METAL TRAFFICKING IN MULTICELLULAR SYSTEMS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 痕量金属离子在生物学中起着关键作用。了解微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，将最好地利用XRF成像，以了解金属稳态。果蝇具有螯合高水平铜的能力，从而对后代产生有益的影响。接触高水平铜的父母的后代能够克服与铜缺乏相关的发育迟缓。X射线荧光成像将被用来定位大量的铜被储存在哪里，以及这些铜是否可以传递给后代。第二个项目涉及斑马鱼中的铜等级。使用基因突变和铜螯合剂设计了铜缺乏水平增加的斑马鱼胚胎。随着铜水平的降低，非必需的铜依赖过程，如色素沉着，丢失。然后脊索发育受到影响，最后神经变形。已经确定了铜层级，其中铜首先针对更重要的系统，然后针对非重要的系统。目前还不清楚这种层次结构是在系统水平还是细胞水平上实施的，铜是否靶向负责神经发育的细胞而不是负责色素沉着的细胞，或者铜在所有细胞中的递送是否相等，但是阈值细胞铜水平需要表达负责色素沉着的蛋白质，高于表达更必需的蛋白质所需的蛋白质。最后一个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。已知前列腺癌细胞显示锌浓度的大幅降低。XRF成像将用于比较前列腺癌的不同阶段，以确定锌掺入何时减少。

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.