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

细胞，执行许多重要的功能，使用一个精心设计的运输网络与生物分子组成部分形成道路以及车辆。在非常不确定的环境下，实现了显着的鲁棒性的运输。该提案的主要目标是了解生物学如何实现这种功能，并利用这些知识实现微米级货物的有效工程运输机制。实现能够同时运输许多微米和更小尺寸颗粒的强大基础设施将对医学，药物开发，电子和生物材料等广泛领域产生变革性影响。这里的一个关键挑战是经常在纳米尺度上探测机制，因为生物分子组分是在几十纳米尺度上。解决这些挑战的主要工具来自工程学的角度，该角度以生物学的现有见解为指导。 该提案将汇集来自工程和生物学的研究人员，为学生提供一个综合环境。此外，众所周知，受损的运输机制可能是许多神经退行性疾病的基础，并且由于这里的研究涉及研究细胞内运输，因此发现有可能揭示导致运输受损的原因。能够同时运输许多微米和更小尺寸颗粒的强大基础设施将对医学，药物开发，电子和生物材料等广泛领域产生变革性影响。 来自潜在的高度不确定和复杂环境的巨大挑战阻碍了在微观尺度上建立强大和高效的运输系统。受生物细胞中运输的启发，这项工作提出了一种强大而有效的工程基础设施，用于使用生物构建体运输微米/分子级货物。为了探测和操纵传输网络，该提案设想了分别在全球和局部尺度上的粗分辨率和细分辨率目标的策略。在监测和控制的精细尺度上，必须共享诸如高分辨率传感器之类的稀缺且昂贵的物理资源以用于多个载波的询问/控制。在这个建议中，联合控制，传感器分配和调度资源，以实现高分辨率探测工具的性能增强的目标的原则，将开发。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，整个交通将被监测，以达到实时和离线的交通模式的推断。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。这种对物理元素及其重要性的分类将决定计算资源的动态分配。相关的权衡研究将指导一个综合战略分配的计算资源和收集信息的物理元素。将开发基于图拓扑结构重构的方法，以实现适合于交通基础设施动态相关时间轨迹的推断。这项研究是变革性的，因为它将在细胞规模上实现一种新的运输模式，这也将为细胞内运输提供独特的见解，在这种情况下，可以在相同的实验条件下研究多种因素。

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.