|A new method for creating biological circuits from materials within a cell could significantly increase the number of genetic components in synthetic biologists’ toolkit and, as a result, the size and complexity of the genetic circuits they can build. The development could dramatically enhance their efforts not only to understand how biological organisms behave and develop, but also to reprogram them for a variety of practical applications.|
A new method developed by Assistant Professor Ahmad S. Khalil, Professor James J. Collins and collaborators at Harvard Medical School, Massachusetts General Hospital and MIT could significantly increase the number of genetic components in synthetic biologists’ toolkit and, as a result, the size and complexity of the genetic circuits they can build.
The development could dramatically enhance their efforts not only to understand how biological organisms behave and develop, but also to reprogram them for a variety of practical applications.
Described in the online edition of Cell, the technique offers a new method for constructing and analyzing genetic circuits in eukaryotes which includes organisms from yeasts to humans.
The research team built their synthetic genetic circuit parts from a class of proteins, known as zinc fingers, which can be programmed to bind desired DNA sequences. The modularity of the new parts enables a wide range of functions to be engineered, the construction of much larger and more complex genetic circuits than what’s now possible with bacteria-based parts, and ultimately, the development of much more powerful applications.
“Our research may lead to therapeutic applications, such as the dynamic modification and control of genes and genetic networks that are important in human disease,” said Khalil. Potential medical applications include stem cell therapeutics for a wide variety of injuries and diseases and in-cell devices and circuits for diagnosing early stages of cancer and other diseases. The new method may also equip groups of cells to perform higher-order computational tasks for processing signals in the environment in sensing applications.”
So far, the researchers built some simple circuits in yeast, but they plan to develop more complex circuits in future studies. “We didn’t build a massive 10- or 15-transcription factor circuit, but that’s something that we’re definitely planning to do down the road,” researcher Timothy Lu says. “We want to see how far we can scale the type of circuits we can build out of this framework.”
Synthetic biology circuits can be analog or digital, just like electrical circuits. Digital circuits include logic functions such as AND and OR gates, which allow cells to make unequivocal decisions such as whether to undergo programmed cell suicide. Analog functions are useful for sensors that take continuous measurements of a specific molecule in the cell or its environment. By combining those circuits, researchers can create more complex systems in which a digital decision is triggered once the sensor reaches a certain threshold.
In addition to building more complex circuits, the researchers are planning to try their new transcription factors in other species of yeast, and eventually in mammalian cells, including human cells. “What we’re really hoping at the end of the day is that yeast are a good launching pad for designing those circuits,” Lu says.
“Working on mammalian cells is slower and more tedious, so if we can build verified circuits and parts in yeast and them import them over, that would be the ideal situation. But we haven’t proven that we can do that yet.”