Designer Molecular Probes for Biomedical Applications

项目摘要/摘要： 本文作者是宾夕法尼亚大学艾伦·麦克迪尔米德化学教授 2003年，他在那里启动了一个多学科研究计划，开发分子 在化学生物学、放射学、细胞学方面取得突破的探测 基因组学/转录学和麻醉学。在本研究的过程中，PI已经 指导博士后9人，研究生35人，本科生50人， 获得国家级奖项，大多数毕业生追求科学和生物医学的职业生涯。这个 Pi的研究借鉴了超分子有机化学的正规培训(哈佛-美因茨)， 生物无机化学和生物物理化学(加州理工学院博士)和生物学/生物分子成像 (加州理工学院博士后)。19年来，派在生物医学研究中的沉浸 宾夕法尼亚大学的企业学院为这种体验增添了光彩。通过关键协作，PI拥有 利用化学合成、蛋白质等工具，解决了重大的生物医学研究问题 以及寡核苷酸化学和生物分析化学。PI105的同行评议 出版物，7项专利，4本编辑书籍和贡献的书籍章节突出了 开发和应用中的生产力、创新、影响和传播 生物医学研究的化学工具。私家侦探的服务，包括目前在 SBCA研究科，确认对科学审查、教育、外联、 社区建设和初级教师指导。这个Mira奖极大地扩展了PI GM资助的三个项目领域的成功研究：1)使用氙气- 核磁共振造影剂；2)体内细胞转录组分析及mRNA调控 使用光激活的寡核苷酸探针；以及，3)全麻药蛋白的阐明 与新型荧光探针、超灵敏的129Xe核磁共振波谱等的相互作用 生物物理学方法。下一个五年计划的重要目标是完善这些调查- 以世界级研究为基础的技术-宾夕法尼亚大学的合作者并建立高价值 可广泛传播到生物医学研究社区的探头。总而言之， 这些工具将促进我们对正常生物/生物医学过程的分子理解 (包括全身麻醉)，并提供改善诊断和治疗的途径 许多人类疾病，包括癌症、神经变性和糖尿病。

Project Summary/Abstract: The PI is the Alan MacDiarmid Term Professor of Chemistry at the University of Pennsylvania (UPenn), where in 2003 he launched a multidisciplinary research program developing molecular probes that have led to breakthroughs in Chemical Biology, Radiology, Cellular Genomics/Transcriptomics, and Anesthesiology. In the course of this research, the PI has mentored 9 postdoctoral fellows, 35 graduate students, and 50 undergraduates, with many winning national awards and most graduates pursuing careers in science and biomedicine. The PI's research draws on formal training in supramolecular organic chemistry (Harvard-Mainz), bioinorganic and biophysical chemistry (Caltech, Ph.D.), and biology/biomolecular imaging (Caltech, postdoc). The PI's immersion for the past 19 years in the biomedical research enterprise at UPenn has burnished this experience. Through key collaborations, the PI has tackled significant biomedical research questions, using the tools of chemical synthesis, protein and oligonucleotide chemistry, and bioanalytical chemistry. The PI's 105 peer-reviewed publications, 7 patents, 4 edited books and contributed book chapters highlight a track record of productivity, innovation, impact, and dissemination in the development and application of chemical tools for biomedical research. The PI's service, including current membership on the SBCA study section, confirms a strong commitment to scientific review, education, outreach, community building, and junior faculty mentoring. This MIRA award extends the PI's highly successful GM-funded research in three program areas: 1) molecular imaging using xenon- based MRI contrast agents; 2) cellular transcriptome-in-vivo-analysis and mRNA regulation using light-activated oligonucleotide probes; and, 3) elucidation of general anesthetic-protein interactions with novel fluorescent probes, ultrasensitive 129Xe NMR spectroscopy, and other biophysical methods. Significant goals of the next five-year period are to refine these probe- based technologies with world-class research-collaborators at UPenn and establish high-value probes that can be disseminated broadly to the biomedical research community. Collectively, these tools will advance our molecular understanding of normal biological/biomedical processes (including general anesthesia), and provide avenues for improved diagnosis and treatment of many human diseases, including cancer, neurodegeneration, and diabetes.