Understanding the interaction of Memo1 and Runx2 in craniodental mineralization

了解 Memo1 和 Runx2 在颅齿矿化中的相互作用

基本信息

批准号：
10019128
负责人：
Eric Van Otterloo
金额：
$ 24.9万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10019128
关键词：
Advisory Committees Affect Ameloblasts Amelogenesis Area Automobile Driving Binding Bioinformatics Biology Blood Vessels CBFB gene Career Mobility Cartilage Cell Culture Techniques Cell Line Cell Lineage Cells Cephalic ChIP-seq Colorado Complement Complex Core Facility DNA Binding Data Set Defect Dental Dental Enamel Development Development Plans ERBB2 gene Ectoderm Embryo Embryonic Development Ensure Enterobacteria phage P1 Cre recombinase Environment Face Faculty Feedback Funding Gene Expression Generations Genes Genetic Genetic Diseases Goals Head Health Human In Vitro Knowledge Lead Mediator of activation protein Mentors Mesoderm Minerals Modeling Molecular Neural Crest Cell Oral Osteoblasts Osteogenesis Pathology Patients Phenotype Physiologic Ossification Physiologic calcification Play Positioning Attribute Process Protein Isoforms Regulator Genes Reporting Research Research Personnel Research Project Grants Research Proposals Resources Role Skeleton Structure Testing Time Tissues Tooth structure Training Training Programs Universities Work base biomineralization bone career development cell motility craniofacial craniofacial complex craniofacial tissue cranium developmental disease gene function human disease improved in silico in vivo insight member mineralization mutant novel oral ectoderm post-doctoral training prevent promoter research and development skeletal skills skull base stem success symposium tissue regeneration transcription factor transcriptome sequencing

项目摘要

The long-term goals of the applicant are to become a successfully funded, independent, craniofacial developmental biologist, conducting human-disease-focused and translatable research aimed at improving dental, oral, and craniofacial health. This overarching goal will be actualized by the implementation of a highly coordinated, thorough, and integrated career development plan including components of mentored guidance and training, an adept research environment, and a complementary research project. First, a career development plan comprised of a mentor, advisory committee, collaborators, and courses and conferences has been established to provide the applicant with the skills and guidance to transition into a position of independence in a timely manner. The mentor, Dr. Williams, is a successfully funded researcher and leading expert in craniofacial biology and is thus well suited to oversee the applicant’s training. The advisory committee includes both internal and external members that will provide critical guidance and feedback on aspects of career development and technical components of cranial bone, tooth, enamel, cell culture, bioinformatic, and gene-editing biology. The committee also includes two young faculty members who will specifically assist the applicant in components directly related to career transition. In addition, courses in bioinformatics and conferences on bone and tooth development and biomineralization are included to facilitate these components of the training program. Second, an adept research environment – the Department of Craniofacial Biology, the University of Colorado, along with associated resources, core facilities, and faculty members not directly involved in the applicant’s advisory committee – is established to provide assurance of the applicant’s success. Third, a research project has been proposed to facilitate training of the applicant in new areas of biology essential for his path to independence while simultaneously maintaining the key goals of improving dental, oral, and craniofacial health. Central to these goals are understanding the unique gene regulatory networks driving cranial skeletal mineralization – a process that is well described in the mesoderm-derived trunk skeleton yet lacks clarity in the cranial skeleton owing to its unique developmental origins. To this end, the research proposal utilizes three aims to test the important hypothesis that Memo1 and Runx2 genetically integrate to drive mineralization of key craniodental structures, including teeth and bones. Aim I will establish whether Memo1 expression is directly regulated by RUNX2 in the context of in vivo cranial endochondral ossification and in vitro amelogenesis. Aim II will more specifically determine the role of MEMO1 in cranial endochondral ossification and its genetic integration with Runx2-II in this process. Finally, Aim III will establish the role these molecules play in mineralization of the enamel layer during tooth development. Collectively, this comprehensive career development and research plan will ensure the successful transition of the applicant from a dependent research position into one of well-prepared independence.

申请人的长期目标是成为一名成功资助的、独立的、颅面发育生物学家，进行以人类疾病为中心的可转化研究，旨在改善牙齿、口腔和颅面健康这一总体目标将通过实施高度重视的计划来实现。协调、彻底和综合的职业发展计划，包括指导性指导的组成部分和培训、良好的研究环境和互补的研究项目首先是职业。发展计划由导师、咨询委员会、合作者以及课程和会议组成已成立，旨在为申请人提供过渡到职位的技能和指导及时独立，导师威廉姆斯博士是一位成功资助的研究员和领导者。颅面生物学专家，因此非常适合监督申请人的培训。包括内部和外部成员，他们将就各方面提供关键指导和反馈颅骨、牙齿、牙釉质、细胞培养、生物信息学等的职业发展和技术组成部分该委员会还包括两名年轻的教员，他们将专门协助该研究。与职业转型直接相关的申请人此外，生物信息学和课程。包括关于骨骼和牙齿发育以及生物矿化的会议，以促进这些组成部分第二，良好的研究环境——颅面生物学系，科罗拉多大学，以及相关资源、核心设施和非直接的教职人员参与申请人的咨询委员会——成立是为了确保申请人的成功。第三，提出了一个研究项目，以促进申请人在生物学新领域的培训这对于他走向独立之路至关重要，同时保持改善牙科、口腔、这些目标的核心是了解驱动的独特基因调控网络。颅骨骨骼矿化——这一过程在中胚层衍生的躯干骨骼中得到了很好的描述由于其独特的发育起源，颅骨骨骼缺乏清晰度。该提案利用三个目标来检验 Memo1 和 Runx2 基因整合的重要假设促进包括牙齿和骨骼在内的关键颅齿结构的矿化。 Memo1 表达在体内颅骨软骨内骨化过程中受 RUNX2 直接调节 Aim II 将更具体地确定 MEMO1 在颅骨软骨内的作用。最后，Aim III 将确定这些作用。总的来说，分子在牙齿发育过程中参与牙釉质层的矿化。全面的职业发展和研究计划将确保申请人的成功过渡从依赖的研究职位转变为准备充分的独立研究职位。