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中文摘要
翻译
描述(由申请人提供):在本申请中,哈佛大学的一组研究人员寻求资金购买超高分辨率计算机断层扫描系统,用于对转基因小鼠的发育、生长和老化的骨骼、关节、牙齿、眼睛和血管进行三维结构分析。目标是鼓励资助关于骨骼遗传性疾病、骨质疏松症、骨关节炎、炎性骨质流失、退行性眼病和血管异常的疾病机制的研究项目,并加快骨修复和牙齿再生研究的进展。现有的和新的疾病小鼠模型将用于确定疾病进展中的关键机制步骤,确定新的治疗靶点和修复/再生策略。正在研究的小鼠中的许多遗传改变与导致人类遗传性疾病的基因突变相同,而其他人则影响人类疾病中改变的过程。因此,这项研究产生的数据与理解人类疾病的机制高度相关。拟议中的高分辨率Xradia MicroXCT-200扫描仪目前在哈佛医学院/哈佛牙科医学院不可用,将使研究人员能够解决关键问题并收集超出当前成像技术限制的数据。该仪器集成了多项创新技术功能,使其能够超越目前市场上用于生物样品显微断层扫描的所有其他三维X射线显微镜。通过专有的PhaseEnhanced探测器,MicroXCT可以对矿化组织和软组织进行高分辨率(亚微米)三维组织学检查。通过将电子显微镜的对比度增强技术与高分辨率microCT相结合,研究人员相信即使在X射线成像不可能的情况下也可以获得数据。该仪器的收购将加速对人类疾病小鼠模型中疾病相关过程的杰出研究。 公共卫生相关性:该项目提议使用一种新的高分辨率计算机断层扫描仪Xradia MicroXCT-200,在人类疾病小鼠模型中获得正常和患病骨骼、软骨、眼组织和血管的三维图像。该仪器具有超越现有microCT扫描仪的功能,将使研究人员能够收集有关矿化和软组织中致病过程的进展和后果的新数据。这项新技术将加速一些现有研究项目的进展,并产生与重大疾病有关的新见解,如骨骼和关节遗传性疾病、骨质疏松症、关节炎、血管异常、黄斑变性、牙周病和肿瘤。
英文摘要
DESCRIPTION (provided by applicant): In this application, a group of Harvard University investigators seeks funding to purchase an ultra high resolution computed tomography system for 3-dimensional structural analyses of developing, growing and aging bones, joints, teeth, eyes and blood vessels of genetically modified mice. The goal is to stimulate funded research projects on disease mechanisms of inherited disorders of the skeleton, osteoporosis, osteoarthritis, inflammatory bone loss, degenerative eye diseases and vascular anomalies and accelerate progress in studies of bone repair and tooth regeneration. Existing and new mouse models of disease will be used to identify critical mechanistic steps in disease progression, identify novel targets for therapy and strategies for repair/regeneration. Many of the genetic alterations in the mice being studied are identical to gene mutations responsible for inherited disorders in humans, while others are affecting processes that are altered in human disease. The data resulting from this research are therefore highly relevant to understanding mechanisms of human disease. The proposed high resolution Xradia MicroXCT-200 scanner, currently unavailable at Harvard Medical School/Harvard School of Dental Medicine, will enable investigators to address critical questions and collect data that are beyond the limits of current imaging technology. The instrument incorporates several innovative technical features that enable it to outperform all other 3-dimensional X-ray microscopes currently on the market for micro-tomography of biological samples. With proprietary PhaseEnhanced detectors, the MicroXCT makes high resolution (submicron) 3-dimensional histology of both mineralized and soft tissues possible. By combining innovative use of contrast-enhancing techniques of electron microscopy with ultrahigh resolution microCT the investigators believe data can be acquired even in cases where X-ray imaging is otherwise impossible. The acquisition of the instrument will accelerate outstanding research into disease- associated processes in mouse models of human diseases. PUBLIC HEALTH RELEVANCE: This project proposes the use of a new high resolution computed tomography instrument, Xradia MicroXCT-200, to obtain three-dimensional images of normal and diseased bones, cartilage, eye tissues and blood vessels in mouse models of human diseases. The instrument has capabilities that go beyond those of existing microCT scanners and will enable investigators to collect novel data on the progression and consequences of disease-causing processes in both mineralized and soft tissues. This new technology will accelerate progress in a number of existing research projects and generate new insights related to major diseases, such as genetic disorders of bones and joints, osteoporosis, arthritis, vascular anomalies, macular degeneration, periodontal disease and tumors.
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A mechanism for tyrosine phosphorylation of extracellular matrix proteins
  • 批准号:
    9525550
  • 项目类别:
  • 资助金额:
    $22.37万
  • 财政年份:
    2018
  • 负责人:
    BJORN REINO OLSEN
  • 依托单位:
2011 Bones & Teeth Gordon Research Conference
  • 批准号:
    8119252
  • 项目类别:
  • 资助金额:
    $2.7万
  • 财政年份:
    2011
  • 负责人:
    BJORN REINO OLSEN
  • 依托单位:
2009 Gordon Research Conference on Cartilage Biology and Pathology
  • 批准号:
    7672681
  • 项目类别:
  • 资助金额:
    $1.5万
  • 财政年份:
    2009
  • 负责人:
    BJORN REINO OLSEN
  • 依托单位:
Administrative Core
  • 批准号:
    7499200
  • 项目类别:
  • 资助金额:
    $5.6万
  • 财政年份:
    2007
  • 负责人:
    BJORN REINO OLSEN
  • 依托单位:
海外基金