Membrane Anchored-Probes for Sensing Analytes at the Cell Surface

项目摘要。Mirna El Khatib是一位合成有机化学家，其目标是过渡到 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，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。 治疗该建议的第一步是开发一种膜系分子的通用方法， 传感器.膜锚定探针（MAP）提供了一个独特的机会，纵向图像浓度 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，与溶解在生物传感器中的传感器相比， 细胞外环境 新的氧气MAP将用于纵向氧气测量， 移植的造血干细胞（HSC）和白血病细胞（LC）。这将揭示为什么HSC选择 定位于骨髓（BM）的特定区域，以及为什么白血病干细胞（LSC）在 化疗

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.