The Small-Number Limit of Biological Information Processing

智力优势：从单细胞到多细胞生物体的各种大小的生物实体都处理能量，例如光能或化学能，用于生长，发育和修复。他们还处理信息，使他们的行为适应环境中不断变化的情况和不断变化的内部状态。例如，细胞必须调整其特定蛋白质的生产以应对其环境的变化，包括来自附近细胞的信号以及来自其自身DNA的新指令。这些反应相当于“生物计算机”的信息处理，这表明我们可以使用信息技术和计算机科学的工具来推进我们对复杂生物系统的理解，只要人类设计的计算机和自然发生的生物系统之间的区别得到尊重。这项研究解决了三个主要的差异点。与当前设计的系统形成直接对比的是，当前设计的系统被设计为最小化噪声，在制造时部署有固定的电路，并且依赖于少量相同的子单元（例如，二维芯片上的晶体管），生物系统似乎：（1）利用噪音，以他们的优势;（2）动态调整他们的处理方法;（3）利用一组异常多样化的潜在机制。在计算机模拟的帮助下，研究人员将推广计算理论中的经典结果，例如电路大小的Shannon-Lyupanov界限，以解释生物学中已知的约束和差异。此外，他们还将把各种各样的实际处理机制纳入数学框架，例如基因表达的平行表观遗传调控，这些机制在大规模实验室研究中不断被发现。这项工作将有助于把过去60年来在计算理论方面所作的巨大投资应用于生物系统的研究。更广泛的影响：预计该项目将产生对广泛的科学和工程受众有用的结果。预计为生物系统的“逆向工程”开发的新算法将适用于其他领域;因此，该项目的一部分资源将专门用于使为提取逻辑结构而开发的技术可供更广泛的社区使用。项目资源还将用于培训和指导新墨西哥州圣达菲研究所的本科生和研究生，该研究所提供独特的、以研究为重点的跨学科教育经验。通过研究所的NSF REU（本科生研究经验）计划和研究生课程的合作者网络招募的学生将在研究人员的指导下进行研究，并在同行评议的文献中发表他们的结果。最后，调查人员将对在新墨西哥州服务不足的农村地区任教的公立学校教师开展外展活动，并接触大量来自STEM领域代表性不足的少数群体的学生。该外展活动将与NSF GUTS（成长思维科学家）项目负责人艾琳·李（Irene Lee）合作进行。在新墨西哥州索科罗的GUTS暑期教师学院，PI将向初中和高中教师介绍生物系统中信息处理的概念，并与他们合作，开发将此内容纳入课程计划，头脑风暴活动和游戏的方法，用于科学课堂。调查人员还将在李的指导下，为参与新墨西哥州超级计算挑战计划的中学生提供指导和辅导。

Intellectual Merit: Living entities of all sizes, from single cells to multi-cellular organisms, process energy, such as light or chemical energy, for use in growth, development and repair. They also process information, adapting their behavior to changing circumstances in their environment and to changing internal states. For example, a cell must adjust its production of specific proteins in response to changes in its environment, including signals from nearby cells, as well as new instructions from its own DNA. These responses amount to information processing by "biological computers," which suggests that we can advance our understanding of complex biological systems using the tools of information technology and computer science, as long as the distinctions between human-designed computers and naturally-occurring biological systems are respected. This research addresses three central points of difference. In direct contrast to current engineered systems, which are designed to minimize noise, are deployed with circuitry fixed at time of fabrication, and rely on a small number of identical subunits (for example, transistors on a two-dimensional chip), biological systems appear to: (1) use noise to their advantage; (2) dynamically adjust their processing methods; and (3) exploit an unusually diverse set of underlying mechanisms. Aided by computer simulations, the investigators will generalize classical results in the theory of computation, such as the Shannon-Lyupanov bounds for circuit size, to account for the constraints and differences known to obtain in biology. In addition they will bring into a mathematical framework the great variety of actual processing mechanisms, such as the parallel epigenetic regulation of gene expression, that are being continuously uncovered in large-scale laboratory investigations. Such work will aid in applying the vast investment made in the theory of computation over the last sixty years to the study of biological systems. Broader Impacts:The project is expected to produce results useful to a wide scientific and engineering audience. It is anticipated that the new algorithms to be developed for the "reverse engineering" of biological systems will be applicable in other domains; therefore, a portion of the project resources is devoted to making techniques developed for the extraction of logical structures available for use by the broader community. Project resources will also be devoted to the training and mentoring of undergraduate and graduate students at the Santa Fe Institute in New Mexico, which provides a unique, research-focused, interdisciplinary educational experience. Students, recruited through the Institute's NSF REU (Research Experiences for Undergraduates) program and through the Investigators' network of collaborators at graduate programs, will conduct research, and publish their results in peer-reviewed literature, under the guidance of the Investigators. Finally, the Investigators will carry out outreach activities to public school teachers who teach in under-served rural areas in New Mexico and reach large numbers of students from minority groups under-represented in STEM fields. The outreach will be conducted in collaboration with Irene Lee, head of the NSF GUTS (Growing Up Thinking Scientifically) program. At the GUTS Summer Teacher Institutes in Socorro, New Mexico, the PI will introduce middle and high school teachers to the concepts of information processing in biological systems and work with them to develop ways to incorporate this content into lesson plans, brainstorming activities and games for use in science classrooms. The Investigators will also, with guidance from Lee, provide mentorship and coaching to secondary students involved in the New Mexico Supercomputing Challenge Program.