Computing with Biochemical Circuits made Convenient

The Qian group has made the technology of DNA circuits accessible to even novoice scientists, comprising undergraduate students, using a software tool they introduced called the Seesaw Compiler. Now, they have experimentally illustrated that the tool can be used to quickly design DNA circuits that can then be built out of cheap, “non-purified” DNA strands, following a systematic wet-lab process devised by Qian and his team members.

Although, DNA is best known as the molecule that encodes the genetic data of living things, they are also useful chemical building blocks. This is because the smaller molecules that make up a strand of DNA, known as nucleotides, link together only with very specific rules, an A nucleotide links to a T, and a C nucleotide binds to a G. A strand of DNA is a sequence of nucleotides and can become a double strand if it binds with a sequence of complementary nucleotides.

DNA circuits are good at collecting data within a biochemical environment, processing the data locally and regulating the behaviour of individual molecules. Circuits built out of DNA strands instead of silicon transistors can be employed in absolutely distinct ways than electrical circuits. “A DNA circuit could add ‘smarts’ to chemicals, medicines, or substances by making their functions responsive to the changes in their environments,” says Qian. “More importantly, such adaptive functions can be programmed by humans.”

“The students in this study were undergrads and first-year graduate students majoring in computer science and bioengineering,” says Anupama Thubagere, a graduate student in bioengineering and biology and first author on the paper. “I instigated working with them as a head teaching assistant and together we soon identified that using the Seesaw Compiler to design a DNA circuit was convenient for everyone.”

However, building the designed circuit in the wet lab was not so easy. Thus, with the regular efforts after the class, the group set out to develop a systematic wet-lab process that could guide scientists, even novoices like undergraduate students, through the process of building DNA circuits. “Fortunately, we found a general solution to every limitation that we experienced, now making it convenient for everyone to build their own DNA circuits,” says Thubagere.

The group revealed that it was feasible to use cheap, ‘unpurified’ DNA strands in such circuits using the novel process. This was just possible as steps in the systematic wet-lab procedure were designed to compensate for the lower synthesis quality of the DNA strands.