STUDIES OF IRON TRANSPORT AND HOMEOSTASIS; STUDIES OF ARCHAEAL VIRUS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。一方面，全世界有超过10亿人患有贫血（缺铁）。另一方面，遗传性血色素沉着症（铁超载）是最常见的常染色体隐性遗传病，在北方欧洲血统的人群中，其携带者频率约为1/10。此外，已知许多其他铁过载疾病，通常导致50岁之前死亡。我们正在从事一些蛋白质的结构研究，这些蛋白质涉及哺乳动物的铁转运和体内平衡。这些蛋白质中的一些在嗜热生物中具有同源物，因此我们还进行了硫磺硫化叶菌铁转运的结构研究。第二个项目的重点是肠道病毒的结构研究。已知有超过5,000种病毒和噬菌体感染细菌和真核生物，然而，只有不到35种病毒被鉴定出来，主要是因为人们才刚刚开始寻找它们。第一个人类基因组现在已经测序，它们通常与公共数据库缺乏同源性。因此，如果没有直接的生物化学和遗传学研究，很难确定这些病毒基因的功能。在两个案例中，我们已经证明这些病毒蛋白的结构可以提示功能，我们现在正在进行一项小规模的结构蛋白质组学研究，重点是几个泉古菌病毒家族的类型病毒。这将有助于勾勒出生命树中第三个分支的病毒生命周期，也可能识别出在生物技术中具有潜在用途的耐热酶。

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. On one hand, more than 1 BILLION people world-wide suffer from anemia (iron deprivation). On the other, hereditary hemochromatosis (iron overload) is the most prevalent autosomal recessive disease known with a carrier frequency of approximately 1 in 10, in people of northern European extraction. In addition, many other diseases of iron overload are known, often leading to death by age 50. We are engaged in structural studies of a number of proteins involved mammalian iron transport and homeostasis. Some of these proteins have homologues in thermophilic organisms, thus we have also undertaken structural studies of iron transport in Sulfolobus solfataricus. A second project focuses on structural studies of Archaeal viruses. More than 5,000 viruses and phage are known that infect bacteria and the eukaryotes, however, less than 35 Archaeal viruses have been identified, primarily because people are just beginning to look for them. The first Archaeal genomes have now been sequenced, and they generally show a lack of homology with the public databases. Thus it is difficult to assign function to these viral genes without direct biochemical and genetic studies. In two cases, we have demonstrated that the structures of these viral proteins can suggest function, and we are now engaged in a small scale structural proteomics effort focused on the type viruses of several crenarchaeal virus families. This will help to sketch in the viral life cycles for the viruses from this third branch in the tree of life, and may also identify thermostable enzymes with potential uses in biotechnology.