Engineering researchers from Michigan State University in East Lansing are working to create synthetic biological devices inside the cells of mammals that will enable treatment for chronic and uncured diseases. The work is supported by a $1.3 million grant from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health.
A team of biomedical and electrical engineers will build biological circuits, oscillators, and toggle switches inside cells to respond to electromagnetic fields. The devices can tell a cell what to do to fight neurological illnesses and diseases. The work began earlier this summer.
“We’re trying to look at biology in a different way, more like engineers and less like traditional biologists,” says Assaf Gilad, professor of biomedical engineering and radiology at MSU and the grant’s primary investigator. “In synthetic biology, much like in electronics, we can use biological components to build a circuit that can perform a very specific function.”
A key factor is a navigational gene that has been cloned from the glass catfish, which responds to earth’s electromagnetic fields.
“We will bioengineer synthetic circuits from three bio-parts — a switch, an amplifier, and a reporter gene,” says Gilad. “MSU will be the first to build such circuits that function as a synthetic biological device in mammalian cells that will be remotely activated by a magnet and imaged noninvasively in rodents.”
Gilad says the biological circuit begins with a switch.
“Dr. (Galit) Pelled, (MSU professor of biomedical engineering, radiology, and neuroscience,) who is a neuroscientist, and I have been developing this switch in our laboratories for more than five years,” he says. “We discovered this genetically encoded switch, which changes the level of calcium inside the cells. We hypothesized that the glass catfish use such a gene for navigation, responding to magnetic fields, and therefore, we can use this gene as a switch that can be turned on and off with electromagnetic fields.”
He also says the gene can be an interphase between electronics and biological signals.
The second step is the amplifier.
“We have pilot data that shows that we have a second bio-part — an amplifier that can turn on and off different genes.”
Step three requires the ability for readouts or output, comparable to turning a light bulb on and off.
“With help from MSU professors (Erik) Shapiro (associate professor radiology,) and (Kurt) Zinn (professor of radiology and biomedical engineering), we will use MSU’s new combined positron emission tomography (PET) and magnetic resonance imaging (MRI) scanner to directly and non-invasively visualize those genes in mice. MSU is one of the first sites in the U.S. that will have a combined PET/MRI for small animal imaging.”
Other team members will begin to put the three bio-parts together, developing an electromagnet that will be used to remotely activate the switch and solving cell-to-cell communication.
“One of the most efficient ways to introduce such cells into the body is by constructing the circuits inside stem cells,” says Gilad. “Bioengineering of stem cells to function as biological devices inside the body has a great advantage. Similar to electronic circuits, you can replace the third bio-parts with other genes.”
For example, a scientist can place a therapeutic gene in a cell and put the circuits to work by suppressing or inducing genes that are aimed to kill cancer, can produce insulin for diabetes, or serve as neurotransmitters for neurological disease.
“The electromagnetic on/off switch in cells that MSU is working on will provide a huge advantage to the biomedical field,” says Gilad.
