Epigenetic mechanisms and consequences of fathering in sticklebacks

 描述（由申请人提供）：我们对父亲的理解远远落后于我们对母亲的理解，但父亲对后代的福祉有着重大影响。该应用程序的总体目标是了解行为，分子和 表观遗传机制，有助于父亲对后代的影响。核心假设是，父亲，像母亲一样，对后代的行为具有持久的跨代后果，这些后果是通过影响大脑基因表达的基因组中的表观遗传变化介导的。这项研究的基本原理是，在一个具有复杂父系行为的易驾驭脊椎动物系统中研究社会行为的自然变异，很可能成功地确定其他生物体（包括人类）中父亲行为的原因和后果。具体目标有两个：1：确定父职对后代影响的敏感期和分子机制。这一目标的工作假设是，父亲在发育的敏感时期影响后代的基因表达，并对后代以后的行为产生影响。2：识别由父亲引起的表观遗传修饰。这一目标的工作假设是，父亲对基因组进行表观遗传修饰，影响后代大脑基因表达、行为和压力生理。这个项目的预期成果是详细了解的基本机制，不同的父亲风格所创造的家庭环境对后代施加保护作用。这些结果预计将产生重要的积极影响，因为了解父亲对后代的影响可以加强促进健康行为的干预措施的发展。拟议的研究的贡献，预计将是一个详细的了解行为，分子和表观遗传机制，父亲影响他们的后代使用一个新的模型系统的父亲。这一贡献将是重要的，因为它将揭示父亲是否像母亲一样，可以通过基因组的表观遗传修饰来影响后代。这项研究是创新的，因为它利用了一种新的基因组模式生物，其中父亲是父母照顾的唯一提供者（threespined stickleback fish）。使用像刺鱼这样只有父亲照顾的系统的好处是，我们可以将父亲的影响从母亲的影响中分离出来。

 DESCRIPTION (provided by applicant): Our understanding of fathering has lagged far behind our understanding of mothering, yet fathers have a substantial impact on the well-being of their offspring. The overall objective of this application is to understand the behavioral, molecular and epigenetic mechanisms that contribute to the effects of fathering on offspring. The central hypothesis is that fathering, like mothering, has long-lasting, transgenerational consequences for offspring behavior that are mediated via epigenetic changes in the genome that influence brain gene expression. The rationale that underlies the proposed research is that studying natural variation in social behavior in a tractable vertebrate system with sophisticated paternal behaviors is likely to have success identifying the causes and consequences of fathering in other organisms, including humans. There are two specific aims: 1: Identify the sensitive period and the molecular mechanisms underlying the effect of fathering on offspring. The working hypothesis for this aim is that fathering influences offspring gene expression during a sensitive period in development that has consequences for offspring behavior later in life. 2: Identify the epigenetic modifications caused by fathering. The working hypothesis for this aim is that fathering causes epigenetic modifications to the genome that influence offspring brain gene expression, behavior and stress physiology. The expected outcome of this project is a detailed understanding of the basic mechanisms by which family environments created by different fathering styles exert protective effects on offspring. These outcomes are expected to have an important positive impact because understanding the impacts of fathers on offspring could enhance the development of interventions that promote the adoption of healthy behaviors. The contribution of the proposed research is expected to be a detailed understanding of the behavioral, molecular and epigenetic mechanisms by which fathers influence their offspring using a new model system for fathering. This contribution will be significant because it will reveal if fathering, like mothering, can influence subsequent generations via epigenetic modifications to the genome. The proposed research is innovative because it utilizes a new genomically-enabled model organism in which fathers are the sole providers of parental care (threespined stickleback fish). The benefit of using a system with sole paternal care such as sticklebacks is that we can isolate the effects of fathering from the effects of mothering.