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

免疫衰老是与年龄增长相关的复杂的免疫失调过程。在人类中，随着年龄的增长，免疫力的降低体现在对病毒和细菌感染的易感性增加，潜伏病毒的重新激活以及对疫苗的反应降低。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性调节蛋白，在控制细胞存活、生长分化和功能等方面起着重要作用。多学科和三机构的“关联合作研究-跨学科提案”将几个具有广泛专业知识和研究兴趣的研究小组聚集在一起，进行旨在用于细胞因子传感和高分辨率成像的新型纳米结构工程的实验和理论研究。由Kotov博士领导的密歇根大学小组将开展该项目的材料和纳米技术方面的研究，而由Motamedi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。俄亥俄大学的Govorov博士将开发能够预测传感器反应的模型，并将对这些小组的实验工作进行理论和建模工作的补充。具体来说，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，用于先天免疫系统的免疫衰老研究。在接下来的三年里，成功展示具有细胞因子依赖频移的多功能NW上层结构将为各种细胞因子的传感和成像建立一个概念和方案，同时提供一个独特的机会来表征来自不同年龄段巨噬细胞的各种细胞因子的分泌。并为一种新型的用于检测和成像各种蛋白质的光学传感器的工程设计奠定了基础。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士进行有效的互动和沟通。将特别注意为本科生和少数民族提供研究机会。NSF跨学科研究（IDR）项目的目标和范围似乎与提议的研究完全匹配。该多学科团队的共同努力将为细胞生物学的基础理解，许多疾病的蛋白质组学表征，细胞分泌相关疾病的临床诊断以及组织工程中合理控制细胞分化的潜力创造一个强大的工具，使用新型光学传感器来检测和监测小分子如细胞因子的空间和时间分布，使用高分辨率成像技术。拟议的研究结合了化学家和工程师在材料科学，纳米技术，纳米光子学和传感方面的专业知识的协同活动（Kotov博士，密歇根大学），一个专门从事细胞和生物医学成像的生物工程团队，与蛋白质组学和炎症反应领域的国际知名专家（Motamedi博士和他在UTMB的合作者）和一个生物物理学家和建模师在复杂纳米结构及其行为建模方面的专业知识合作。拟议的联合努力将大大提高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，将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.