Membrane Anchored-Probes for Sensing Analytes at the Cell Surface

用于感测细胞表面分析物的膜锚定探针

• 批准号: 10673869
• 负责人: Mirna El Khatib
• 金额: $ 14.89万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-02 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10673869
• 关键词: Affect; Amendment; Area; Award; Benign; Bone Marrow; Calibration; Cancer Biology; Cell Culture Techniques; Cell Cycle; Cell Proliferation; Cell Survival; Cell membrane; Cell surface; Cells; Cessation of life; Darkness; Development; Disease Progression; Drops; Elements; Endocytosis; Environment; Environmental Risk Factor; Extracellular Space; Foundations; Goals; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Hydrophobicity; Image; Imaging technology; In Vitro; Label; Laboratories; Learning; Leukemic Cell; Location; Malignant - descriptor; Measurement; Measures; Membrane; Metalloporphyrins; Methods; MicroRNAs; Microscopy; Modification; Molecular; Molecular Probes; Monitor; National Heart, Lung, and Blood Institute; Nutrient; Oxygen; Oxygen Consumption; Phase; Phototoxicity; Play; Porphyrins; Predisposition; Proliferating; Property; Recurrence; Research Personnel; Research Project Grants; Resistance; Role; Signaling Molecule; Solid; Specificity; Tail; Time; Toxic effect; Training; arm; biological research; biomedical imaging; cellular imaging; chemotherapy; design; effective therapy; experimental study; extracellular; hematopoietic stem cell fate; hydrophilicity; imaging probe; improved; in vivo; interest; leukemia; leukemic stem cell; leukemic transformation; membrane synthesis; phosphorescence; pre-clinical research; prevent; quantitative imaging; sensor; serial imaging; skills; stem cell niche; stem cells; synthetic construct; therapy outcome; tool; two-photon

Project Summary. Mirna El Khatib is a synthetic organic chemist, whose goal is to transition into the area of biomedical imaging with applications in cancer biology. An NHLBI K25 award will help her to accomplish this transition and simultaneously will lead to exploration and development of a new class of imaging probe, namely Membrane-Anchored Probes (MAP) for oxygen. Longitudinal imaging is an indispensible tool for learning about progression of disease and outcomes of therapies. The first step in this proposal is to develop a general approach to membrane-tethered molecular sensors. Membrane-anchored probes (MAP) offer a unique opportunity to longitudinally image concentrations of nutrients and signaling molecules, in this case oxygen, in the immediate environment of the cell. When used in vivo such probes will remain longer in the region of interest, compared to sensors dissolved in the extracellular milieu. The new MAP for oxygen will be applied towards longitudinal oxygen measurements in the niche of transplanted hematopoietic stem cells (HSCs) and leukemic cells (LCs). This will unravel why HSCs choose to localize in specific regions of the bone marrow (BM) and why leukemic stem cells (LSCs) evade death during chemotherapy.

项目摘要。MiRNA El Khatib是一名合成有机化学家，他的目标是过渡到 生物医学成像及其在癌症生物学中的应用。NHLBI K25奖将帮助她实现这一目标 过渡并同时将导致探索和发展一类新的成像探头，即 用于氧气的膜锚定探针(MAP)。 纵向成像是了解疾病进展和预后的不可或缺的工具 治疗。这项提议的第一步是开发一种膜系留分子的一般方法。 传感器。膜锚定探头(MAP)提供了一个纵向成像浓度的独特机会 营养物质和信号分子，在这种情况下是氧气，在细胞的直接环境中。使用时 在体内，与溶解在体内的传感器相比，这样的探针在感兴趣的区域停留的时间更长 胞外环境。 新的氧气地图将用于在利基地区进行纵向氧气测量 移植的造血干细胞(HSC)和白血病细胞(LCS)。这将揭开为什么HSC选择 定位于骨髓(BM)的特定区域以及白血病干细胞(LSCs)在 化疗。