Determinants of Neural & Embryonic Stem Cell Potency

神经的决定因素

• 批准号: 7285168
• 负责人: Robert Blelloch
• 金额: $ 17.52万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7285168
• 关键词: Address; Adult; Advisory Committees; Age; Applications Grants; Area; Basic Science; Biological Models; Candidate Disease Gene; Cell Differentiation process; Cell Nucleus; Cells; Cellular biology; Chimera organism; Chromatin; Clinical; Clinical effectiveness; Cloning; Commit; Development; Developmental Biology; Disease; Doctor of Philosophy; ES Cell Line; Embryo; Embryonic Development; Enzymes; Epigenetic Process; Fellowship; Genes; Genetic; Genome; Goals; Head; Hippocampus (Brain); Human; Individual; Lead; Medicine; Mental disorders; Mentors; Mentorship; Methods; Methylation; Modification; Molecular; Molecular Biology; Molecular Profiling; Mus; Nature; Nerve Degeneration; Neuraxis; Neurodegenerative Disorders; Neurons; Newborn Infant; Nuclear; Oocytes; Pathology; Pathway interactions; Physicians; Population; Process; Production; Proteins; Regenerative Medicine; Relative (related person); Research; Research Personnel; Residencies; Role; Scientist; Staging; Stem cells; System; Systems Biology; Techniques; Testing; Therapeutic; Time; Tissues; Training; Training Programs; Trans-Activators; Transfusion; Transplantation; base; blastocyst; career; embryonic stem cell; gene function; insight; interest; knock-down; medical schools; mouse model; nerve injury; nerve stem cell; neurodevelopment; nuclear reprogramming; nuclear transfer; olfactory bulb; pluripotency; progenitor; programs; relating to nervous system; research study; skills; stem; stem cell fate; stem cell therapy; success; tool

DESCRIPTION (provided by applicant): This proposal describes a five-year training program aimed at developing research expertise that integrates neural, stem cell and systems biology. The applicant is a MD/PhD who will have completed pathology residency and clinical obligations for a transfusion medicine fellowship at Harvard Medical School prior to the proposed start date. The candidate's clinical interests are in the area of stem cell therapy, especially in the isolation, culturing, and manipulation of human somatic stem cells. He is currently receiving basic science training under the mentorship of Dr. Rudolf Jaenisch, a world-renowned expert on stem cells, cellular reprogramming, and developmental biology. Dr. Leslie Silberstein, head of the Harvard Transfusion Medicine program, will co-mentor the applicant during the proposed training period facilitating applicant's transition into an independent investigator. An advisory committee of highly respected physician and basic scientists will provide experimental insight and career guidance. The applicant is committed to an academic career in scientific research combining the skills he will develop as a researcher and clinician during the training period. The goal of the proposed research is to analyze the epigenetics of the neural stem cell fate and identify genes involved in the process. Neural stem cells hold great promise in the field of regenerative medicine including the treatment of neurodegenerative diseases and neural injury. However, very little is known about the biology of these cells. To maximize the clinical effectiveness of neural stem cells, it will be important to determine the nature of the genome that provides and at the same time limits their developmental potential. The candidate will use a combination of nuclear transfer techniques, expression and chromatin profiling, and functional testing of candidate genes in the mouse model system to address this problem. Nuclear transfer provides a global and unbiased method to reprogram the neural stem cell to a pluripotent state. Combined with expression and chromatin profiling, nuclear transfer can help identify candidate genes and epigenetic marks that determine the multipotent neural versus the pluripotent embryonic stem cell fate. Established genetic tools for ectopically expressing and knocking down gene function provide means to test the role of these candidate potency genes. This line of research should provide conceptual and therapeutic insight into means for altering stem cell fates for the amelioration of genetic and acquired neuropathologic disease.

描述（由申请人提供）： 该提案描述了一个为期五年的培训计划，旨在发展研究专业知识，整合神经，干细胞和系统生物学。申请人是一名医学博士/博士，在拟定的开始日期之前，已经完成了哈佛医学院输血医学奖学金的病理学住院医师和临床义务。候选人的临床兴趣是在干细胞治疗领域，特别是在分离，培养和操纵人体干细胞。他目前正在接受基础科学培训，导师是世界著名的干细胞、细胞重编程和发育生物学专家鲁道夫·耶尼施博士。哈佛输血医学项目负责人Leslie Silberstein博士将在拟议的培训期间共同指导申请人，以促进申请人转变为独立研究者。一个由德高望重的医生和基础科学家组成的咨询委员会将提供实验见解和职业指导。申请人致力于科学研究的学术生涯，结合他将在培训期间作为研究人员和临床医生发展的技能。这项研究的目的是分析神经干细胞命运的表观遗传学，并确定参与这一过程的基因。神经干细胞在再生医学领域有很大的应用前景，包括神经退行性疾病和神经损伤的治疗。然而，人们对这些细胞的生物学知之甚少。为了使神经干细胞的临床效果最大化，重要的是要确定提供并同时限制其发育潜力的基因组的性质。候选人将使用核转移技术，表达和染色质分析，以及在小鼠模型系统中候选基因的功能测试的组合来解决这个问题。核移植提供了一种全局和无偏的方法来将神经干细胞重编程为多能状态。结合表达和染色质分析，核移植可以帮助识别候选基因和表观遗传标记，决定多能神经与多能胚胎干细胞的命运。已建立的异位表达和敲低基因功能的遗传工具提供了测试这些候选效力基因的作用的手段。这一系列的研究应该提供概念和治疗的见解，改变干细胞的命运，改善遗传和获得性神经病理疾病的手段。