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：
8286932
负责人：
Kamil Godula
金额：
$ 8.23万
依托单位：
UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8286932
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 Health 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 Screening procedure 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 bioimaging biomineralization calcification cancer cell carbohydrate binding protein career career development chemical reaction college density design experience forging frontier instrumentation member mimetics molecular recognition nanocomposite nanocrystal nanoimaging nanomaterials nanometer nanoscale nanoscience neglect nerve supply neurogenesis novel novel diagnostics novel therapeutics planetary Atmosphere programs rapid technique scaffold skills stem cell differentiation sulfation tissue regeneration tissue support frame tool tumor

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：我的职业目标是在美国一所主要大学领导一个跨学科研究项目，该项目将结合纳米材料、组织工程和生物成像研究的组成部分，以创建新的治疗和诊断工具。这个 K99/R00 应用程序有两个部分可以帮助我实现我的目标：1) 在研究层面，它概述了开发蛋白聚糖（一类细胞功能调节剂）的功能性纳米级模拟物以及将其集成到微阵列中的策略生成生物医学用途材料的发现平台。 2) 本申请的培训部分描述了我将采取的步骤，以获得分子和细胞生物学、纳米成像以及专业和职业发展方面的必要技能，我将需要建立这样一个跨学科研究项目，并作为独立的人开启成功的职业生涯科学家和学者。 R00 奖将为我的团队提供重要的启动支持，同时我们将建立本申请中概述的研究项目。我们在该奖项的帮助下生成的初步数据对于我们寻求未来的研究支持至关重要。背景：我的学术和研究经验使我能够很好地开发本申请中概述的跨学科研究项目。我的研究生研究重点是新化学反应的开发以及这些转化在复杂有机分子构建中的应用。作为一名博士后研究员，我利用自己的合成技能为微阵列应用创建了一种新型细胞表面糖蛋白纳米级模拟物。在这项工作中，我熟悉了碳水化合物和聚合物合成、微阵列制造以及多种表面和软纳米材料表征方法。此外，我还帮助在分子铸造厂建立并运营了一个合成实验室，为我未来建立自己的研究实验室获得了宝贵的经验。研究：所附研究提案概述了蛋白聚糖纳米级替代物（我称之为“neoPG”）的设计及其在组织工程支架中作为细胞功能调节剂、作为早期癌症检测的成像剂以及作为纳米晶体生长的新型大分子模板的用途和纳米复合材料组装。蛋白多糖在生物体中执行所有这些功能；然而，迄今为止，将其独特的能力用于医疗目的仍然具有挑战性。它们的结构复杂性、组成和功能异质性以及非模板生物合成限制了它们在生物医学研究中的应用。我的提案概述了一种简单的合成策略，将负责蛋白聚糖生物功能的基本结构特征转化为纳米级聚合 NeoPG。利用微阵列的技术力量以及我构建它们的技能，我的团队将构建一个“neoPG芯片”，以快速询问neoPG结构库，以确定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 的广泛实用性及其在生物医学研究中的潜力。培训：该奖项的 K99 培训部分对于我向学术生涯的独立阶段过渡至关重要。我打算从事的研究的生物医学重点要求我精通分子和细胞生物学的主题和技术。贝尔托齐教授指导下的拟议培训将帮助我获得这些技能。我将通过与分子铸造厂的 James De Yoreo 博士合作获得纳米成像技术，这将使我的研究团队能够设计与生物构件尺寸相匹配的材料，并探索设计生物界面的新方法。劳伦斯伯克利国家实验室和加州大学伯克利分校提供的众多专业和职业发展资源以及由分子生物学、生物材料、纳米科学和组织工程专家组成的一流指导委员会将成为我在美国寻求教职的宝贵财富。开启我自己的独立事业。环境：作为 Bertozzi 实验室的成员，我将可以使用分子铸造厂最先进的设施以及加州大学伯克利分校化学学院的资源和仪器。 Bertozzi 研究团队的科学卓越性和多样性、其在化学和分子生物学领域的高影响力贡献的良好记录，以及 Bertozzi 教授在她的团队中营造的高度协作的氛围，将促进我在分子和分子生物学领域的快速进步。细胞生物学培训。当我接受纳米材料成像和表征方面的培训时，与分子铸造厂的 James DeYoreo 博士的合作以及铸造厂科学人员的专业知识将为我提供重要的支持。最后，加州大学伯克利分校著名的学术和科学社区提供了一个充满活力的环境，可以在其中交流思想、建立合作和探索科学新领域，这无疑将有助于我的职业成长。