METAL TRAFFICKING IN MULTICELLULAR SYSTEMS

多细胞系统中的金属贩运

• 批准号: 7954529
• 负责人: ANIRUDDHA DEB
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954529
• 关键词: Affect; Biology; Cells; Chelating Agents; Computer Retrieval of Information on Scientific Projects Database; Copper; Detection; Development; Developmental Delay Disorders; Drosophila genus; Embryo; Funding; Future Generations; Gene Mutation; Gland; Grant; Homeostasis; Image; Indium; Institution; Ions; Malignant neoplasm of prostate; Metals; Neurologic; Parents; Physiology; Pigmentation physiologic function; Play; Process; Prostate; Proteins; Research; Research Personnel; Resources; Role; Source; Staging; System; Tissues; Trace metal; United States National Institutes of Health; Zebrafish; Zinc; cancer cell; design; hypocupremia; insight; notochord development; offspring; structural biology; synchrotron radiation; trafficking; Affect; Biology; Cells; Chelating Agents; Computer Retrieval of Information on Scientific Projects Database; Copper; Detection; Development; Developmental Delay Disorders; Drosophila genus; Embryo; Funding; Future Generations; Gene Mutation; Gland; Grant; Homeostasis; Image; Indium; Institution; Ions; Malignant neoplasm of prostate; Metals; Neurologic; Parents; Physiology; Pigmentation physiologic function; Play; Process; Prostate; Proteins; Research; Research Personnel; Resources; Role; Source; Staging; System; Tissues; Trace metal; United States National Institutes of Health; Zebrafish; Zinc; cancer cell; design; hypocupremia; insight; notochord development; offspring; structural biology; synchrotron radiation; trafficking

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Trace metal ions play a critical role in biology. One critical aspect of understanding the inorganic physiology of trace metals is detection of the distribution of the elements in tissues. We have identified three systems that would best exploit XRF imaging to give insight into metal homeostasis. Drosophila has the ability to sequester high levels of copper, resulting in a beneficial effect on the future generations. The offspring of parents that have been exposed to high copper levels are able to overcome developmental delays associated with copper scarcity. XRF imaging would be used to locate where this large amount of sequestered copper is stored and if this copper can be passed on to offspring. The second project deals with the copper hierarchy in Zebrafish. Zebrafish embryos with increasing levels of copper deficiency have been designed using genetic mutation and copper chelators. As copper levels decrease, non-essential copper dependent processes, such as pigmentation, are lost. Then notochord development is affected and finally neurological deformation. A copper hierarchy has been identified where copper is target to more essential systems first and then to non-essential systems. It is unknown whether this hierarchy is enforced on a systemic level or a cellular level, is copper targeted to the cells responsible for neurological development over those responsible for pigmentation, or is copper delivery equal in all cells but the threshold cellular copper levels need to express the proteins responsible for pigmentation higher that those needed for expression of more essential proteins. The final system involves loss of zinc secretion in prostate cancer cells. Healthy prostate glands are extremely active zinc secreting glands. It is known that prostate cancer cells show a large reduction in the concentration of zinc. XRF imaging will be used to compare different stages of prostate cancer to determine when the zinc incorporation is reduced.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 痕量金属离子在生物学中起关键作用。理解痕量金属无机生理的一个关键方面是检测组织中元素的分布。我们已经确定了三个最能利用XRF成像的系统，以深入了解金属稳态。果蝇具有隔离高水平的铜的能力，从而对子孙后代产生有益的影响。暴露于高铜水平的父母的后代能够克服与铜短缺相关的发育延迟。 XRF成像将用于定位大量隔离铜的位置，如果可以将此铜传递到后代。第二个项目涉及斑马鱼的铜层次结构。斑马鱼胚胎具有铜缺乏水平的升高，已使用基因突变和铜螯合剂设计。随着铜水平的降低，诸如色素沉着之类的非必需铜依赖性过程将丢失。然后，脊索发育受到影响，最后神经变形。已经确定了铜层次结构，即铜是首先针对更重要的系统，然后是非必需系统的目标。尚不清楚该层次结构是在全身水平还是细胞水平上执行的，是针对负责色素沉着的细胞的细胞的铜，还是所有细胞中的铜递送相等，但阈值细胞铜水平需要表达蛋白质的蛋白质，使蛋白质表达较高的蛋白质所需的蛋白质，以表达更重要的蛋白质表达的蛋白质。最终系统涉及前列腺癌细胞中锌分泌的丧失。健康的前列腺是非常活跃的锌分泌腺体。众所周知，前列腺癌细胞的锌浓度大大降低。 XRF成像将用于比较前列腺癌的不同阶段，以确定何时减少锌掺入。