Mechanisms of Brain-specific Angiogenesis Inhibitor 1 (BAI1) in neural developmen

描述（由申请人提供）本提案为K01指导研究科学家发展奖。该候选人是一名接受过细胞生物学和生物物理学训练的博士后。本提案的目标是将候选人转变为分子和发育神经科学。该候选人正在努力建立一个研究实验室，研究神经元发育机制，重点是信号和信号集成；这些研究将导向对精神疾病的理解和治疗。本文的研究目的是阐明脑血管生成抑制剂I （brain angiogenesis inhibitor I, BAI1）介导树突和树突棘形成的机制。BAI1是异聚g蛋白偶联受体（gpcr） B家族的成员，具有广泛的细胞外片段

DESCRIPTION (provided by applicant) This proposal is for a K01 Mentored Research Scientist Development Award. The candidate is a postdoctoral associate with training in cell biology and biophysics. The goal of this proposal is to transition the candidate into molecular and developmental neuroscience. The candidate is working towards the establishment of a research lab studying the mechanisms of neuronal development with emphasis on signals and signal integration; these studies will be directed toward the understanding and treatment of mental disease. The research goal of this proposal is to elucidate the mechanisms by which brain angiogenesis inhibitor I (BAI1) mediates the formation of dendrites and dendritic spines. BAI1 is member of the B family of heteromeric G-protein coupled receptors (GPCRs) and possesses both an extensive extracellular segment containing thrombospondin repeats and a long cytoplasmic segment containing multiple potential signaling domains flanking the central GPCR moiety. The candidate's preliminary data demonstrate that (1) BAI1 is critical for the proper formation of dendrites and dendritic spines in hippocampal pyramidal neurons, (2) BAI1 interacts with Tiam1, an activator of the small GTPase Rac that links extracellular signals to dendrite and spine growth and development, and (3) BAI1 affects the actin cytoskeleton, at least partially through Rac. A variety of techniques will be used (1) to determine the domain(s) of BAI1 that is (are) required to promote the development of dendrites and dendritic spines, and (2) to measure the effects of BAI1 on dendritic and spine developmental pathways involving Rac. In particular, the candidate will investigate the role of BAI1 in modulating the activation of Rac through Tiam1 in response to brain-derived neurotrophic factor through its receptor TrkB. During this time, the candidate will participate in a variety of neuroscience teaching exercises, both formal and informal. The mentoring team includes both a well-known senior neuroscientist and an exciting young investigator. This training will address the candidate's long term goal of becoming a principal investigator by providing a high-quality environment in which to learn techniques, do research, and generate publications. In addition, the candidate will benefit from career development opportunities provided by Baylor College of Medicine and his senior co-mentor, be exposed to a large variety of scientific opportunities at the Texas Medical Center, observe a laboratory being set up, and receive training in the ethical conduct of research. Both the training and research plans are facilitated by the availability of advanced imaging and other research technologies at Baylor, as well as the highly collaborative and excellent community of world-class researchers present there. PUBLIC HEALTH REVELANCE: Defects in dendrite and dendritic spine formation underlie many forms of mental disease, including autism, depression, and disorders associated with chronic stress. These defects also contribute to the pathologies of mental diseases, neurodegenerative diseases, and traumatic brain injuries. Determination of the signaling mechanisms that direct dendrite and spine formation should unveil new strategies for the treatment of these disorders.