That which does not kill us makes us stronger: Differential sensitivity to metal exposure during zebrafish embryogenesis and the impact of pre-exposur

杀不死我们的会让我们更强大：斑马鱼胚胎发生过程中对金属暴露的不同敏感性以及预暴露的影响

基本信息

批准号：
1920894
负责人：
金额：
--
依托单位：
UNIVERSITY OF EXETER
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1920894
关键词：
does kill us makes stronger

项目摘要

This studentship aims to document the epigenetic regulation of sexual differentiation and development in a fish model and how this process is perturbed by exposure to environmental stressors. The project will address the hypothesis that the (epi)genomic environment of the developing germ cells within the gonads plays a key role on the process of sex determination and subsequent differentiation of those germ cells. We also hypothesise that that some environmental stressors will perturb these processes, potentially leading to adverse outcomes for reproduction, which may be inheritable via epigenetic mechanisms in some cases. The work will focus on two ubiquitous stressors affecting fish populations worldwide, hypoxia and bisphenol A. Hypoxia is one of the most important global threats to freshwater and marine ecosystems worldwide, resulting in mass mortalities. When oxygen depletion is mild, disruption of sex differentiation in fish can to occur with potential population level consequences in affected ecosystems. Bisphenol A, a component of plastics, is present in aquatic systems globally and has been detected in over 90% of people tested. Exposure to bisphenol A causes disruption of reproduction, changes in epigenetic markers and is associated with a wide range of diseases including cardiovascular disease. These stressors are of great concern globally and there is a need to understand how they cause their effects and whether exposures can result in long term adverse effects later in life or in subsequent generations.To do this, the student will first investigate the epigenomic regulation of sexual differentiation and development in the germ cells using the zebrafish as a model. This will be achieved by isolating germ cells during the developmental windows where major sex differentiation events occur, and quantifying the transcriptome, methylome and miRNAs on those isolated cells. The student will then test how exposures to hypoxia and bisphenol A affect the development of the germ cells. Finally, the student will investigate whether the adverse effects of these stressors can be inherited via epigenetic mechanisms to subsequent generations, by conducting multigenerational studies.The research outcomes of the proposed work will provide the first global characterisation of the epigenomic factors regulating sex differentiation and development in germ cells, and the effects of globally important stressors on those processes. Given the importance of reproduction for the sustainability of fish populations, this knowledge is highly relevant to support appropriate management and regulatory decisions, and to better protect the aquatic environment.The collaboration between Cefas and the University of Exeter will bring together expertise in fish reproductive biology, epigenetics and bioinformatics that will strongly benefit all partners involved. The student will benefit from outstanding training, support and facilities on both academic and governmental research environments, covering both subject specific training and generic training in transferable skills, and will be nurtured to develop as an independent scientist able to contribute to the international research community.

该奖学金旨在记录鱼类模型中性别分化和发育的表观遗传调控，以及这一过程如何因暴露于环境压力而受到干扰。该项目将提出这样一个假设：性腺内发育中的生殖细胞的（表观）基因组环境在这些生殖细胞的性别决定和随后的分化过程中起着关键作用。我们还假设，一些环境压力因素会扰乱这些过程，可能导致生殖不良结果，在某些情况下，这可能通过表观遗传机制遗传。这项工作将重点关注影响全球鱼类种群的两种普遍存在的压力源：缺氧和双酚 A。缺氧是对全世界淡水和海洋生态系统最重要的全球威胁之一，导致大量死亡。当氧气消耗轻微时，鱼类的性别分化可能会受到破坏，从而在受影响的生态系统中产生潜在的种群水平后果。双酚 A 是塑料的一种成分，全球水生系统中都存在双酚 A，超过 90% 的受检者均检测到双酚 A。接触双酚 A 会导致生殖破坏、表观遗传标记发生变化，并与包括心血管疾病在内的多种疾病相关。这些压力源在全球范围内受到高度关注，有必要了解它们如何产生影响，以及接触这些压力源是否会对以后的生活或后代造成长期不利影响。为此，学生将首先研究这些压力源的表观基因组调控。以斑马鱼为模型，研究生殖细胞的性分化和发育。这将通过在发生主要性别分化事件的发育窗口期间分离生殖细胞，并对这些分离细胞上的转录组、甲基化组和 miRNA 进行定量来实现。然后，学生将测试暴露于缺氧和双酚 A 如何影响生殖细胞的发育。最后，学生将通过进行多代研究来调查这些压力源的不利影响是否可以通过表观遗传机制遗传给后代。拟议工作的研究成果将提供调节性别分化和发育的表观基因组因素的第一个全球特征生殖细胞中，以及全球重要的压力源对这些过程的影响。鉴于繁殖对鱼类种群可持续性的重要性，这些知识对于支持适当的管理和监管决策以及更好地保护水生环境高度相关。Cefas 和埃克塞特大学之间的合作将汇集鱼类繁殖生物学方面的专业知识、表观遗传学和生物信息学将使所有相关合作伙伴受益匪浅。学生将受益于学术和政府研究环境中的出色培训、支持和设施，涵盖学科特定培训和可转移技能的通用培训，并将被培养成为一名能够为国际研究界做出贡献的独立科学家。