METABOTROPIC GLUTAMATE RECEPTOR EXPRESSION AND FUNCTION

我目前是一名副教授(终身教授) 在乔治敦大学学习药理学，并在 费迪亚-乔治敦大学神经科学研究所。我的长期研究 目的是了解G蛋白偶联代谢型谷氨酸的作用 神经功能中的受体。我的职业目标是建立一个强大的 研究计划，并获得专业知识，使我能够结合 神经化学、药理学、细胞生物学和分子生物学技术 生物学研究受体功能表达和细胞内 发信号。 我在波兰学院神经化学系获得博士学位 1979年在华沙的科学学院。我的博士后培训 神经药理学与E·科斯塔博士一起在NIMH工作。我加入教职员工是在 乔治城大学成立于1985年，并在FGIN成立了 E·科斯塔博士的指导，药理学领域的研究计划 兴奋性氨基酸受体的信号转导。这项工作有 是我参加《激动人心》项目的基础 氨基酸：在中枢神经系统疾病中的作用“(P01-NS28130，R.A.Gillis，Program 董事)担任核心董事3年，并自1993年起担任主要董事 其中一个项目的调查员，该项目已于1998年3月31日获得资助。 提交当前的RCDA申请是为了使我能够扩展我的 在神经科学方面的专业知识，并将额外的时间投入到我的研究中 程序。通过减少我的教学和行政责任， 该奖项将允许个人在几个层面上和深入地成长 分子生物学和抗体制备技术方面的培训。 研究计划(基于资助的计划项目赠款)侧重于 代谢性谷氨酸受体(MGluRs)的表达和功能 神经元的原代培养。具体目标是：评估 肌醇磷脂(PI)偶联mGluRT的功能表达 通过确定信使核糖核酸表达的发育模式来进行水解， 受体蛋白，以及神经元PI反应的出现 在培养基中培养增强受体表达，并通过建立 这些受体的激动剂和拮抗剂药理学；确定 MGluRs通过鉴定特定底物和磷代谢在磷代谢中的作用 磷脂酶C的产物偶联mGluRs；以确定PI- 偶联mGluRs在细胞内钙稳态中的作用； 离子型谷氨酸受体(NMDA和AMPA)与受体相互作用的作用 MGluRs参与PI水解酶的调节。世界银行的一个重要目标 目前RCDA的应用是将拟议的研究扩展到整个 MGluRs家族，包括与腺苷环化酶负偶联的那些。 因此，我建议研究mRNA和受体蛋白的表达。 原代神经元培养中所有PI和cAMP偶联的mGluR 建立受体诱导反应的选择性药理学。 这些研究将为理解 MGluRs的药理和神经化学特性及其在脑内的作用 神经功能，以及未来治疗策略的发展。

I am currently an Associate Professor (tenure-track) in the department of Pharmacology at Georgetown University and hold a joint appointment in the Fidia-Georgetown Institute for the Neurosciences. My long-term research goal is to understand the role of G-protein coupled metabotropic glutamate receptors in neuronal function. My career goal is to establish a strong research program and gain expertise and knowledge allowing me to combine the techniques of neurochemistry, pharmacology, cell biology and molecular biology to study receptor functional expression and intracellular signalling. I obtained my Ph.D. from the Department of Neurochemistry, Polish Academy of Sciences in Warsaw in 1979. My postdoctoral training in neuropharmacology was with Dr. E. Costa at NIMH. I joined the faculty at Georgetown University in 1985 and have established at FGIN, under the direction of Dr. E. Costa, a research program in the field of pharmacology and signal transduction of excitatory amino acid receptors. This work has been the basis for my participation in the Program Project "Excitatory Amino Acids: Role in CNS Disorders" (P01-NS28130, R. A. Gillis, Program Director) for 3 years as a Core Director, and since 1993 as a principal investigator of one of the projects which has been funded through 3/31/98. The current RCDA application is submitted to enable me to expand my expertise in neurosciences and to devote additional time to my research program. By minimizing my teaching and administrative responsabilities, the award will allow for personal growth at several levels and for in-depth training in molecular biology an antibody preparation techniques. The research plan (based on the funded Program Project grant) focuses on the expression and function of metabotropic glutamate receptors (mGluRs) in primary cultures of neurons. The specific aims are: to evaluate the functional expression of mGluRTs coupled to phosphoinositide (PI) hydrolysis by determining the developmental pattern of expression of mRNA, receptor protein, and of the appearance of the PI response in neurons cultured in media enhancing receptor expression and by establishing the agonist and antagonist pharmacology of these receptors; to determine the role of mGluRs in PI metabolism by identifying the specific substrates and products of phospholipase C coupled to mGluRs; to determine the role of PI- coupled mGluRs in intracellular calcium homeostasis; and to determine the role of ionotropic glutamate receptors (NMDA and AMPA) interacting with mGluRs in the regulation of PI hydrolysis. An important goal of the current RCDA application is to extend the proposed studies to the entire family of mGluRs, including those negatively coupled to adenylate cyclase. Thus, I propose to study the expression of mRNA and receptor protein for all PI and cAMP-coupled mGluRs in primary neuronal cultures and to establish the selective pharmacology of the receptor-induced responses. These studies will provide information fundamental for the understanding of the pharmacological and neurochemical properties of mGluRs, their role in neuronal function, and for development of future therapeutic strategies.