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

• 批准号: 8719535
• 负责人: Kamil Godula
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 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/8719535
• 关键词: Affect; Alzheimer' 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; 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; screening; skills; stem cell differentiation; sulfation; tissue regeneration; tissue support frame; tool; tumor

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。项目摘要和摘要 概述和职业目标：我的职业目标是领导美国主要的跨学科研究计划 大学将结合纳米材料，组织工程和生物成像研究的组成部分 创建新的治疗和诊断工具。该K99/R00应用程序有两个组件可以帮助我 实现我的目标：1）在研究层面，它概述了功能性纳米级制定的策略 蛋白聚糖，一类细胞函数调节剂的模拟物及其整合到微阵列中 生成生物医学使用材料的发现平台。 2）该应用程序描述的培训部分 我将采取的步骤获得分子和细胞生物学，纳米影像和专业的必要技能 和职业发展，我需要建立这样的跨学科研究计划并启动成功 作为独立科学家和学者的职业。 R00奖将为 我的团队在我们建立此应用程序中概述的研究项目时。我们将进行初步数据 在我们寻求未来的研究支持时，在该奖项的帮助下生成至关重要。 背景：我的学术和研究经验使我有好处，可以发展交叉 本应用程序中概述了纪律研究计划。我的研究生研究重点是发展 新的化学反应以及这些转换在复杂有机的构建中的应用 分子。作为博士后研究员，我已经使用了合成技巧来创建新的纳米级 用于微阵列应用的细胞表面糖蛋白的模仿。在这项工作中，我熟悉 碳水化合物和聚合物合成，微阵列制造以及表面和柔软的多种方法 纳米材料的特征。此外，我还帮助建立并在 分子铸造厂，当我开始自己的研究实验室时，将获得未来的宝贵体验。 研究：附带的研究建议概述了蛋白聚糖的纳米级代理的设计 （我称其为“ neopgs”）及其用作组织工程支架中的细胞功能调节剂 早期癌症检测的成像剂，以及作为纳米晶生长和的新型大分子模板 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；但是，利用 迄今为止，他们出于医疗目的的独特能力被证明是具有挑战性的。它们的结构复杂性， 组成和功能异质性，非模板生物合成限制了其适用性 生物医学研究。我的建议概述了一种简单的合成策略，该策略翻译了基本的建筑 负责将蛋白聚糖的生物学功能纳入纳米级聚合物NEOPGS的特征。利用优势 在微阵列的技术力量以及我在建造它们方面的技能中，我的团队将构建一个“ Neopg” 芯片”，以迅速询问NEOPG结构的库，以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：该奖项的K99培训部分在我向独立的过渡期间至关重要 我学术生涯的阶段。我打算追求的研究的生物医学重点是我 精通分子和细胞生物学的主题和技术。拟议的培训 Bertozzi教授的指导将帮助我获得这些技能。我将获得的纳米影像技术 通过与Molecular Foundry的James de Yoreo博士的合作，我的研究团队能够 与生物构建块的尺寸相匹配并探索新方法的设计材料 生物界面。可通过 LBNL和UC Berkeley以及我的出色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项宝贵的资产，而我寻求教职员工 美国以及我启动自己的独立职业。 环境：作为Bertozzi实验室的成员，我将可以访问 分子铸造厂以及加州大学伯克利分校化学学院的资源和仪器。这 Bertozzi研究团队的科学卓越和多样性，其良好的高影响力记录 对化学和分子生物学领域的贡献，以及高度协作的氛围教授。 她小组中的Bertozzi养育者将促进我在分子和细胞生物学培训方面的快速进步。 与分子铸造厂与詹姆斯·迪约洛（James Deyoreo）的合作以及铸造厂科学的专业知识 当我接受纳米材料成像培训时，员工将提供重要的支持 表征。最后，加州大学伯克利分校著名的学术和科学界提供了充满活力的 在其中交流思想，建立合作和探索科学领域的新边界的环境，并将 无疑为我的职业发展做出了贡献。