Epigenetic regulatory mechanisms during neurodevelopment

神经发育过程中的表观遗传调控机制

• 批准号: RGPIN-2016-05531
• 负责人: Singh, Shiva
• 金额: $ 3.21万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=628947
• 关键词: Epigenetic; regulatory; mechanisms; during; neurodevelopment

Among other insights, this NSERC funded research has established that the natural variation associated with gene expression is much more common than DNA polymorphism. From evolutionary perspective, this variation offers among the first defence to environmental stresses particularly during neurodevelopment. Further, we have demonstrated that advances in molecular technologies to appraise this variability reliably now offers effective strategies to investigate this defence during neurodevelopment, which has remained enigmatic. Our strategy is to interrupt neurodevelopment at desired time(s) by stressors (eg. alcohol) and evaluate genome-wide changes using RNA-seq and microarrays. The results have allowed us to conclude that alcohol yields a lifelong “molecular footprint” of its encounter during neurodevelopment. Further, this “footprint” may underlie critical behavioral defects often associated with neurodevelopmental exposure to alcohol. This proposal will specifically focus on molecular studies on hippocampus that directs learning and memory often affected by prenatal alcohol.

在其他见解中，这项由NSERC资助的研究已经确定，与基因表达相关的自然变异比DNA多态性更常见。从进化的角度来看，这种变异提供了对环境压力的第一道防线，特别是在神经发育期间。此外，我们已经证明，分子技术的进步，可靠地评估这种变异性，现在提供了有效的策略，以调查这种防御在神经发育过程中，这一直是个谜。我们的策略是在期望的时间通过压力源（例如，酒精），并使用RNA-seq和微阵列评估全基因组变化。研究结果使我们得出结论，酒精会在神经发育过程中产生终身的“分子足迹”。此外，这种“足迹”可能是关键行为缺陷的基础，这些行为缺陷通常与神经发育暴露于酒精有关。这项提案将特别关注海马体的分子研究，海马体指导学习和记忆，经常受到产前酒精的影响。