ITR/RC: Self-Assembly of DNA Nano-Scale Structures for Computation Report thru Dec 31, 2002 (1) Participants: (1.1)Principal Investigators: PI: John H. Reif (leader of research project) Title: Professor Surface address: D223 LSRC, Duke Univ., Durham, NC 27708-0129 Phone number: 919-660-6568 Fax number: 919-660-6519 Email address: [email protected] Homepage URL: www.cs.duke.edu/~reif/HomePage.html Papers in DNA Nanostructures: http://www.cs.duke.edu/~reif/vita/topics/biomolecular.html Project URL: http://www.cs.duke.edu/~reif/BMC Project Report URL: http://www.cs.duke.edu/~reif/BMC/reports/NSF.NANO.ITR.report/NSF.NANO.ITR.rep ort.html Natasha Jonoska Title: Associate Professor Surface address: Department of Mathematics, University of South Florida, 4202 E. Fowler Av., PHY 114, Tampa Fl, 33620-5700 Phone number: 813-974-9566 Fax number: 813-974-2700 Email address: [email protected] Homepage URL: www.math.usf.edu/~jonoska Project URL: http://www.math.usf.edu/~jonoska/bio-comp Nadrian C. Seeman Title: Professor Surface address: Department of Chemistry, New York University, New York, NY 10003 Phone number: 212-998-8395 Fax number: 212-260-7905 Email address: [email protected] Homepage URL: http://seemanlab4.chem.nyu.edu/ Project URL: http://seemanlab4.chem.nyu.edu/nanotech.html (1.2) Collaborating Scientists: Research Assistant Professors: Thom LaBean Title: Research Assistant Professor Surface address: D230 LSRC, Duke University, Durham, NC 27708-0129 Phone number: 919-660-6553 Fax number: 919-660-6519 Email address: [email protected] Homepage URL: www.cs.duke.edu/~thl Hao Yan Title: Research Assistant Professor Surface address: D230 LSRC, Duke University, Durham, NC 27708-0129 Phone number: 919-660-6553 Fax number: 919-660-6519 Email address: [email protected] Homepage URL: http://www.cs.duke.edu/~hy1 Training and Development The PI and subcontract PIs have trained numerous Postdoctoral Assistants in the techniques of DNA nanotechnology and DNA-based computation. These people are among the few individuals in the world possessing these skills. We expect that they will be successful in using these methods in their future careers. (1.3) Postdoctoral Assistants: Duke Postdoctoral Assistants supervised by John Reif: Xiaoju Guan (jointly supervised with Hao Yan), 2003-current Sang Jung Ahn (jointly supervised with Thom LaBean), 2003- current Dage Liu, Research Associate http://www.cs.duke.edu/~liu , 2002- current Prior Duke Postdoctoral Assistants: Hao Yan, 2001-2002 (currently Research Assistant Professor, CS Dept, Duke University www.cs.duke.edu/~thl/) Thom LaBean, 1998-2001 (currently Research Assistant Professor, CS Dept, Duke University http://www.cs.duke.edu/~hy1/) NYU Postdoctoral Assistants supervised: Lisa Wenzler Savin Yariv Pinto (1.4) Graduate students: The PI and subcontract PIs have trained and graduated numerous graduate students in the techniques of DNA nanotechnology and DNA-based computation. These people are among the few individuals in the world possessing these skills. We expect that they will be successful in using these methods in their future careers. Duke University Graduate Students supervised by John Reif: (Ph.D. candidates) Zhung(Robert) Sun, Ph.D. thesis topic: Complexity of Robotic Movement Problems. Projected Date of Graduation: Spring 2002. Tingting Jiang, Ph.D. thesis topic: Molecular simulation algorithms and nonuniform randomized path planning. Projected Date of Graduation: Spring '2004. Peng Yin, Ph.d thesis topic: DNA Nanorobotics. Projected Date of Graduation: Spring '2004. Sung Ha Park (jointly supervised with Thom LaBean and Gleb Finkelstein, Dept of Physics), Ph.D. thesis topic: Conductivity of Metalized DNA Nanostructures. Projected Date of Graduation: Spring '2004. Hanging Li (jointly supervised with Hao Yan and Dan Kenan, Medical School), Ph.D. thesis topic: Laboratory Demonstration of Molecular Robotics. Projected Date of Graduation: Spring '2004. Duke University Graduate Student Supervision (Completed Degrees): Guo Bo, Master Thesis “Computing by DNA Self-Assembly”. Oct, 2001 (currently Research Scientist, Mitsubishi Electric, Japan). Yuan Guangwei, Master Thesis “Simulation of DNA Self-Assembly”, Fall 2000 (currently Research Scientist, China). Christopher Butler, Master Thesis “Simulations of Molectronics architectures”, 2000. May 2000, Xavier Berni: MS Thesis, DNA tagging. NYU Graduate Student Supervision by Ned Seeman(NYU): NYU Postdoctoral Assistants supervised: Lisa Wenzler Savin Yariv Pinto NYU Graduate students supervised: Pamela Constantinou Hao Yan Phiset Sa-Ardyen Baoquan Ding Xiaoping Yang Furong Liu Roujie Sha Chengde Mao Weiqiong Sun Zhiyong Shen Hao Yan Natasha Jonoska (USF): USF PhD graduate students current: Kalpana Mahalingam (projected graduation 2003) Danieal