14CONFAP Understanding diverged genome repair and replication functions in trypanosomatid parasites

14CONFAP 了解锥虫寄生虫中不同的基因组修复和复制功能

• 批准号: BB/M028909/1
• 负责人: Richard McCulloch
• 金额: $ 5.1万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM028909%2F1
• 关键词: 14CONFAP; Understanding; diverged; genome; repair

This proposal has two overarching aims. The first aim is research-driven: we wish to understand the unusual behaviour of a a genome repair pathway termed nucleotide excision repair in two important human pathogens, Trypanosoma brucei (an African trypanosome, which is also an important animal pathogen) and Trypanosoma cruzi (a major parasite in South and Central America). Our rationale for this research is based on previous studies in T. brucei, which have suggested that the nucleotide excision repair machinery that acts to protect the parasite's genome from various forms of damage may have a different composition from what has been described in other organisms, including humans, and that some of the predicted machinery may in fact provide a different (and at the moment unknown) function in the cell. Currently, it is easier and quicker to do genetic experiments in T. brucei than in T. cruzi, and we will pioneer the nucleotide excision repair studies in the former and extend this work to the American trypanosome. In the second aim, we wish to run a residential meeting in Brazil on parasite genome repair and replication, with the purpose of fostering greater long-term links between Brazil and UK researchers in this area.

这项提议有两个最重要的目标。第一个目标是研究驱动的：我们希望了解一种名为核苷酸切除修复的基因组修复途径在两种重要的人类病原体--布氏锥虫(一种非洲锥虫，也是一种重要的动物病原体)和克氏锥虫(南美洲和中美洲的一种主要寄生虫)中的不寻常行为。我们进行这项研究的理由是基于之前对布鲁氏毛滴虫的研究，这些研究表明，保护寄生虫基因组免受各种形式损害的核苷酸切除修复机制可能与在包括人类在内的其他生物中描述的组成不同，而且一些预测的机制实际上可能在细胞中提供不同的(目前未知的)功能。目前，在布氏锥虫中进行基因实验比在克氏锥虫中更容易、更快，我们将开创前者的核苷酸切除修复研究，并将这项工作推广到美国锥虫。在第二个目标中，我们希望在巴西举办一次关于寄生虫基因组修复和复制的常驻会议，目的是促进巴西和英国研究人员在这一领域建立更多的长期联系。

项目成果

The ATR kinase of Trypanosoma brucei links DNA damage signalling and monoallelic control of surface antigen gene expression during antigenic variation

• DOI: 10.1101/435198
• 发表时间: 2018-10
• 期刊: bioRxiv
• 作者: J. Black;K. Crouch;L. Lemgruber;C. Lapsley;N. Dickens;J. Mottram;R. McCulloch

Trypanosoma brucei ATR Links DNA Damage Signaling during Antigenic Variation with Regulation of RNA Polymerase I-Transcribed Surface Antigens

• DOI: 10.1016/j.celrep.2019.12.049
• 发表时间: 2020-01-21
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Black, Jennifer Ann;Crouch, Kathryn;McCulloch, Richard
• 通讯作者: McCulloch, Richard

Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome

• DOI: 10.1101/357020
• 发表时间: 2018-06
• 期刊: Nucleic Acids Research
• 影响因子: 14.9
• 作者: E. Briggs;G. Hamilton;K. Crouch;C. Lapsley;R. McCulloch

Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome.

• DOI: 10.1093/nar/gky928
• 发表时间: 2018-12-14
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Briggs E;Hamilton G;Crouch K;Lapsley C;McCulloch R
• 通讯作者: McCulloch R

Chromosomal copy number variation analysis by next generation sequencing confirms ploidy stability in Trypanosoma brucei subspecies.

• DOI: 10.1099/mgen.0.000223
• 发表时间: 2018-10
• 期刊: Microbial genomics
• 影响因子: 3.9
• 作者: Almeida LV;Coqueiro-Dos-Santos A;Rodriguez-Luiz GF;McCulloch R;Bartholomeu DC;Reis-Cunha JL
• 通讯作者: Reis-Cunha JL