CPS: Synergy: Collaborative Research: Learning from cells to create transportation infrastructure at the micron scale

细胞为了执行许多重要的功能，使用了一个复杂的运输网络，其中包括形成道路和车辆的生物分子成分。该传输在非常不确定的环境下以显著的健壮性实现。这项提议的主要目标是了解生物如何实现这种功能，并利用这些知识来实现微米级货物的有效工程运输机制。实现能够同时传输许多微米和较小尺寸颗粒的强大基础设施将对医药、药物开发、电子和生物材料等广泛领域产生革命性影响。这里的一个关键挑战是探索机制，通常是在纳米尺度上，因为生物分子成分在几十纳米尺度上。应对这些挑战的主要工具来自工程学观点，该观点以生物学现有的见解为指导。该提案将汇集工程学和生物学的研究人员，并为学生提供一个综合环境。此外，众所周知，转运机制受损可能是许多神经退行性疾病的基础，由于这里的研究涉及细胞内转运，因此发现有可能揭示导致转运受损的原因。能够同时传输许多微米和较小颗粒的强大基础设施将对医药、药物开发、电子和生物材料等广泛领域产生革命性影响。来自高度不确定和复杂的基本环境的严峻挑战阻碍了在微观尺度上实现强大和高效的运输系统。在生物细胞运输的推动下，这项工作提出了一种坚固而高效的工程基础设施，用于使用生物构造运输微米/分子规模的货物。关于探测和操纵运输网络，该提案设想了分别在全球和地方两级实现粗略和精细分辨率目标的战略。在监测和控制的精细规模上，必须共享稀缺而昂贵的物理资源，如高分辨率传感器，以对多个载体进行审问/控制。在这项提案中，将制定联合控制、传感器分配和资源调度的原则，以实现高分辨率探测工具的增强性能目标。现代控制视角形成了管理多个目标的基本策略。在全球范围内，将对整个交通进行监测，以实时和离线地推断交通模式。将建立动态识别和跟踪运营商集群及其重要性的相关原则。对物理要素及其重要性的这种分类将决定计算资源的动态分配。相关的权衡研究将指导分配计算资源和收集有关物理要素的信息的综合战略。将开发基于图拓扑重建的方法，以得出适合于交通基础设施的动态相关时间轨迹的推断。这项拟议的研究具有变革性，因为它将在细胞水平上实现一种新的运输范式，这也将提供对细胞内运输的独特见解，从而有可能在相同的实验条件下调查多种因素。

Cells, to carry out many important functions, employ an elaborate transport network with bio-molecular components forming roadways as well as vehicles. The transport is achieved with remarkable robustness under a very uncertain environment. The main goal of this proposal is to understand how biology achieves such functionality and leveraging the knowledge toward realizing effective engineered transport mechanisms for micron sized cargo. The realization of a robust infrastructure that enables simultaneous transport of many micron and smaller sized particles will have a transformative impact on a vast range of areas such as medicine, drug development, electronics, and bio-materials. A key challenge here is to probe the mechanisms often at the nanometer scale as the bio-molecular components are at tens of nanometer scale. The main tools for addressing these challenges come from an engineering perspective that is guided by existing insights from biology. The proposal will bring together researchers from engineering and biology and it provides an integrated environment for students. Moreover, it is known that an impaired transport mechanism can underlie many neurodegenerative maladies, and as the research here pertains to studying intracellular transport, discoveries hold the potential for shedding light on what causes the impaired transport. Robust infrastructure that enables simultaneous transport of many micron and smaller sized particles will have a transformative impact on a vast range of areas such as medicine, drug development, electronics, and bio-materials. Daunting challenges from the underlying highly uncertain and complex environments impede enabling robust and efficient transport systems at micro-scale. Motivated by transport in biological cells, this work proposes a robust and efficient engineered infrastructure for transporting micron/molecular scale cargo using biological constructs. For probing and manipulating the transport network, the proposal envisions strategies for coarse and fine resolution objectives at the global and local scales respectively. At the fine scale of monitoring and control, scarce and expensive physical resources such as high resolution sensors have to be shared for interrogation/control of multiple carriers. In this proposal, the principles for joint control, sensor allocation and scheduling of resources to achieve enhanced performance objectives of a high resolution probing tool, will be developed. A modern control perspective forms an essential strategy for managing multiple objectives. At the global scale, entire traffic will be monitored to arrive at real-time and off-line inferences on traffic modalities. Associated principles for dynamically identifying and tracking clusters of carriers and their importance will be built. This categorization of physical elements and their importance will determine the dynamic allocation of computational resources. Associated study of trade-offs will guide a combined strategy for allocation of computational resources and gathering of information on physical elements. Methods based on the reconstruction of graph topologies for reaching inferences that are suited to dynamically related time trajectories for the transportation infrastructure will be developed. The research proposed is transformative as it will enable a new transport paradigm at the cellular scale, which will also provide unique insights into intracellular transport where it will be possible to investigate multiple factors under the same experimental conditions.