Filipov (projected graduation 2003) Joni Pirno (starting) David Kephart (starting) (2) Major Project Activities and Findings (2.1) Major research and education ACTIVITIES: Summary of Goals. This research is a collaboration between: John Reif at Duke University (PI), Nadrian Seeman at New York University, and Natasha Jonoska at the University of South Florida. The overall goal was to develop and demonstrate DNA self-assembly to do massive parallel computing at the molecular scale. This involves the development of experimental proof- of-concept demonstrations of the application of DNA self-assembly to various basic computational tasks, such as sequences of arithmetic and logical computations executed in massively parallel fashion, and the application of this method to hard computational problems such as integer factorization. Ongoing research includes the development of novel DNA tiles with properties that facilitate the self-assembly and their visualization by imaging devices such as atomic force microscopes and electron microscopes, the testing of various input/output methods, and methods to minimize errors in self- assembly. The self assembly of junction molecules and construction of three dimensional structures such as graphs Overview of computation by DNA self-assembly. DNA self-assembly is a methodology for the construction of molecular scale structures. In this method, artificially synthesized single stranded DNA self-assembles into DNA crossover molecules (tiles). These DNA tiles have sticky ends that preferentially match the sticky ends of certain other DNA tiles, facilitating the further assembly into tiling lattices. The self-assembly of large 2D lattices consisting of up to thousands of tiles have been recently demonstrated by Seeman and Winfree. DNA self-assembly can, using only a small number of component tiles, provide arbitrarily complex assemblies. It can be used to execute computation, using tiles that specify individual steps of the computation. In this emerging new methodology for computation: (i) input is provided by sets of single stranded DNA that serve as nucleation sites for assemblies, and (ii) output can be made by the ligation of reporter strands of DNA that run though the resulting assembly, and then released by denaturing. Moreover, DNA self-assembly can be executed in massively parallel fashion, with concurrent assemblies that may execute computations independently. Due to the very compact form of DNA molecules, the degree of parallelism (due to distinct tiling assemblies) may be 1016 or possibly 018. In the case of junction molecules and 3D structures, the output is the graph structure itself, since the coding of the problem is such that the solution exists iff the structure is assembled. For surveys of recent work in this area see: J. H. Reif, Molecular Assembly and Computation: From Theory to Experimental Demonstrations, plenary paper, 29-th International Colloquium on AutomataLanguages, and Programming(ICALP), Málaga, Spain (July 8, 2002). J.H. Reif, T.H. LaBean & N.C. Seeman, Challenges and Applications for Self-Assembled DNA Nanostructures, Sixth International Workshop on DNA-Based Computers, DNA 2000, Leiden, The Netherlands, (June, 2000) ed. A. Condon, G. Rozenberg. Springer- Verlag, Berlin Heidelberg, Lecture Notes in Computer Science 2054, 173-198, (2001). T.H. LaBean (in press, 2003) “Introduction to Self-Assembling DNA Nanostructures for Computation and Nanofabrication”. in CBGI 2001, Proceedings from Computational Biology and Genome Informatics, held 3/2001 Durham, NC, World Scientific Publishing. Talk Slides: J. H. Reif, DNA Lattices: A Programmable Method for Molecular Scale Patterning and Computation, special issue on Bio-Computation, Computer and Scientific Engineering Magazine, IEEE Computer Society. February 2002, pp 32-41. For more details, see: J.H. Reif, T.H. LaBean, and N.C. Seeman, “Challenges and Applications for Self- Assembled DNA Nanostructures,” Proc. Sixth International Workshop on DNA-Based Computers, DIMACS Series in Discrete Mathematics and Theoretical Computer Science, Edited by A. Condon and G. Rozenberg. Lecture Notes in Computer Science, Springer- Verlag, Berlin Heidelberg, vol. 2054, 2001, pp. 173-198:. Summary of Research Activities. We are developing new methods for nano-assembly of computational structures. The nano-structures constructed consist of DNA crossover molecules (tiles) that have sticky ends that match the sticky ends of other DNA tiles. The DNA tiles self assemble into large lattices that can execute computations. We are executing experimental tests of computation by self-assembly of DNA nanostructure tilings. The key advantage of this approach was that the self-assembly sidesteps time consuming laboratory steps required by other