My friends in the Silver Lab are constantly doing amazing things, and I want to highlight two papers from last summer that are especially amazing. Both papers rethink the role of nucleic acids (DNA and RNA) in synthetic biology in really interesting and unexpected ways.
DNA is often called the "code" or "blueprint" of life, the sequence of letters that defines the proteins that make up a cell. In synthetic biology, new pathways are built by assembling different pieces of DNA and putting them into a cell. Karmella Haynes, now setting up her own lab at Arizona State University, set out to not just create new sequences of DNA, but to alter how DNA is read by the cell. In human cells, DNA is wrapped around protein nubbins called histones, which wind the DNA tight enough to pack 1.8 meters of DNA into about 120 micrometers (.00012 meters) worth of chromosomes. The histones don't just wind up the DNA, they also control which stretches of DNA are actively being read and turned into proteins. Adding carbon atoms onto one spot on the histones tells the cell not to read the sequence of DNA wrapped around that histone, silencing the gene. By mixing a protein that recognize these silencing histones and combining it with proteins that activate expression of genes, Karmella was able to turn on genes that were previously silenced in the cell. In cancer cells, genes that tell the cell to stop growing are often silenced, and Karmella saw that these genes turned on when she added her synthetic protein, making the cancer cells stop growing.
The cover art for the journal is also by Karmella, who's not just a phenomenal scientist but also an amazing artist (she even painted her poster at a recent conference!). Check out the paper: Karmella A. Haynes and Pamela A. Silver. (2011), Synthetic Reversal of Epigenetic Silencing, Journal of Biological Chemistry, 286 (31): 27176.
DNA is a code that can be turned on or off, but it's also a really interesting physical molecule, a sturdy double helix that can be programmed to bend into different shapes not found inside cells, the focus of a new field called DNA nanotechnology. Because A always pairs with T and G pairs with C, different sequences can be made that pair in shapes besides the standard double helix. RNA, on the other hand, is an information molecule that wears many hats inside of the cell. It's the go-between between DNA and protein, but it can also fold itself up into complicated shapes with many different functions inside the cell. Camille Delebecque with Faisal Aldaye, an expert in DNA nanotechnology, wondered if RNA could also be used as a programmable material to build a sturdy scaffold inside the cell. They designed short stretches of RNA that would bind to each other in such a way that they made long sheets or tubes, with docking sites for proteins to bind along the RNA scaffold. These docking sites could bring proteins closer together inside of a cell, making certain biochemical reactions happen faster, something that can be useful in many synthetic biology applications.
Check out the paper in the July 22nd issue of Science: Camille J. Delebecque, Ariel B. Lindner, Pamela A. Silver, and Faisal A. Aldaye. (2011) Organization of Intracellular Reactions with Rationally Designed RNA Assemblies. Science, 333 (6041): 470.
Both of these papers are just the beginning of exciting research into new approaches to synthetic biology, and I'm looking forward to hearing more from these great scientists and these interesting new avenues of research.