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

计算革命始于两千多年前，当时出现了计算天体运动的机械装置。几个世纪后，精密的发条自动机被开发出来，用于控制推动工业革命的机械，最终以巴贝奇设计的可编程机械计算机而告终。随着上个世纪的电子革命，计算机的速度和复杂性急剧增加。现在，我们使用嵌入式计算机为大量机电设备的行为编程，从手机和卫星到工业制造机器人和自动驾驶汽车。计算的历史教会了研究人员两件事：第一，计算原理可以体现在从齿轮到晶体管的各种各样的物理基材上；第二，掌握一种新的计算物理基材有可能改变技术。另一场革命刚刚开始，它的灵感来自于生命中不可思议的化学和分子机制，它的物理计算基础由合成的生物分子和设计的化学反应组成。就像之前的革命一样，这次“分子编程革命”将以计算机科学的原理为核心。通过系统地编程一系列复杂的基于信息的分子系统的行为，从决策电路和分子尺度制造到生物医学诊断和智能治疗，它有可能从根本上改变材料、化学、生物和医疗行业。随着分子编程的发展，化学将成为21世纪重要的新型信息技术。这个计算机探险项目旨在为分子编程建立坚实的基础。基于DNA纳米技术、DNA计算和合成生物学的进步，该项目将开发DNA链的可编程自组装方法，以创建复杂的2D和3D结构，基于DNA、RNA和蛋白质之间可编程相互作用的动态生化电路，以及空间组织分子系统和活细胞内的综合行为。这些架构将为创建可编程分子系统提供系统化的构建模块，这些系统能够感知分子输入，计算这些输入的决策，并对其环境采取行动。为了管理系统的复杂性并提供模块化，该项目将建立抽象层次结构，其中包含用于编程结构和行为的相关高级语言，将高级代码转换为可合成DNA序列列表的编译器，以及可以预测序列性能的分析软件。这将允许分子编程人员在实验室合成之前指定、设计和验证其系统的正确性。除了这些软件工具外，该项目还将研究分子算法理论，以了解基于信息的分子系统的潜力和局限性，是什么使它们在执行任务时高效，以及如何有效地设计和分析它们。将这一基础研究的产品投入测试，该项目将追求现实世界的应用，如用于探测生物系统的分子仪器和纳米级设备的可编程制造。该项目将通过建立一个由学生、教师、研究人员、科学家和工程师组成的多元化社区，扩大从事分子编程的科学家和工程师的网络。这个社区将通过创建可公开访问的软件工具、课程、教科书、研讨会、教程、本科生研究竞赛和科普视频来培养，以教授分子编程的原理和方法，并吸引年轻的研究人员和公众参与这个令人兴奋的新领域。与相关生物技术和其他高科技公司的工业伙伴关系将确保知识迅速转化为现实世界的产品。也许最重要的是，随着分子编程成为一种广泛应用的技术，它有可能用新的复杂纳米结构材料改变工业，用综合和自主控制的反应改变化学，用先进的分子仪器改变生物学，用更复杂的诊断和治疗改变医疗保健。

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.