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钟毅(Zhong Yi)博士

时间:2004-08-26 21:42来源:CSHL.EDU 作者:admin 阅读:


Yi Zhong
Associate Professor
Ph.D., University of Iowa, 1991
Neurophysiology; Drosophila; learning and memory; neurofibromatosis; signal transduction
email [email protected], phone (516) 367-6811, fax (516) 367-8880

We are interested in the neural basis of learning and memory. Currently, our research is confined to the following two areas:

First, we are establishing Drosophila models for studying neurogenetic disorders that impair learning and memory. Drosophila shares similar molecular mechanisms of learning and memory with vertebrates; and many of the genes identified in human diseases are evolutionarily conserved. Thus, Drosophila may serve as a useful model system for revealing functions of genes implicated in disease and lead to insights into pathogenesis and treatment. Mutations at the tumor suppressor neurofibromatosis 1 (NF1) gene cause neurofibromas and learning defects in patients, and mutations in the presenilin gene lead to early onset Alzheimer’s disease. Our electrophysiological, biochemical, and behavioral analyses of Drosophila NF1 mutants have revealed that the NF1 gene encodes a protein that functions as an inhibitor of Ras activity and also regulates the cAMP signal transduction pathway. This NF1-regulated cAMP pathway is crucial for learning in flies.

Second, we are using electrophysiological and optical methods for examining mechanisms of learning and memory at cellular and network levels in the Drosophila brain, which is particularly amenable to genetic manipulation. Currently, we are focusing on olfactory-related associative learning and have developed a preparation that allows us to monitor brain neural activity in response to odors and other stimuli in living flies. We are now investigating how odors are coded for and how such coding is modified during learning in a particular brain region called the “mushroom body”, known to be essential for olfactory-related learning.

博士,男,美国冷泉港实验室教授,清华大学生物系教授,教育部长江计划特聘教授。 
简 历:
  1982年毕业于清华大学工程物理系,获学士学位。
  1984年毕业于清华大学生物科学与技术系,获硕士学位。
  1985-1991年美国爱荷华大学(Iowa University)生物系,获博士学位,并接受博士后训练。
  1992年受聘到美国冷泉港实验室(Cold Spring Harbor Lab),任副教授,2001年晋升为教授。
  2001年被聘为清华大学生物系讲座教授,博士生导师。同年被聘为教育部长江计划特聘教授。
主要科学贡献:
  首次发现突触传递的易化和强刺激后的强化与基因缺陷有关。发现PACAP神经多肽,PKA等能挽救神经纤维瘤基因(Neurofibromatosis 1, NF-1)缺失突变体的学习记忆能力,并阐明其胞内分子代谢途径,在学习记忆的神经生物学基础研究方面取得突破性进展,为疾病的临床治疗和药物开发提供了有价值的依据。
研究领域及方向:
  以果蝇为模型,在行为、细胞和分子水平对学习记忆的神经生物学机制进行研究。目前的工作主要集中在下面两个领域:
  (1)影响学习记忆的神经系统疾病。在分子水平,果蝇与脊椎动物具有相同的学习记忆机理,许多人类的疾病基因在果蝇身上有高度的保守性。所以可以利用果蝇研究许多人类的致病基因。目前的工作集中在神经纤维瘤(neurofibromatosis 1, NF1 )和早老基因( presenilin)。NF1是一种肿瘤抑制基因。它的突变导致神经纤维瘤,而且病人的学习记忆功能缺陷;NF1蛋白抑制Ras蛋白的活性,并且在cAMP信号传导通路中起调节作用。早老基因的突变导致阿尔兹海默病的发病时间提前。
  (2)利用电生理和双光子显微镜,在细胞和神经网络水平研究果蝇脑的学习记忆机制。当前的研究集中在果蝇的嗅觉联合式学习记忆,我们建立了一套果蝇脑神经元信号记录装置,可以记录活体果蝇大脑对气味以及其它刺激的反应。在嗅觉学习记忆相关脑区“蘑菇体”,研究了气味信号在脑内如何编码以及信号在学习过程中被修饰的过程。我们的目标是建立基因-脑-行为的理论框架,解决脑功能的复杂机理,为人类脑疾病的治疗寻找途径。 

Selected Publications

Zhong, Y. 1995. Mediation of PACAP-like neuropeptide transmission by coactivation of Ras/Raf and cAMP signal transduction pathways in Drosophila. Nature 375: 588–592.

Guo, H.-F., I. The, F. Hannan, A. Bernards, and Y. Zhong. 1997. Requirement of Drosophila NF1 for activation of adenylyl cyclase by PACAP38-like neuropeptides. Science 276: 795–798.

The, I., G.E. Hannigan, G.S. Cowley, S. Reginald, Y. Zhong, J.F. Gusella, I.K. Hariharan, and A. Bernards. 1997. Rescue of Drosophila NF1 mutant phenotype by protein kinase A. Science 276: 791–794.

Guo, H.-F., J. Tong, F. Hannan, L. Luo, and Y. Zhong. 2000. A neurofibromatosis-1-regulated pathway is required for learning in Drosophila. Nature 403: 895–898.

Wang, Y., N.J.D. Wright, H.-F. Guo, Z. Xie, K. Svoboda, R. Malinow, D.P. Smith, and Y. Zhong. 2001. Genetic manipulation of the odor-evoked distributed neural activity in the Drosophila mushroom body. Neuron 29: 267–276.

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