Computing with biochemical circuits made easyFebruary 23, 2017
Electronic circuits are found in almost everything from smartphones to spacecraft and are useful in a variety of computational problems from simple addition to determining the trajectories of interplanetary satellites. At Caltech, a group of researchers led by Assistant Professor of Bioengineering Lulu Qian is working to create circuits using not the usual silicon transistors but strands of DNA.
The Qian group has made the technology of DNA circuits accessible to even novice researchers--including undergraduate students--using a software tool they developed called the Seesaw Compiler. Now, they have experimentally demonstrated that the tool can be used to quickly design DNA circuits that can then be built out of cheap "unpurified" DNA strands, following a systematic wet-lab procedure devised by Qian and colleagues.
A paper describing the work appears in the February 23 issue of Nature Communications.
Although DNA is best known as the molecule that encodes the genetic information of living things, they are also useful chemical building blocks. This is because the smaller molecules that make up a strand of DNA, called nucleotides, bind together only with very specific rules--an A nucleotide binds 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 information within a biochemical environment, processing the information locally and controlling the behavior of individual molecules. Circuits built out of DNA strands instead of silicon transistors can be used in completely different ways than electronic circuits. "A DNA circuit could add 'smarts' to chemicals, medicines, or materials by making their functions responsive to the changes in their environments," Qian says. "Importantly, these adaptive functions can be programmed by humans."
To build a DNA circuit that can, for example, compute the square root of a number between 0 and 16, researchers first have to carefully design a mixture of single and partially double-stranded DNA that can chemically recognize a set of DNA strands whose concentrations represent the value of the original number. Mixing these together triggers a cascade of zipping and unzipping reactions, each reaction releasing a specific DNA strand upon binding. Once the reactions are complete, the identities of the resulting DNA strands reveal the answer to the problem.
With the Seesaw Compiler, a researcher could tell a computer the desired function to be calculated and the computer would design the DNA sequences and mixtures needed. However, it was not clear how well these automatically designed DNA sequences and mixtures would work for building DNA circuits with new functions; for example, computing the rules that govern how a cell evolves by sensing neighboring cells, defined in a classic computational model called "cellular automata.
"Constructing a circuit made of DNA has thus far been difficult for those who are not in this research area, because every circuit with a new function requires DNA strands with new sequences and there are no off-the-shelf DNA circuit components that can be purchased," says Chris Thachuk, senior postdoctoral scholar in computing and mathematical sciences and second author on the paper. "Our circuit-design software is a step toward enabling researchers to just type in what they want to do or compute and having the software figure out all the DNA strands needed to perform the computation, together with simulations to predict the DNA circuit's behavior in a test tube. Even though these DNA strands are still not off-the-shelf products, we have now shown that they do work well for new circuits with user-designed functions."
"In the 1950s, only a few research labs that understood the physics of transistors could build early versions of electronic circuits and control their functions," says Qian. "But today many software tools are available that use simple and human-friendly languages to design complex electronic circuits embedded in smart machines. Our software is kind of like that: it translates simple and human-friendly descriptions of computation to the design of complex DNA circuits."
The Seesaw Compiler was put to the test in 2015 in a unique course at Caltech, taught by Qian and called "Design and Construction of Programmable Molecular Systems" (BE/CS 196 ab). "How do you evaluate the accessibility of a new technology? You give the technology to someone who is intellectually capable but has minimal prior background," Qian says.
"The students in this class were undergrads and first-year graduate students majoring in computer science and bioengineering," says Anupama Thubagere, a graduate student in biology and bioengineering and first author on the paper. "I started working with them as a head teaching assistant and together we soon discovered that using the Seesaw Compiler to design a DNA circuit was easy for everyone."
However, building the designed circuit in the wet lab was not so simple. Thus, with continued efforts after the class, the group set out to develop a systematic wet-lab procedure that could guide researchers--even novices like undergraduate students--through the process of building DNA circuits. "Fortunately, we found a general solution to every challenge that we encountered, now making it easy for everyone to build their own DNA circuits," Thubagere says.
The group showed that it was possible to use cheap, "unpurified" DNA strands in these circuits using the new process. This was only possible because steps in the systematic wet-lab procedure were designed to compensate for the lower synthesis quality of the DNA strands.
"We hope that this work will convince more computer scientists and researchers from other fields to join our community in developing increasingly powerful molecular machines and to explore a much wider range of applications that will eventually lead to the transformation of technology that has been promised by the invention of molecular computers," Qian says.
California Institute of Technology
Related Dna Articles:
New license-free tools will allow researchers to estimate the size of DNA fragments for a fraction of the cost of currently available methods.
How can long DNA filaments, which have convoluted and highly knotted structure, manage to pass through the tiny pores of biological systems?
Since a couple of decades, metal-containing drugs have been successfully used to fight against certain types of cancer.
A Caltech-led study has shown that the electrical wire-like behavior of DNA is involved in the molecule's replication.
DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices.
Northwestern University biomedical engineers have developed imaging technology that is the first to see DNA 'blink,' or fluoresce.
A Salk team developed a tool that maps functional areas of the genome to better understand disease.
In a carefully designed polymer, researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences have imprinted a sequence of a single strand of DNA.
The African clawed frog X. laevis genome contains two full sets of chromosomes from two extinct ancestors.
Church's team at Harvard's Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School developed a new electronic DNA sequencing platform based on biologically engineered nanopores that could help overcome present limitations.
Related Dna Reading:
DNA: The Story of the Genetic Revolution
by James D. Watson (Author), Andrew Berry (Author), Kevin Davies (Author)
The definitive insider's history of the genetic revolution--significantly updated to reflect the discoveries of the last decade.
