New gene-editing system enables large-scale studies of gene function.
CAMBRIDGE, Mass. -- It's not exactly "ET, phone home," but researchers at the Massachusetts Institute of Technology report in the January 10 issue of Nature that they can "speak" to DNA biomolecules with radio waves.
The goal is to instruct biological materials how to act for a variety of purposes. Biological machines may one day be used to perform computation, assemble computer components or become part of computer hardware or circuitry. Radio-controlled biology may lead to single-atom or single-molecule machines or the ability to hook tiny antennae into living systems to turn genes on and off.
"Recent studies have provided new insights into the complexity, precision and efficiency of biomolecular machines at the molecular scale, inspiring the development of physical and chemical manipulation of biological systems," said Joseph M. Jacobson, associate professor at the MIT Media Lab and an author of the study. "Manipulation of DNA is interesting because it has been shown recently that is has potential as an actuator (a hard drive component) and can be used to perform computational operations."
MIT researchers predict that radio frequency (RF) biology will have a broad range of applications. Because virtually all biological molecules can be linked with gold or other semi-conducting nanoparticles, these molecules can be controlled electronically, remotely, reversibly and precisely, says Shuguang Zhang , associate director of MIT's Center for Biomedical Engineering and one of the study's authors. Such systems will have profound implications for finely dissecting detailed molecular interactions and formations, he said.
Jacobson, head of the Media Lab's Molecular Machine group , has a background in quantum physics. He became interested in using biology as a tool to create nanometer-length machines. The ultimate goal, he said, is a machine on the single-atom or single-molecule level.
It's hard to manufacture computer chips much smaller than 30 nanometers, but biology has an excellent track record at creating tiny workable systems. The cell itself is a phenomenal little machine with its own power supply and memory. "If we're interested in molecular-scale machines, biology is a wonderful place to start," Jacobson said.
He worked with researchers from MIT's Center for Biomedical Engineering to attach tiny radio-frequency antennae -- a metal nanocluster of less than 100 atoms -- to DNA.
When a radio-frequency magnetic field is transmitted into the little antennae, the molecule is zapped with energy and responds.
Hybridization is the process of joining two complementary strands of DNA or one each of DNA and RNA to form a double-stranded molecule. In dehybridization, the strands unwind. Using this technique, the researchers dehybridized double-stranded DNA in a matter of seconds. The switching is reversible, and did not effect neighboring molecules.
Nanocrystals can be attached to proteins as well as to nucleic acids. This opens the possibility of switching more complex processes such as enzymatic activity, biomolecular assembly, gene expression and protein folding. The function of cells' components and the cell life cycle itself may be electronically regulated with radio frequency, Jacobson said.
The goal is build molecules into systems that turn on and off depending on the electronic commands they receive. It may one day be possible to hook the antennae into living systems and turn genes on and off. "There are already numerous examples of nanocrystals attached to biological systems for the purpose of sensing," said co-author Kimberly Hamad-Schifferli , a postdoctoral associate in the MIT Media Lab. "However, we hadn't come across any examples where they are used as a means of controlling the biology."
SEEKING ULTIMATE ANSWERS
"The development of molecular biology has witnessed many examples of ways to design new tools that accelerated uncovering nature's secrets," Zhang said. "Regulation of biomolecules using electronic RF control represents a new dimension in biology."
The exquisitely fine electronic controls of biological regulation will likely become more and more important in understanding complex molecular interactions in great detail, he said, because there is currently no other way to achieve fine local control without disturbing neighboring molecules. He likened the level of communication to using a mobile phone to convey a message to a single person in a crowd.
"Radio frequency biology provides us with some extraordinary tools and with unprecedented precision controls to study biomolecules and their interactions. These new tools and technologies will undoubtedly accelerate and advance our knowledge in finest detail. It not only opens new avenues for us to ask big and deep questions but also to attain the ultimate answers in biology," Zhang said.
In addition to Jacobson, Hamad and Zhang, the study's authors are John J. Schwartz, a former postdoctoral associate in MIT's Center for Biomedical Engineering who now works for a company called engeneOS in Waltham, Mass., and MIT student Aaron Santos. Jacobson and Zhang also are affiliated with engeneOS, which designs and builds programmable biomolecular devices consisting of natural and non-natural materials for commercial applications.
This work is funded by the Defense Advanced Research Projects Agency (DARPA) and the Things That Think consortium at the MIT Media Lab.