A global genetic analysis of nematode spliced leader trans-splicing.

线虫剪接前导反式剪接的全局遗传分析。

• 批准号: BB/J007137/1
• 负责人: Jonathan Pettitt
• 金额: $ 44.63万
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ007137%2F1
• 关键词: global; genetic; analysis; nematode; spliced

Nematode worms are one of the most successful groups of animals in terms of absolute biomass and the occupation of a diverse range of habitats. The majority of nematodes are free-living, feeding on microorganisms, but a significant number are parasites of animals or plants. Nematode parasites of humans make a substantial contribution to the global burden of disease, with a handful of nematode species annually accounting for some 46 million disability adjusted life years (DALYs), and plant parasites are responsible for global crop losses estimated at $100 billion each year. Although there are some effective treatments for these parasites, increases in the number and distribution of strains that are resistant to these drugs mean that there is a need to develop new therapeutic treatments. Ideal targets for the development of new therapeutics would be molecules and processes that are found only in nematodes, but are absent from the animals and plants that they infect. Ideally the therapeutic target would be one that is found in all nematodes enabling the development of a drug active against a broad range of nematode infections. One such process is spliced leader trans-splicing, which is an essential part of the way that genes are expressed in nematodes. While we have a good understanding of the main events in this process there have been no systematic investigations into the molecules that are involved. We have identified a new experimental approach to investigate this process in the major experimental system used to study nematode biology, C. elegans. Using this system, we have shown for the first time that is possible to visualise, through changes in the expression of a fluorescent protein, alterations in spliced leader trans-splicing in living animals. We will use this breakthrough to better understand sliced leader trans-splicing, and thereby improve the knowledge upon which the development of new anthelmintic drugs depends.

就绝对生物量和占据各种生境而言，蠕虫是最成功的动物群体之一。大多数线虫是自由生活的，以微生物为食，但也有相当数量的线虫是动物或植物的寄生虫。人类的线虫寄生虫对全球疾病负担做出了重大贡献，少数线虫物种每年约占4600万残疾调整生命年（DIFE），植物寄生虫每年造成全球作物损失估计达1000亿美元。虽然对这些寄生虫有一些有效的治疗方法，但对这些药物具有耐药性的菌株数量和分布的增加意味着需要开发新的治疗方法。开发新疗法的理想目标是只在线虫中发现的分子和过程，但在它们感染的动物和植物中却不存在。理想地，治疗靶标将是在所有线虫中发现的靶标，从而能够开发针对广泛线虫感染的药物活性。一个这样的过程是剪接前导反式剪接，这是线虫中基因表达方式的重要组成部分。虽然我们对这一过程中的主要事件有很好的了解，但还没有对所涉及的分子进行系统的研究。我们已经确定了一种新的实验方法来研究这一过程中的主要实验系统用于研究线虫生物学，C。优美的使用这个系统，我们已经表明，第一次是可能的可视化，通过荧光蛋白的表达变化，在活的动物剪接的领导人反式剪接的改变。我们将利用这一突破来更好地了解切割前导反式剪接，从而提高新的驱虫药物开发所依赖的知识。

项目成果

Resolution of polycistronic RNA by SL2 trans-splicing is a widely conserved nematode trait.

• DOI: 10.1261/rna.076414.120
• 发表时间: 2020-12
• 期刊: RNA (New York, N.Y.)
• 作者: Wenzel M;Johnston C;Müller B;Pettitt J;Connolly B
• 通讯作者: Connolly B

SLIDR and SLOPPR: flexible identification of spliced leader trans-splicing and prediction of eukaryotic operons from RNA-Seq data.

• DOI: 10.1186/s12859-021-04009-7
• 发表时间: 2021-03-22
• 期刊: BMC bioinformatics
• 影响因子: 3
• 作者: Wenzel MA;Müller B;Pettitt J
• 通讯作者: Pettitt J

Deep evolutionary origin of nematode SL2 trans-splicing revealed by genome-wide analysis of the Trichinella spiralis transcriptome

• DOI: 10.1101/642082
• 发表时间: 2019-05
• 期刊: bioRxiv
• 作者: Marius A. Wenzel;Christopher Johnston;B. Müller;J. Pettitt;B. Connolly

Operons are a conserved feature of nematode genomes.

• DOI: 10.1534/genetics.114.162875
• 发表时间: 2014-08
• 期刊: Genetics
• 影响因子: 3.3
• 作者: Pettitt J;Philippe L;Sarkar D;Johnston C;Gothe HJ;Massie D;Connolly B;Müller B
• 通讯作者: Müller B

A high-throughput screen for the identification of compounds that inhibit nematode gene expression by targeting spliced leader trans-splicing.

一种高通量筛选，用于鉴定通过靶向剪接前导反式剪接抑制线虫基因表达的化合物。

• DOI: 10.1016/j.ijpddr.2019.04.001
• 发表时间: 2019
• 期刊: International journal for parasitology. Drugs and drug resistance
• 作者: Pandarakalam GC