Molecular Analysis of Developmental Brain Disorders Associated with Synaptic Pathology

摘要 大量致病基因下游突触形成的分子机制 这些疾病的原因尚不清楚。尤其是不同的风险基因如何分离成共同的 分子机制的确定一直是个挑战。同样，基因错义变异是如何导致 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 能够预见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和基因组工程方法在更大范围内解决这些问题 以前在动物身上也是可能的。我们预计这些数据将提供一个新的和无与伦比的分子 自闭症和相关疾病的框架以及对有益调节的新靶点的未来研究 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.