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NeoProteoglycans as synthetic materials for regenerative medicine and bioimaging

新蛋白聚糖作为再生医学和生物成像的合成材料

基本信息

批准号：
8916112
负责人：
Kamil Godula
金额：
$ 23.79万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8916112
关键词：
Affect Alzheimer&apos s Disease Amyloid fibers Anabolism Architecture Area Atomic Force Microscopy Award Binding Biochemical Biocompatible Materials Biological Biological Process Biology Biomechanics Biomedical Research Bone Tissue Carbohydrates Cartilage Cell Surface Receptors Cell physiology Cells Cellular biology Chemicals Chemistry Collaborations Communities Complex Crystallization Cues Data Decision Making Development Dimensions Engineering Environment Event Extracellular Matrix Faculty Fluorescence Fostering Future Gene Chips Glycosaminoglycans Goals Growth Growth Factor Heterogeneity Homeostasis Hydroxyapatites Image In Situ Inorganic Sulfates Interdisciplinary Study Laboratories Laboratory Research Lead Libraries Life Ligands Malignant Neoplasms Medical Membrane Glycoproteins Mentors Mentorship Methodology Methods Molecular Molecular Biology Molecular Biology Techniques Molecular Structure Muscle Nanostructures Neuromuscular Junction Organism Osteogenesis Phase Polymers Polysaccharides Positioning Attribute Postdoctoral Fellow Property Protein Engineering Proteins Proteoglycan Regenerative Medicine Research Research Project Grants Research Proposals Resistance Resolution Resources Role Running Science Scientist Screening for cancer Signal Pathway Signal Transduction Specificity Structure Sulfatases Surface Techniques Technology Time Tissue Engineering Tissues Training Translating Tumor Tissue Tumor-Associated Process Universities Unspecified or Sulfate Ion Sulfates Vertebral column Water Work abstracting bioimaging biomineralization calcification cancer cell carbohydrate binding protein career career development chemical reaction college density design experience forging frontier imaging agent instrumentation member mimetics molecular recognition nanocomposite nanocrystal nanoimaging nanomaterials nanometer nanoscale nanoscience neglect nerve supply neurogenesis novel novel diagnostics novel therapeutics professional atmosphere programs rapid technique scaffold screening skills stem cell differentiation sulfation tissue regeneration tissue support frame tool tumor

项目摘要

7. Project Summary and Abstract Overview and Career Goals: My career goal is to lead an interdisciplinary research program at a major US university, which will combine components of nanomaterials, tissue engineering, and bioimaging research to create new therapeutic and diagnostic tools. This K99/R00 application has two components that will help me achieve my goal: 1) At the research level, it outlines a strategy for the development of functional nanoscale mimetics of proteoglycans, a class of cellular function regulators, and their integration into a microarray discovery platform to generate materials for biomedical use. 2) The training portion of this application describes the steps I will take to acquire the necessary skills in molecular and cell biology, nanoimaging, and professional and career development I will need to build such an interdisciplinary research program and launch a successful career as an independent scientist and scholar. The R00 award will provide an important start-up support for my team, while we establish the research projects outlined in this application. The preliminary data we will generate with the help of this award will be vital as we seek future research support. Background: My academic and research experience makes me well positioned to develop the cross- disciplinary research program outlined in this application. My graduate research focused on the development of new chemical reactions and the application of these transformations in the construction of complex organic molecules. As a postdoctoral fellow, I have used my synthetic skills to create a new class of nanoscale mimetics of cell-surface glycoproteins for microarray applications. During this work, I became familiar with carbohydrate and polymer synthesis, microarray fabrication, and a number of methods for surface and soft nanomaterials characterization. In addition, I have helped establish and run a synthetic laboratory at the Molecular Foundry, gaining an invaluable experience for the future, when I start my own research laboratory. Research: The attached research proposal outlines the design of nanoscale surrogates of proteoglycans (which I term "neoPGs") and their use as cellular function modulators in tissue engineering scaffolds, as imaging agents for early cancer detection, and as novel macromolecular templates for nanocrystal growth and nanocomposites assembly. Proteoglycans perform all these functions in living organisms; however, harnessing their unique capabilities for medical purposes has so far proved challenging. Their structural complexity, compositional and functional heterogeneity, and non-template biosynthesis limits their applicability in biomedical research. My proposal outlines a simple synthetic strategy that translates the basic architectural features responsible for proteoglycans' biological function into nanoscale polymeric neoPGs. Taking advantage of the technological power of microarrays, and my skills in building them, my team will construct a "neoPG chip", to rapidly interrogate a library of neoPG structures for their ability to exert desirable biological properties. In three specific projects, we will demonstrate neoPGs' broad utility and their potential for biomedical research. Training: The K99 training component of this award will be critical during my transition to the independent phase of my academic career. The biomedical focus of the research I intend to pursue necessitates that I become proficient in the topics and techniques of molecular and cell biology. The proposed training under the mentorship of Prof. Bertozzi will help me attain these skills. The nanoimaging techniques I will acquire through collaboration with Dr. James De Yoreo at the Molecular Foundry will enable my research team to design materials that match the dimensions of biological building blocks and explore new ways to engineer biological interfaces. The numerous professional and career development resources available through LBNL and UC Berkeley and my stellar mentoring committee assembled from experts in molecular biology, biomaterials, nanoscience, and tissue engineering will be an invaluable asset, while I seek a faculty position in the US and as I launch my own independent career. Environment: As a member of the Bertozzi lab, I will have access to the state-of-the-art facilities at the Molecular Foundry and the resources and instrumentation of UC Berkeley's College of Chemistry. The scientific excellence and diversity of the Bertozzi research team, its well-established record of high-impact contributions to the fields of chemical and molecular biology, and the highly collaborative atmosphere Prof. Bertozzi fosters in her group will facilitate my rapid progress in molecular and cell biology training. Collaboration with Dr. James DeYoreo at the Molecular Foundry and the expertise of the Foundry's scientific staff will provide an important support, as I undertake my training in nanomaterials imaging and characterization. Finally, UC Berkeley's renowned academic and scientific community provides a vibrant environment, in which to exchange ideas, forge collaborations, and explore new frontiers in science and will undoubtedly contribute to my professional growth.

