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化学遗传学——一种将科学和分子遗传学的高级教学相结合的通用方法。

Chemical genetics - a versatile method to combine science and higher level teaching in molecular genetics.

机构信息

Department of Biology-Genetics, Philipps-Universität Marburg, Karl-von-Frisch-Str. 8, 35043 Marburg, Germany.

出版信息

Molecules. 2012 Oct 9;17(10):11920-30. doi: 10.3390/molecules171011920.

DOI:10.3390/molecules171011920
PMID:23047488
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6268829/
Abstract

Phosphorylation is a key event in many cellular processes like cell cycle, transformation of environmental signals to transcriptional activation or polar growth. The chemical genetics approach can be used to analyse the effect of highly specific inhibition in vivo and is a promising method to screen for kinase targets. We have used this approach to study the role of the germinal centre kinase Don3 during the cell division in the phytopathogenic fungus Ustilago maydis. Due to the easy determination of the don3 phenotype we have chosen this approach for a genetic course for M.Sc. students and for IMPRS (International Max-Planck research school) students. According to the principle of "problem-based learning" the aim of this two-week course is to transfer knowledge about the broad spectrum of kinases to the students and that the students acquire the ability to design their own analog-sensitive kinase of interest. In addition to these training goals, we benefit from these annual courses the synthesis of basic constructs for genetic modification of several kinases in our model system U. maydis.

摘要

磷酸化是许多细胞过程中的关键事件,如细胞周期、环境信号向转录激活或极性生长的转化。化学遗传学方法可用于分析体内高度特异性抑制的效果,是筛选激酶靶标的有前途的方法。我们使用这种方法研究了生殖中心激酶 Don3 在植物病原真菌 Ustilago maydis 细胞分裂过程中的作用。由于 don3 表型易于确定,我们选择了这种方法为 M.Sc. 学生和 IMPRS(国际马克斯普朗克研究学院)学生开设了一门遗传学课程。根据“基于问题的学习”原则,这门为期两周的课程的目的是将广泛的激酶知识传授给学生,并使学生获得设计自己感兴趣的模拟敏感激酶的能力。除了这些培训目标外,我们还从这些年度课程中受益于我们的模型系统 U. maydis 中几种激酶的遗传修饰的基本构建体的合成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa87/6268829/0ab645f0920a/molecules-17-11920-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa87/6268829/c1a1895bd4c5/molecules-17-11920-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa87/6268829/c9820f84cf7d/molecules-17-11920-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa87/6268829/0ab645f0920a/molecules-17-11920-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa87/6268829/c1a1895bd4c5/molecules-17-11920-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa87/6268829/c9820f84cf7d/molecules-17-11920-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa87/6268829/0ab645f0920a/molecules-17-11920-g003.jpg

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本文引用的文献

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The distinct interaction between cell cycle regulation and the widely conserved morphogenesis-related (MOR) pathway in the fungus Ustilago maydis determines morphology.细胞周期调控与真菌 Ustilago maydis 中广泛保守的形态发生相关(MOR)途径之间的独特相互作用决定了形态。
J Cell Sci. 2012 Oct 1;125(Pt 19):4597-608. doi: 10.1242/jcs.107862. Epub 2012 Jul 5.
2
Cla4 kinase triggers destruction of the Rac1-GEF Cdc24 during polarized growth in Ustilago maydis.Cla4 激酶在构巢曲霉的极性生长过程中触发 Rac1-GEF Cdc24 的降解。
Mol Biol Cell. 2011 Sep;22(17):3253-62. doi: 10.1091/mbc.E11-04-0314. Epub 2011 Jul 14.
3
Septation of infectious hyphae is critical for appressoria formation and virulence in the smut fungus Ustilago maydis.
感染性菌丝的分隔对于黑麦乌米菌(Ustilago maydis)附着胞的形成和毒性至关重要。
PLoS Pathog. 2011 May;7(5):e1002044. doi: 10.1371/journal.ppat.1002044. Epub 2011 May 19.
4
The germinal centre kinase Don3 triggers the dynamic rearrangement of higher-order septin structures during cytokinesis in Ustilago maydis.生发中心激酶Don3在玉米黑粉菌胞质分裂过程中触发高阶Septin结构的动态重排。
Mol Microbiol. 2009 Dec;74(6):1484-96. doi: 10.1111/j.1365-2958.2009.06948.x. Epub 2009 Nov 10.
5
Cdc42 and the Ste20-like kinase Don3 act independently in triggering cytokinesis in Ustilago maydis.Cdc42和类Ste20激酶Don3在玉米黑粉菌中触发胞质分裂时独立发挥作用。
J Cell Sci. 2008 Jan 15;121(Pt 2):143-8. doi: 10.1242/jcs.014449. Epub 2007 Dec 18.
6
Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis.来自活体营养型真菌植物病原体玉米黑粉菌基因组的见解。
Nature. 2006 Nov 2;444(7115):97-101. doi: 10.1038/nature05248.
7
A second-site suppressor strategy for chemical genetic analysis of diverse protein kinases.一种用于多种蛋白激酶化学遗传学分析的第二位点抑制策略。
Nat Methods. 2005 Jun;2(6):435-41. doi: 10.1038/nmeth764.
8
The PAK family kinase Cla4 is required for budding and morphogenesis in Ustilago maydis.PAK家族激酶Cla4是玉米黑粉菌出芽和形态发生所必需的。
Mol Microbiol. 2004 Oct;54(2):396-406. doi: 10.1111/j.1365-2958.2004.04296.x.
9
A reverse genetic approach for generating gene replacement mutants in Ustilago maydis.一种在玉米黑粉菌中产生基因替换突变体的反向遗传学方法。
Mol Genet Genomics. 2004 Sep;272(2):216-26. doi: 10.1007/s00438-004-1047-z. Epub 2004 Aug 17.
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Regulation of cell separation in the dimorphic fungus Ustilago maydis.双型真菌玉米黑粉菌中细胞分离的调控
Mol Microbiol. 2002 Jul;45(1):219-31. doi: 10.1046/j.1365-2958.2002.03010.x.