Collaborative Research: IDR-Engineering of a Novel Nanostructure for Biomedical Sensing and Imaging

0933782/0933415/0933384莫塔梅迪/戈沃洛夫/科托夫免疫衰老是与年龄增长相关的免疫失调的复杂过程。在人类中，随着年龄的增长，免疫力下降表现为对病毒和细菌感染的易感性增加，潜伏病毒重新激活，以及对疫苗的反应减少。众所周知，适应性免疫系统，如T细胞和B细胞，随着年龄的增长而逐渐退化。细胞因子是一种分泌型调节蛋白，在控制细胞存活、生长、分化和功能方面发挥着重要作用。多学科和三机构的“联系合作研究-跨学科建议”汇集了几个具有广泛专业知识和研究兴趣的研究小组，以进行实验和理论研究，目的是设计用于细胞因子传感和高分辨率成像的新型纳米结构。由科托夫博士领导的密歇根大学团队将开展该项目的材料和纳米技术方面的工作，而由莫塔梅迪博士领导的德克萨斯大学医学分部的研究将集中在这项工作的成像和蛋白质组学方面。这些小组的实验工作将得到俄亥俄大学戈沃洛夫博士的理论和建模工作的补充，戈沃罗夫博士将开发能够预测传感器反应的模型。具体地说，他们提出了一种新的传感纳米技术来成像巨噬细胞的细胞因子梯度，用于天然免疫系统的免疫衰老研究。在这项提议分配的未来三年内成功展示具有细胞因子依赖的频移的多功能NW超结构将建立一个用于检测和成像各种细胞因子的概念和方案，同时提供一个独特的机会来表征不同年龄组巨噬细胞的各种细胞因子的分泌，并为设计用于检测和成像各种蛋白质的新型光学传感器奠定基础。更广泛的影响拟议的工作本质上是多学科的。该项目结合了新材料、成像、生物工程、生物物理学和建模以及蛋白质组学方面的专业知识。从教育的角度来看，PI和研究生将沉浸在一个高度多样化的环境中，学习与几个不同科学和工程领域的专业人员进行有效的互动和沟通。将特别重视为本科生和少数族裔提供研究机会。NSF的跨学科研究(IDR)计划的目标和范围似乎与拟议的研究完全匹配。拟议的多学科团队的共同努力将创造一个强大的工具，用于基本了解细胞生物学，描述许多疾病的蛋白质组学，临床诊断与细胞分泌相关的疾病，并利用新型光学传感器利用高分辨率成像技术检测和监测小分子(如细胞因子)的空间和时间分布，从而在组织工程中合理控制细胞分化。拟议的研究结合了以下人员的协同活动：一名具有材料科学、纳米技术、纳米光子学和传感专业知识的化学家和工程师(密歇根大学科托夫博士)，一支专门从事细胞和生物医学成像的生物工程团队，与蛋白质组和炎症反应领域的国际知名专家(莫塔梅迪博士及其在UTMB的合作者)合作的生物工程团队，以及一名在复杂纳米结构及其行为建模方面专业的生物物理学家和建模师。拟议的联合努力将极大地促进多个工程和生命科学领域的基础知识，包括传感、成像和蛋白质组学，如果成功，可能对医疗保健和我们的国家需求产生巨大的长期影响。

0933782/0933415/0933384 Motamedi/Govorov/Kotov Immunosenescence is the complex process of immune disregulation associated with advancing age. In humans, the compromised immunity with aging is realized in an increased susceptibility to viral and bacterial infections, reactivation of latent viruses, and decreased responses to vaccines. It is well known that the adaptive immune system such as T and B-cell progressively deteriorate with advancing age. Cytokines are secreted regulatory proteins and play vital roles in controlling cell survival, growth differentiation and function. The multi-disciplinary and tri-institutional "Linked Collaborative Research- Interdisciplinary Proposal" brings together several research groups with broad expertise and research interest to conduct experimental and theoretical studies aimed at engineering of novel nanostructures for sensing and high resolution imaging of cytokines. The group at the University of Michigan lead by Dr. Kotov will carry out the materials and nanotechnology aspect of this project, while the investigation at the University of Texas Medical Branch lead by Dr. Motamedi will concentrate on imaging and proteomics of this work. The experimental efforts of these groups will be complemented by the theoretical and modeling efforts of Dr. Govorov at Ohio University who will be developing models capable of predicting the response of the sensors. Specifically, they propose a novel sensing nanotechnology to image cytokines gradient of macrophages for the immunosenescence study of innate immune system. Successful demonstration of the versatile NW superstructure with cytokine-dependent frequency shift during the next three years allocated for this proposal will establish a concept and protocol for sensing and imaging of various cytokines while providing a unique opportunity to characterize the secretion of various cytokines from different age groups of macrophages, and developing the fundamental foundation for engineering of a new class of optical sensor for detection and imaging of various proteins. Broader Impact The proposed work is inherently multidisciplinary. The project combines expertise in new materials, imaging, bioengineering, biophysics and modeling as well as proteomics. From educational point of view, PIs, and graduate students will be immersed into a highly diverse environment, learning to interact and communicate effectively with professionals in several different fields of science and engineering. Special attention will be given to providing research opportunities to undergraduates and minority. The goals and scope of the interdisciplinary research (IDR) program at NSF appear to be an exact match for the proposed research. The joint efforts of the proposed multi-disciplinary team will create a powerful tool for the fundamental understanding of cell biology, characterization of proteomics of many diseases, clinical diagnosis of cell-secretion related diseases and the potential for rational control of cell differentiation in tissue engineering using novel optical sensors to detect and monitor the spatial and temporal distribution of small molecules such cytokines using high resolution imaging techniques. The proposed research combines the synergistic activities of a chemist and engineer with expertise in material sciences, nanotechnology, nanophotonics and sensing (Dr. Kotov, U of M), a bioengineering team specializing in cellular and biomedical imaging working with internationally known expert in the area of proteomics and inflammatory responses (Dr. Motamedi and his collaborators at UTMB) and a biophysicist and modeler with expertise in modeling of complex nanostructure and their behavior. The proposed joint efforts will significantly advance fundamental knowledge in multiple engineering and life science areas, including sensing, imaging and proteomics and if successful could have enormous long-term impact on health care and our national needs.