Molecular and Bioinformatic support for the European Xenopus Resource Centre

对欧洲爪蟾资源中心的分子和生物信息支持

• 批准号: BB/K019988/1
• 负责人: Matt Guille
• 金额: $ 73.5万
• 依托单位: University of Portsmouth
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK019988%2F1
• 关键词: Molecular; Bioinformatic; support; European; Xenopus

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.

对生命的基本过程以及这些过程如何出错的理解，例如在疾病或发育过程中，几乎完全依赖于使用“模型”动物的研究，这些动物特别容易理解和实验上容易处理。可以说，这些模型动物中最通用的是非洲爪蟾蛙的胚胎。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合作的特殊分子工具（通常是DNA和抗体）在研究界内部共享。为此，每种生物都有资源中心。非洲爪蟾的中心是欧洲爪蟾资源中心（EXRC），这个应用程序是为了支持那里独特的分子工具收集。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。然后将工具的详细信息输入该模式生物的数据库，称为Xenbase。它具有扩展的搜索和链接功能，使研究人员可以很容易地找到工具。当需要时，EXRC会将这些工具发送给用户，用户支付其生产成本。我们的目标是，使用这里所要求的资金，首先继续提供目前的分子工具，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启动位置，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“观察”细胞和胚胎中的蛋白质;几年来，爪蟾社区已经意识到爪蟾研究缺乏抗体。EXRC所在的学校自20世纪80年代中期以来一直在成功地提高抗体，并以允许其商业化供应的规模这样做;我们建议将这种抗体提高管道提供给非洲爪蟾实验室，并支持他们对所产生的抗血清进行定性分析。另一个新的工具是青蛙的物理基因组（所有的青蛙DNA）在非常大的片段称为BACS。我们将挑选涵盖整个基因组的BACS，并将其提供给社区。BACS让研究人员改进青蛙的基因组序列，拯救突变，并识别控制特定基因的DNA区域。由于与BACS合作是一项高度专业化的技能，我们聘请了一位专家BAC科学家来兼职开发这个项目。这套分子工具，当添加到EXRC和美国国家爪蟾资源（NXR）的转基因，突变和野生型品系中时，以及NXR提供的培训课程，为非洲爪蟾科学家提供一个优良的资源基础设施，提高他们的研究计划的效率和效果。

项目成果

Adipose tissue macrophages develop from bone marrow-independent progenitors in Xenopus laevis and mouse.

脂肪组织巨噬细胞是由爪诺氏爪蟾和小鼠中骨髓依赖的祖细胞发展而来的。

• DOI: 10.1189/jlb.1a0317-082rr
• 发表时间: 2017-09
• 期刊: Journal of leukocyte biology
• 影响因子: 5.5
• 作者: Hassnain Waqas SF;Noble A;Hoang AC;Ampem G;Popp M;Strauß S;Guille M;Röszer T
• 通讯作者: Röszer T

CRISPR/Cas9 Gene Disruption Studies in F0 Xenopus Tadpoles: Understanding Development and Disease in the Frog.

F0 级爪蟾蝌蚪中的 CRISPR/Cas9 基因破坏研究：了解青蛙的发育和疾病。

• DOI: 10.1007/978-1-0716-3004-4_10
• 发表时间: 2023
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Abu-Daya A

Identification and functional evaluation of GRIA1 missense and truncation variants in individuals with ID: An emerging neurodevelopmental syndrome.

• DOI: 10.1016/j.ajhg.2022.05.009
• 发表时间: 2022-07-07
• 期刊: American journal of human genetics
• 影响因子: 9.8

Biallelic variants in COPB1 cause a novel, severe intellectual disability syndrome with cataracts and variable microcephaly.

• DOI: 10.1186/s13073-021-00850-w
• 发表时间: 2021-02-25
• 期刊: Genome medicine
• 影响因子: 12.3
• 作者: Macken WL;Godwin A;Wheway G;Stals K;Nazlamova L;Ellard S;Alfares A;Aloraini T;AlSubaie L;Alfadhel M;Alajaji S;Wai HA;Self J;Douglas AGL;Kao AP;Guille M;Baralle D
• 通讯作者: Baralle D

Additional file 1 of Biallelic variants in COPB1 cause a novel, severe intellectual disability syndrome with cataracts and variable microcephaly

COPB1 中双等位基因变异的附加文件 1 导致一种新型严重智力障碍综合征，伴有白内障和可变小头畸形

• DOI: 10.6084/m9.figshare.14121908
• 发表时间: 2021
• 作者: Macken W