Molecular and Bioinformatic support for the European Xenopus Resource Centre

对生命的基本过程以及这些过程如何出错（例如在疾病或发育过程中）的理解，几乎完全依赖于使用“模型”动物进行的研究，这些“模型”动物已经得到了特别好的理解，并且在实验上易于处理。可以说，这些模式动物中用途最广的是爪蟾的胚胎。为了最有效和高效地利用这些模型，转基因动物本身和用于与它们一起工作的特殊分子工具（通常是DNA和抗体）在研究界内共享。为了做到这一点，每个生物都有资源中心。非洲爪蟾研究中心是欧洲非洲爪蟾资源中心（EXRC），这个应用程序是为了支持那里保存的独特的分子工具集合。该中心的工作人员从世界各地的实验室获得分子工具，培养更多的分子工具，并检查它们是否按预期工作。然后将工具的细节输入到该模型生物的数据库中，该数据库称为Xenbase。它具有复杂的搜索和链接功能，使研究人员可以很容易地找到工具。当用户需要这些工具时，这些工具就会从EXRC发送给支付生产成本的用户。我们的目标是，利用这里申请的资金，首先继续提供当前的分子工具，这些工具的管理最初是由BBSRC支持的。这些工具使研究人员能够确定胚胎中基因的转换位置，制造转基因青蛙并测试基因的功能。我们也在申请资金，为社区开发两个新工具。生物学家需要抗体来“看到”细胞和胚胎中的蛋白质；几年来，爪蟾界已经意识到缺乏用于爪蟾研究的抗体。自20世纪80年代中期以来，EXRC所在的学校一直在成功地培养抗体，并且这样做的规模允许它进行商业供应；我们建议将这种抗体提升管道提供给爪蟾实验室，并支持他们对所产生的抗血清进行初步表征。另一个新工具是物理青蛙的基因组（所有青蛙的DNA），它被称为BACS的非常大的片段。我们将选择跨越整个基因组的BACS，并将其提供给社区。BACS让研究人员改进了青蛙的基因组序列，挽救了突变，并确定了控制特定基因的DNA区域。由于与BACS合作是一项高度专业化的技能，我们聘请了一位专业的BAC科学家来兼职开发这个项目。这一套分子工具，加上EXRC和美国国家爪蟾资源中心（NXR）的转基因、突变和野生型系，以及NXR提供的培训计划，为爪蟾科学家提供了一个优秀的资源基础设施，提高了他们研究计划的效率和有效性。

The understanding of the basic processes of life and how these can go wrong, for example in disease or duringdevelopment, is almost completely dependent on studies using "model" animals that are particularly well understood andexperimentally tractable. Arguably the most versatile of these model animals are the embryos of Xenopus frogs. In order tomake the most effective and efficient use of these models, the genetically altered animals themselves and the specialmolecular tools (generally DNA and antibodies) that are used to work with them are shared within the research community.To do this, resource centres exist for each organism. The centre for Xenopus is the European Xenopus Resource Centre(EXRC), and this application is to support the unique collection of molecular tools held there. Staff at the centre acquire themolecular tools from laboratories around the world, grow more of them them and check that they work as expected. Thedetails of the tools are then entered on the database for this model organism, which is called Xenbase. It has sophisticatedsearching and linking functions so that researchers can find the tools easily. When they are requested, the tools are sentfrom the EXRC to the user who pays for the cost of their production.Our aim, using the funding requested here, is first to continue providing the current molecular tools, the curation of whichwas originally supported by the BBSRC. These tools allow researchers to determine where in embryos genes are switchedon, to make transgenic frogs and to test the function of genes. We are also requesting funding to develop two new tools forthe community. Antibodies are needed by biologists to "see" proteins in cells and embryos; for some years now theXenopus community has been aware of a lack of antibodies for Xenopus research. The School where the EXRC is situatedhas been raising antibodies successfully since the mid-1980s and does so at a scale that allows it to supply commercially;we propose to make this antibody raising pipeline available to Xenopus labs and support them with preliminarycharacterisation of the antiserum produced. The other new tool is the physical frog genome (all of the frog DNA) in verylarge fragments called BACS. We will pick BACS that span the whole genome and make these available to the community.BACS let researchers improve the genome sequence of frogs, rescue mutations and identify the regions of DNA thatcontrol specific genes. Since working with BACS is a highly specialised skill, we have recruited an expert BAC scientist todevelop this project part time.This set of molecular tools, when added to the transgenic, mutant and wild-type lines held at the EXRC and the USNational Xenopus Resource (NXR), together with the training programmes provided at the NXR, give Xenopus scientistsan excellent resource infrastructure that enhances the efficiency and effectiveness of their research programmes.