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，采用了一个复杂的运输网络，其中的生物分子成分形成了道路和车辆。在非常不确定的环境下，传输具有显著的鲁棒性。本提案的主要目标是了解生物学是如何实现这种功能的，并利用这些知识来实现微米尺寸货物的有效工程运输机制。实现能够同时传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。由于生物分子成分通常在几十纳米尺度上，因此在纳米尺度上探索其机制是一个关键的挑战。解决这些挑战的主要工具来自工程角度，并受到生物学现有见解的指导。该提案将把工程学和生物学的研究人员聚集在一起，为学生提供一个综合的环境。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，这些发现有可能揭示导致受损运输的原因。强大的基础设施能够同时传输许多微米和更小尺寸的颗粒，这将对医学、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艰巨挑战阻碍了在微观尺度上实现强大和高效的运输系统。在生物细胞运输的激励下，这项工作提出了一种强大而高效的工程基础设施，用于使用生物结构运输微米/分子尺度的货物。为了探测和控制交通网络，该提案分别设想了全球和局部尺度上的粗分辨率和精细分辨率目标的策略。在精细的监视和控制尺度上，必须共享稀缺和昂贵的物理资源，如高分辨率传感器，以对多个载体进行询问/控制。在本提案中，将开发联合控制，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。现代控制视角是管理多目标的基本策略。在全球范围内，将对整个交通进行监测，以获得对交通模式的实时和离线推断。建立动态识别和跟踪载体群及其重要性的相关原理。这种物理元素的分类及其重要性将决定计算资源的动态分配。对权衡的相关研究将指导计算资源分配和物理元素信息收集的综合策略。将开发基于图拓扑重建的方法，以达到适合于交通基础设施动态相关时间轨迹的推断。提出的研究具有变革性，因为它将在细胞尺度上实现新的运输范式，这也将为细胞内运输提供独特的见解，从而有可能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.