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

• 批准号: 10063988
• 负责人: Eric Van Otterloo
• 金额: $ 24.6万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 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/10063988
• 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

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个成功资助，独立，颅面 发展生物学家，进行人类疾病为重点和可翻译的研究，旨在改善 牙齿口腔和颅面健康这一总体目标将通过实施一项高度 协调、全面和综合的职业发展计划，包括辅导指导的组成部分 和培训，一个熟练的研究环境，和一个互补的研究项目。第一，职业生涯 发展计划包括导师、咨询委员会、合作者、课程和会议 已经建立，以提供申请人的技能和指导，过渡到一个职位， 及时独立。导师威廉姆斯博士是一位成功资助的研究人员， 他是颅面生物学方面的专家，因此非常适合监督申请人的培训。咨询委员会 包括内部和外部成员，他们将提供关键的指导和反馈， 职业发展和颅骨，牙齿，釉质，细胞培养，生物信息学的技术组成部分， 基因编辑生物学该委员会还包括两名年轻的教师，他们将专门协助 申请人在与职业转型直接相关的组件中。此外，生物信息学课程和 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 的培训计划。第二，一个熟练的研究环境-颅面生物学系， 科罗拉多大学，沿着相关资源，核心设施和教师不直接 参与申请人的咨询委员会-旨在确保申请人成功。 第三，提出了一个研究项目，以促进在生物学新领域培训申请人 这对他走向独立的道路至关重要，同时保持改善牙科，口腔， 和颅面健康这些目标的核心是了解独特的基因调控网络， 颅骨骼矿化-一个在中胚层衍生的躯干骨骼中得到很好描述的过程， 由于其独特的发育起源，头骨骨骼缺乏清晰度。为此，研究 该提案利用三个目标来检验Memo 1和Runx 2基因整合以 驱动关键颅齿结构的矿化，包括牙齿和骨骼。我将确定是否 Memo 1表达在体内颅骨软骨内骨化中受RUNX 2直接调控 和体外成釉。目的II将更具体地确定MEMO 1在颅软骨内分泌中的作用。 骨化及其与Runx 2-II的遗传整合。最后，目标三将确立这些 分子在牙齿发育期间的釉质层矿化中起作用。总的来说，这 全面的职业发展和研究计划将确保申请人的成功过渡 从一个依赖性的研究职位转变为一个准备充分的独立职位。