evolution to create an ancient version of a cell.
Using synthetic biology, the interdisciplinary team will create a cell that uses RNA enzymes, called ribozymes, to recapitulate a key step in the evolution of life on Earth: the establishment of the genetic code and the invention of translation—a process that builds useful molecules based on the genetic code.
In modern cells, there are three major types of molecules that perform the functions of life: DNA, RNA and proteins. Proteins are the workhorses, doing things like speeding up chemical reactions, forming structures, breaking down molecules, transporting substances and attacking foreign pathogens. DNA stores the genetic code, or blueprints for building the proteins, and RNA builds the proteins. But some scientists have argued that more ancient cells might have only used RNA and ribozymes to carry out many of the same functions; DNA came along later in evolution. This is called the RNA World hypothesis.
"Our project brings together the best of chemistry, biochemistry, biochemical engineering and molecular evolution to address a problem that has been untouchable in the past," said Ellington, professor of molecular biosciences and the project's principal investigator.
"It has long been hypothesized that modern cells evolved from an 'RNA world'," said Michael Jewett, associate professor of chemical and biological engineering and co-director of Northwestern University's Center for Synthetic Biology. "We wonder if this hypothesis is true, and seek to ask the question if it is possible to move back our current, protein-based biological world to look more like an ancient RNA-based one," said Jewett.
The Human Frontier Science Program challenges life scientists to identify important problems in their disciplines and then tackle them in new ways. Selected projects receive three years of support. Team members must represent at least two different countries.
In addition to Ellington and Jewett, the team also includes Philippe Marliere, synthetic biologist at Genopole Evry in France and Hiroaki Suga, professor of chemistry at the University of Tokyo.
Information encoded in DNA and RNA enables the synthesis of proteins to perform a wide array of functions in modern living cells, including metabolic function and DNA replication. The team plans to build a replicating organism that may lead to the development of a more ribozyme-centric information flow. Not only could this illuminate why cells needed to evolve to make proteins, the project could also help scientists understand how to use evolutionary optimization to build complex systems such as the one underlying the process of translation.