James D. Watson, the Nobel laureate whose pioneering work helped unlock the mystery of DNA's structure, charts the greatest scientific journey of our time, from the discovery of the double helix to today's controversies to what the future may hold. Updated to include new findings in gene editing, epigenetics, agricultural chemistry, as well as two entirely new chapters on personal genomics and cancer research. This is the most comprehensive and... View Details
The Family Tree Guide to DNA Testing and Genetic Genealogy
by Blaine T. Bettinger (Author)
Unlock the secrets in your DNA!
Discover the answers to your family history mysteries using the most-cutting edge tool available. This plain-English guide is a one-stop resource for how to use DNA testing for genealogy. Inside, you'll find guidance on what DNA tests are available, plus the methodologies and pros and cons of the three major testing companies and advice on choosing the right test to answer your specific genealogy questions. And once you've taken a DNA test, this guide will demystify the often-overwhelming subject and explain how to interpret DNA test results,... View Details
The Four: The Hidden DNA of Amazon, Apple, Facebook, and Google
by Scott Galloway (Author)
NEW YORK TIMES BESTSELLER
USA TODAY BESTSELLER
Amazon, Apple, Facebook, and Google are the four most influential companies on the planet. Just about everyone thinks they know how they got there. Just about everyone is wrong.
For all that’s been written about the Four over the last two decades, no one has captured their power and staggering success as insightfully as Scott Galloway.
Instead of buying the myths these companies broadcast, Galloway asks fundamental questions. How did the Four infiltrate our lives so completely that... View Details
DNA: A Graphic Guide to the Molecule that Shook the World
by Israel Rosenfield (Author), Edward Ziff (Author), Borin Van Loon (Author)
With humor, depth, and philosophical and historical insight, DNA reaches out to a wide range of readers with its graphic portrayal of a complicated science. Suitable for use in and out of the classroom, this volume covers DNA's many marvels, from its original discovery in 1869 to early-twentieth-century debates on the mechanisms of inheritance and the deeper nature of life's evolution and variety.
Even readers who lack a background in science and philosophy will learn a tremendous amount from this engaging narrative. The book elucidates DNA's relationship to health and the... View Details
Move Your DNA: Restore Your Health Through Natural Movement Expanded Edition
by Katy Bowman (Author)
Humorous, fascinating, and science based, the bestselling first edition of Move Your DNA has been updated and expanded to include a comprehensive three-level exercise program.
In layperson-friendly terms Move Your DNA addresses the vast quantities of disease we are suffering from, identifying our lack of movement as the primary cause. Readers can use the corrective exercises and lifestyle changes Katy Bowman has created to help each of us transition to healthy, naturally moving bodies. Move Your DNA explains the science behind our need for natural movement right down... View Details
The DNA of Relationships
by Gary Smalley (Author)
“Life is relationships; the rest is just details.” We are designed for relationships, yet they often bring us pain. In this paradigm-shifting book, Dr. Gary Smalley unravels the DNA of relationships: We are made for three great relationships―with God, others, and ourselves―and all relationships involve choice. Gary exposes a destructive relationship dance that characterizes nearly every relationship conflict, and he offers five new dance steps that will revolutionize relationships. The DNA of Relationships, the cornerstone book in Gary Smalley's relationship campaign, will help you... View Details
The Innovator's DNA: Mastering the Five Skills of Disruptive Innovators
by Jeff Dyer (Author), Hal Gregersen (Author), Clayton M. Christensen (Author)
A new classic, cited by leaders and media around the globe as a highly recommended read for anyone interested in innovation.
In The Innovator’s DNA, authors Jeffrey Dyer, Hal Gregersen, and bestselling author Clayton Christensen (The Innovator’s Dilemma, The Innovator’s Solution, How Will You Measure Your Life?) build on what we know about disruptive innovation to show how individuals can develop the skills necessary to move progressively from idea to impact.
By identifying behaviors of the world’s best innovatorsfrom leaders at Amazon and... View Details
DNA Science: A First Course, Second Edition
by David Micklos (Author), Greg Freyer (Author)
This is the second edition of a highly successful textbook (over 50,000 copies sold) in which a highly illustrated, narrative text is combined with easytouse thoroughly reliable laboratory protocols. It contains a fully uptodate collection of 12 rigorously tested and reliable lab experiments in molecular biology, developed at the internationally renowned Dolan DNA Learning Center of Cold Spring Harbor Laboratory, which culminate in the construction and cloning of a recombinant DNA molecule. Proven through more than 10 years of teaching at research and nonresearch colleges and universities,... View Details
DNA (Science Readers: Content and Literacy)
by Teacher Created Materials;Wendy Conklin (Author)
DNA is known as the blueprint for life! Found in every cell of every living thing, DNA strands are packed inside a cell’s nucleus carrying instructions and genetic information. Climb the double helix ladder and crack the DNA code in this fact-filled life science book to explore genetics and why parts of you may appear identical to your great, great, great grandparent. Fifth-grade readers will learn about DNA structure and replication, proteins and genes, chromosomes, inherited traits and alleles, cloning, and more through this high-interest informational text filled with vibrant... View Details
DNA: The Secret of Life
by James D. Watson (Author)
James Watson, the co-discoverer of the structure of DNA and author of the international bestseller The Double Helix, tells the story of the amazing molecule since its discovery fifty years ago, following modern genetics from his own Nobel prize-winning work in the fifties to today's Dolly the sheep, designer babies and GM foods. Professor Watson introduces the science of modern genetics, along with its history and its implications, in this magnificent guide to one of the most triumphant achievements of human science. View Details