Molecular Analysis of Developmental Brain Disorders Associated with Synaptic Pathology

摘要 突触病的分子机制出现在大量赋予风险的基因的下游， 这些疾病的病因尚不清楚。特别是，不同的风险基因如何分离成共同的 分子机制的识别一直是一个挑战。同样，基因错义变异如何导致 病理学仍然是个谜。这些知识上的差距对该领域构成了重大障碍，并限制了我们的研究。 能够设想改善发病机制的策略。在这个项目中，我们将开发和利用创新的 蛋白质组学，scRNA-seq和基因组工程方法，以解决这些问题，在更大的规模比 以前在动物身上是可能的。我们预计这些数据将提供一个新的和无与伦比的分子 ASD和相关疾病的框架以及未来关于新靶点的研究 行为

ABSTRACT The molecular mechanisms of synaptopathy that arise downstream of the large number of gene conferring risk for these disorders remains unclear. Particularly, how different risk genes may segregate into common molecular mechanisms has been challenging to identify. Likewise, how genetic missense variants result in pathology remains an enigma. These gaps in knowledge pose a significant barrier to the field and limit our ability to envision stratagies to ameliorate pathogenesis. In this project, we will develop and utilize innovative proteomic, scRNA-seq, and genome engineering approaches to solve these problems at larger scales than previously possible in animals. We anticipate these data will provide a new and unparalleled molecular framework for ASD and related disorders as well as future studies on new targets to beneficially modulate behavior.