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Award Abstract #1317653

Collaborative Research: Molecular Programming Architectures, Abstractions, Algorithms, and Applications

Division of Computing and Communication Foundations
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Initial Amendment Date: September 17, 2013
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Latest Amendment Date: September 12, 2014
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Award Number: 1317653
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Award Instrument: Continuing grant
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Program Manager: Mitra Basu
CCF Division of Computing and Communication Foundations
CSE Direct For Computer & Info Scie & Enginr
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Start Date: October 1, 2013
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End Date: September 30, 2018 (Estimated)
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Awarded Amount to Date: $2,000,000.00
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Investigator(s): Eric Klavins klavins@ee.washington.edu (Principal Investigator)
Georg Seelig (Co-Principal Investigator)
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Sponsor: University of Washington
4333 Brooklyn Ave NE
Seattle, WA 98195-0001 (206)543-4043
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Program Reference Code(s): 7723
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Program Element Code(s): 1640


The computing revolution began over two thousand years ago with the advent of mechanical devices for calculating the motions of celestial bodies. Sophisticated clockwork automata were developed centuries later to control the machinery that drove the industrial revolution, culminating in Babbage's remarkable design for a programmable mechanical computer. With the electronic revolution of the last century, the speed and complexity of computers increased dramatically. Using embedded computers we now program the behavior of a vast array of electro-mechanical devices, from cell phones and satellites to industrial manufacturing robots and self-driving cars. The history of computing has taught researchers two things: first, that the principles of computing can be embodied in a wide variety of physical substrates from gears to transistors, and second, that the mastery of a new physical substrate for computing has the potential to transform technology. Another revolution is just beginning, one whose inspiration is the incredible chemistry and molecular machinery of life, one whose physical computing substrate consists of synthetic biomolecules and designed chemical reactions. Like the previous revolutions, this "molecular programming revolution" will have the principles of computer science at its core. By systematically programming the behaviors of a wide array of complex information-based molecular systems, from decision-making circuitry and molecular-scale manufacturing to biomedical diagnosis and smart therapeutics, it has the potential to radically transform material, chemical, biological, and medical industries. With molecular programming, chemistry will become a major new information technology of the 21st century.

This Expeditions-in-Computing project aims to establish solid foundations for molecular programming. Building on advances in DNA nanotechnology, DNA computing, and synthetic biology, the project will develop methods for programmable self-assembly of DNA strands to create sophisticated 2D and 3D structures, dynamic biochemical circuitry based on programmable interactions between DNA, RNA, and proteins, and integrated behaviors within spatially organized molecular systems and living cells. These architectures will provide systematic building blocks for creating programmable molecular systems able to sense molecular input, compute decisions about those inputs, and act on their environment. To manage system complexity and to provide modularity, the project will establish abstraction hierarchies with associated high-level languages for programming structure and behavior, compilers that turn high-level code into lists of synthesizable DNA sequences, and analysis software that can predict the performance of the sequences. This will allow molecular programmers to specify, design, and verify the correctness of their systems before they are ever synthesized in the laboratory. In addition to these software tools, the project will study the theory of molecular algorithms in order to understand the potential and limitations of information-based molecular systems, what makes them efficient at the tasks they can perform, and how they can be effectively designed and analyzed. Putting the products of this fundamental research to the test, the project will pursue real-world applications such as molecular instruments for probing biological systems and programmable fabrication of nanoscale devices.

This project will expand the network of scientists and engineers working in molecular programming by building a diverse community of students, teachers, researchers, scientists, and engineers. This community will be fostered through the creation of publicly accessible software tools, courses, textbooks, workshops, tutorials, undergraduate research competitions, and popular science videos to teach the principles and methods of molecular programming and to engage young researchers and the public in this exciting new field. Industrial partnerships with relevant biotechnology and other high-tech companies will ensure fast transfer of knowledge generated into real-world products. Perhaps most importantly, as molecular programming becomes a widespread technology, it has the potential to transform industry with new complex nanostructured materials, to transform chemistry with integrated and autonomous control of reactions, to transform biology with advanced molecular instruments, and to transform health care with more sophisticated diagnostics and therapeutics.


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E. Pierre-Jerome* S. S. Jang*, K. A. Havens, J. L. Nemhauser and E. Klavins. "Recapitulation of the forward nuclear auxin response pathway in yeast," Proceedings of the National Academy of Science, v.111, 2014, p. 9407. 

K. Oishi and E. Klavins. "A Framework for Implementing Finite State Machines in Gene Regulatory Networks," ACS Synthetic Biology, 2014. 

C. Takahashi, A. Miller, F. Ekness, M. Dunham and E. Klavins. "A low cost, customizable turbidostat for use in synthetic circuit characterization," ACS Synthetic Biology, 2014, p. 10.1021/s. 


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