METAL TRAFFICKING IN MULTICELLULAR SYSTEMS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 痕量金属离子在生物学中起着至关重要的作用。了解痕量金属的无机生理学的一个关键方面是检测元素在组织中的分布。我们已经确定了三个系统，它们将最好地利用XRF成像来深入了解金属稳态。果蝇有能力隔离高水平的铜，从而对后代产生有益的影响。暴露在高铜水平下的父母的后代能够克服与铜稀缺相关的发育延迟。XRF成像将被用来定位这些大量被隔离的铜的存储位置，以及这些铜是否可以遗传给后代。第二个项目涉及斑马鱼中铜的等级。利用基因突变和铜络合剂设计了铜缺乏程度越来越高的斑马鱼胚胎。随着铜水平的下降，非必需的铜依赖过程，如色素沉着，就会消失。然后脊索发育受到影响，最终导致神经变形。已经确定了铜层次结构，其中铜首先针对更基本的系统，然后针对非基本系统。目前尚不清楚这种分级是在系统水平还是细胞水平上实施的，铜是针对负责神经发育的细胞而不是负责色素沉着的细胞，还是铜在所有细胞中的输送是相同的，但细胞内铜的阈值水平需要表达负责色素形成的蛋白质高于表达更重要的蛋白质所需的蛋白质。最终的系统涉及前列腺癌细胞锌分泌的丧失。健康的前列腺体是非常活跃的锌分泌腺。众所周知，前列腺癌细胞表现出锌浓度的大幅下降。XRF成像将用于比较前列腺癌的不同阶段，以确定何时锌掺入减少。

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.