Thursday, September 29, 2016
Our goal for the summer is to develop a system that autonomously sorts DNA tagged structures. Our base system involves randomly placed DNA tagged cargo on a rectangular DNA origami . One edge of the origami is tagged with goal strands, and the rest of the origami is filled with track strands. The origami is then populated with random walkers that traverse the origami, picking up cargo and dropping them off at the goal. The motion of the walker and cargos will be examined by atomic force microscopy imaging. Bulk behavior of the system, kinetics of walking, and mechanisms of cargo picking up, and cargo dropping off will be analyzed by SPEX experiment.
DNA, which encodes most organisms in nature, is considered as an effective medium for representing and storing information. Noting that a computer can be modeled as a device that can carry out computation to produce desired output data for the given input data, we conclude that finding a way of processing data represented by DNA will lead to establishment of a new computational model, or a DNA computer. In this process, we tried to imitate and recreate nature’s precise and intricate engineering unmatched by the most sophisticated engineering of the mankind.
In fact, many different approaches for DNA computing have been studied in the last decade. One example would be Georg Seelig’s implementation of logic gates using Watson-Crick base pairing and strand displacement between DNA segments that represent different data . Another example is David Soloveichik’s work on chemical reaction networks, where it was shown that chemical reactions can be implemented by a cascade of DNA reactions and that such chemical reaction networks are actually Turing-universal [2,3]. Since all such computation (or data processing) takes place on the molecular scale, this research makes a promising approach to nanotechnology.
However, despite the enormous computational power of such models, they are distinguished from what happens in biology because they are purely computational and rather unintuitive. Recently a group of researchers turned their attention to implementing more visible and intuitive mechanisms, such as robots, using DNA molecules.
Biomolecular robotics is relatively recent research field. Many kinds of walkers are demonstrated to walk on 1-dimensional track , but just a few of them are demonstrated to walk on 2-dimensional track . Even fewer perform specific functions such as transferring god nanoparticle species as cargos while traversing the pathway . This project aims to incorporate both 2-dimensional walking and a specialized function into a DNA-based robot. More specifically, a molecular-scale DNA-based robot will reorganize cargos on 2dimensional fields.
Project Overview: Ultimate goal
Before reorganizing: randomly scattered cargos
After reorganizing: cargos on the goals
Caltech’s 2011 BIOMOD team is pursuing a topic in the former of those fields, seeking to demonstrate a mechanism for the sorting of cargo particles, each tagged with an identifying DNA strand, scattered across a 100x70nm playing field. Our mechanism is based on the cooperation of a number of independent DNA “walkers” that gradually wander around the playing field in a random walk, and specially positioned, cargo-specific goals. When a walker encounters a cargo, it picks it up by binding to its identifying DNA strand, and carries it around as it continues its exploration. The goals associated with a particular cargo retrieve that cargo from courier walkers by binding to the identifying strand in a way that frees the walker to collect more cargo, and prevents the cargo from being picked up again. Over time, this system will sort initially randomly strewn cargos to destinations predetermined by goal placement.a mechanism of simple directed transport potentially useful in many complex systems constructed on origami, such as molecular assembly lines. Our walker design is significant and novel on its own, due to its simplicity and ability to perform a 2-dimensional random walk, and should prove valuable on its own to future DNA robotics projects. More importantly, this project’s overarching principle of a useful result emerging from very simple and independently less useful elements working together is without a doubt vital to the eventual development larger scale DNA robotic systems.
Why is this useful to us?
We see this technology being used effectively in a number of practical applications. The ability to sort on its own has plenty of uses. Additionally, when coupled with other mechanisms, the ability to sort has the possibility to lead to systems that automatically collect and remove byproducts from a reaction, purify a system and condense products into specified locations, and aid in controlled and detailed micro assembly machines. Additionally, our specific implementation of a solution to this problem is universal enough that it can be applied to not only DNA, but anything that can be tagged with a DNA identifier. For these reasons, we believe that this technology is worth developing such that it can be used as a tool by others in their applications.
The last question that remains unanswered in our design is why we chose to work in a primarily 2D walker based format, rather than a 3D diffusion based format. There are two main reasons for this. Selfishly, we conceptually understand the 2d platform better, and would feel more comfortable working with this sort of environment. We consider it more friendly to testing and troubleshooting and easier to visualize and image. Secondly, and more importantly, we feel that the 2D platform has more widespread future applications than its 3d counterpart. We anticipate that systems will become more complicated and more controlled, and that walkers on origami scaffolds are capable of providing this control much better than a 3D diffusion based system would. As such, we are choosing to specifically target a 2d based system, as this is where we would like to see advancement in science. Furthermore, our molecular robot is not limited to reorganizing molecules, and can easily be modified for many tasks that require continuous exploration and information recognition on 2D surface.
-  Lulu Qian and Erik Winfree. A simple DNA gate motif for synthesizing large-scale circuits, Royal Society Interface, 2011
-  David Soloveichik, Georg Seelig and Erik Winfree. DNA as a Universal Substrate for Chemical Kinetics. DNA 14, LNCS 5347: 57-69, 2009
-  David Soloveichik, Matthew Cook, Erik Winfree and Jehoshua Bruck. Computation with Finite Stochastic Chemical Reaction Networks. Natural Computing Feburary, 2008.
-  Ye Tian, Yu He, Yi Chen, Peng Yin, and Chengde mao. A DNAzyme That Walks Processively and Autonomously along a One-Dimensional Track. Angewandte Chemie International EditionVol. 44, 4355-4358, 2005
-  Kyle Lund, Anthony J. Manzo, Nadine Dabby, Nicole Michelotti, Alexander Johnson-Buck, Jeanette Nangreave, Steven Taylor, Renjun Pei, Milan N. Stojanovic, Nils G. Walter, Erik Winfree, and Hao Yan. Molecular Robots Guided by Prescriptive Landscapes. Nature, 206-210, 2010
-  Hongzhou Gu, Jie Chao, Shou-Jun Xiao, Nadrian C. Seeman. A proximity-based programmable DNA nanoscale assembly line. Nature 465, 202–205. 2010
-  Paul W. K. Rothemund. Folding DNA to Create Nanoscale Shapes and Patterns. Nature, 297-302, 2006