7.项目概要和摘要概述和职业目标：我的职业目标是在美国一个主要的大学领导一个跨学科的研究项目。这所大学将把纳米材料、组织工程和生物成像研究的联合收割机组成部分结合起来，创造新的治疗和诊断工具。此K99/R 00应用程序包含两个组件，实现我的目标：1）在研究层面，它概述了功能纳米级的发展战略蛋白聚糖类细胞功能调节剂的模拟物及其在微阵列中的整合发现平台，以产生生物医学用途的材料。2)本应用程序的培训部分介绍了我将采取的步骤，以获得必要的技能，在分子和细胞生物学，纳米成像，和专业和职业发展，我将需要建立这样一个跨学科的研究计划，并推出一个成功的作为一名独立的科学家和学者。R 00奖将为以下项目提供重要的启动支持：我的团队，同时我们建立了这个应用程序中概述的研究项目。初步数据，我们将在这个奖项的帮助下产生的将是至关重要的，因为我们寻求未来的研究支持。背景：我的学术和研究经验使我能够很好地发展跨学科，本申请中概述的学科研究计划。我的研究生研究集中在新的化学反应及其在构建复杂有机化合物中的应用分子。作为一名博士后，我用我的合成技能创造了一种新的纳米级用于微阵列应用的细胞表面糖蛋白的模拟物。在这段时间里，我逐渐熟悉了碳水化合物和聚合物合成，微阵列制造，以及许多表面和软纳米材料表征此外，我还帮助建立和运行了一个合成实验室，分子铸造，获得了宝贵的经验，为未来，当我开始我自己的研究实验室。研究：所附的研究提案概述了蛋白聚糖的纳米级替代品的设计（我称之为“neoPG”）及其在组织工程支架中作为细胞功能调节剂的用途，用于早期癌症检测的成像剂，以及作为用于肿瘤生长的新型大分子模板，纳米复合材料组装蛋白聚糖在生物体中执行所有这些功能;然而，它们在医疗方面的独特能力迄今证明是具有挑战性的。它们结构的复杂性，组成和功能的异质性，以及非模板生物合成限制了它们在生物合成中的适用性。生物医学研究我的建议概述了一个简单的合成策略，将基本的架构将负责蛋白聚糖生物功能的特征转化为纳米级聚合物neoPG。利用微阵列的技术力量，以及我在构建它们方面的技能，我的团队将构建一个“neoPG”，芯片”，以快速询问neoPG结构库，了解它们发挥所需生物学特性的能力。在三个具体项目中，我们将展示neoPG的广泛用途及其在生物医学研究中的潜力。培训：该奖项的K99培训部分将在我过渡到独立的关键我学术生涯的一个阶段。我打算从事的研究的生物医学重点需要我精通分子和细胞生物学的主题和技术。拟议的培训贝尔托齐教授的指导将帮助我获得这些技能。我将获得的纳米成像技术通过与分子铸造厂的James De Yoreo博士合作，设计与生物积木尺寸相匹配的材料，探索新的工程方法，生物界面通过以下途径提供的众多专业和职业发展资源 LBNL和加州大学伯克利分校以及我的明星指导委员会由分子生物学专家组成，生物材料，纳米科学和组织工程将是一个宝贵的资产，而我寻求一个教师职位，美国和我开始自己独立的职业生涯。环境：作为Bertozzi实验室的一员，我将有机会使用最先进的设施，分子铸造和加州大学伯克利分校化学学院的资源和仪器。的 Bertozzi研究团队的科学卓越性和多样性，化学和分子生物学领域的贡献，以及高度合作的气氛教授。在她的小组中培养的人将促进我在分子和细胞生物学培训方面的快速进步。与James DeYoreo博士在分子铸造厂的合作，以及铸造厂科学专家的专业知识，工作人员将提供重要的支持，因为我在纳米材料成像方面进行了培训，特征化最后，加州大学伯克利分校著名的学术和科学界提供了一个充满活力的环境，在其中交流思想，建立合作，探索新的前沿科学和意志这无疑有助于我的专业成长。