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跨学科研究计划，该计划将结合纳米材料，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。该K99/R00应用程序具有两个组件，可以帮助我实现目标：1）在研究级别上，它概述了开发Proteoglycans功能性纳米级Mimetics的策略，一类细胞功能调节剂以及它们集成到微阵列发现平台中，以生成生物医学使用的材料。 2）本应用程序的培训部分描述了我将要采取的步骤，以获取分子和细胞生物学，纳米影像以及专业和职业发展的必要技能，我将需要构建这样的跨学科研究计划并启动作为独立科学家和学者的成功职业。 R00奖将为我的团队提供重要的启动支持，而我们建立了本应用程序中概述的研究项目。当我们寻求未来的研究支持时，我们将在该奖项的帮助下生成的初步数据至关重要。背景：我的学术和研究经验使我有好处，可以开发本应用程序中概述的跨学科研究计划。我的研究生研究的重点是新的化学反应的发展以及这些转化在复杂有机分子构建中的应用。作为博士后研究员，我使用了合成技能来创建用于微阵列应用的细胞表面糖蛋白的新纳米级模拟物。在这项工作中，我熟悉碳水化合物和聚合物合成，微阵列制造以及许多用于表面和软纳米材料表征的方法。此外，我还帮助建立并在分子铸造厂建立了一个合成实验室，当我开始自己的研究实验室时，为未来获得了宝贵的经验。研究：附带的研究提案概述了蛋白聚糖的纳米级替代物（我称其为“ neopgs”）及其用作组织工程脚手架中的细胞功能调节剂，作为早期癌症检测的成像剂，作为早期癌症检测的成像剂，以及作为纳米晶体生长和nanocrystal Grenentples的新型型型分子模板。蛋白聚糖在生物体中执行所有这些功能；但是，迄今为止，利用其独特功能用于医疗目的是具有挑战性的。它们的结构复杂性，组成和功能异质性以及非塑料生物合成限制了它们在生物医学研究中的适用性。我的建议概述了一种简单的合成策略，该策略将负责蛋白聚糖的生物学功能的基本建筑特征转化为纳米级聚合物NEOPGS。利用微阵列的技术力量以及我在建造它们方面的技能，我的团队将构建一个“ Neopg芯片”，以迅速询问NEOPG结构库，以便其发挥理想的生物学特性。在三个特定的项目中，我们将展示Neopgs的广泛效用及其生物医学研究的潜力。培训：在我过渡到我学术生涯的独立阶段期间，该奖项的K99培训部分至关重要。我打算追求的研究的生物医学重点必须使我精通分子和细胞生物学的主题和技术。在Bertozzi教授的指导下拟议的培训将帮助我获得这些技能。我将通过与Molecular Foundry的James de Yoreo合作获得的纳米影像技术，将使我的研究团队能够设计与生物构建块的维度相匹配的材料，并探索新的方法来设计生物界面。通过LBNL和UC Berkeley获得的众多专业和职业发展资源以及我的出色指导委员会由分子生物学，生物材料，纳米科学和组织工程专家组成，而我在美国和我开展自己的独立职业的同时，将是一项无价的资产。环境：作为Bertozzi实验室的成员，我将可以使用分子铸造厂的最先进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和多样性，其对化学和分子生物学领域的高影响力贡献的良好记录以及她小组中的Bertozzi养育者教授的高度协作氛围将促进我在分子和细胞生物学培训方面的快速进步。在我接受纳米材料成像和表征的培训时，与分子铸造厂与James Deyoreo博士的合作将提供重要的支持。最后，加州大学伯克利分校著名的学术和科学界提供了一个充满活力的环境，在该环境中，交换思想，建立合作和探索科学领域的新领域，无疑会为我的职业发展做出贡献。