Sometimes big advances in science happen without much public notice. That’s often because at the time they didn’t look like big advances in science, or just as likely, they were considered marginally workable, so nobody wanted to highlight them. Here’s one such case to consider: Researchers at Yale University (Connecticut, USA) and publishing in the journal Science [26 August 2011, paywalled, Expanding the Genetic Code of Escherichia coli with Phosphoserine] have announced the use of synthetic biology techniques to add new DNA to an old friend of the lab, Escherichia coli (E. coli). The new DNA does something never done before: It produces new forms of proteins with the ability to phosphorylate.
I can see the “?” form over your head. I’ll explain in a bare moment, but first the “Why?” Using the new DNA, biochemists will be able to create proteins that mimic disease conditions, or components of diseases – and turn them on or off as part of experimental testing. Doing this should give scientists much greater insight into the role of proteins in diseases and how to control them. In short, it creates a kind of ‘sandbox’ (controlled) environment to test hypotheses about diseases and how they work. Now, for a bit of explanation…
The place to start is with the concept of phosphorylation. This is what happens to proteins when a phosphate group (PO4) is added, it activates (or deactivates) the protein (often an enzyme) like a chemical on-off switch. Phosphorylation is one of the most fundamental of biochemical processes, used within cells for an untold number of chemical pathways, and the subject of an enormous amount of research. Interestingly, although phosphorylation is crucial to the timing and control of many biological processes, it is not something directly controlled by DNA. It falls into the area known as epigenetics, genetic (reproducible and sometimes inheritable) characteristics that occur largely outside of the usual DNA/RNA mechanics.
What the Yale researchers did is take the phosphorylation capability and code it into the genome, into the DNA of E. coli, a remarkable technical feat. They added the ability to synthesize phosphoserine, a key compound in the phosphorylation of enzymes (among other things), and added it to the natural bag of genetic tricks – using synthetic biology to produce a new form of natural biology (so to speak).
The outcome of adding new DNA to E. coli is that the bacteria can produce ‘natural’ proteins, proteins that scientists choose to create, that have the phosphorylation capability built into them.
“Essentially, we have expanded the genetic code of E. coli, which allows us synthesize special forms of proteins that can mimic natural or disease states,” said Jesse Rinehart co-corresponding author of the research. “What we have done is taken synthetic biology and turned it around to give us real biology that has been synthesized.”
This does sound like a new sandbox to play in, but there are probably rules and limitations built into this sandbox that are yet to be discovered. I’m using the sandbox analogy to emphasize that while the ability to synthesize phosphorylate proteins via DNA is a powerful concept, it may yet prove to have problems in practice. It’s certainly possible that synthesizing disease proteins with phosphorylation built-in is a key to understanding the interaction of living proteins and disease conditions. However, there is more – much more – to the complexity of biological processes that is not well understood, especially in the area of epigenetics. A few years down the road, and the techniques used in this research may be deemed ‘flawed’ or ‘too difficult’ or any number of other conditions that will sideline the technique. Or this could be the beginning of a highly successful approach that opens the research doors to the understanding of many forms of disease. Hopefully so.
The next steps for the Yale team is to actually manufacture proteins for diseases such as cancer(s), type 2 diabetes and hypertension (for example) and put them into experimental environments where they can be observed in vivo or in vitro.