Zhong Yi

Zhong Yi

Zhong Yi, male, born in Hunan in 1958, is a professor of School of life sciences of Tsinghua University and director of McGovern Institute of brain science.

In 1982, he graduated from the Department of Engineering Physics of Tsinghua University with a bachelor's degree. From 1982 to 1984, he studied in the Department of biological science and technology of Tsinghua University and obtained a master's degree. In 1991, he graduated from the Department of biological sciences of Iowa University with a doctorate in neurobiology. In 1992, he taught in the Department of neurobiology of Cold Spring Harbor Laboratory and led an independent laboratory. In 2001, he was promoted to Professor of Cold Spring Harbor Laboratory in the United States, and in the same year, he served as a professor of Tsinghua University. Since 2004, he has been the president of McGovern Brain Institute of Tsinghua University.

Profile

Zhong Yi:

1978-1982, Bachelor of Engineering Physics, Tsinghua University

1982-1984, master, Department of biological science and technology, Tsinghua University

1985-1991, doctor, Department of Biological Sciences, Iowa University, USA

1991-1992, postdoctoral, Department of Biological Sciences, Iowa University, USA

1992-1995, assistant researcher, Cold Spring Harbor Laboratory, USA

1992-2001, associate professor, Cold Spring Harbor Laboratory, USA

From 2001 to 2015, Professor of Cold Spring Harbor Laboratory and adjunct professor of School of life sciences, Tsinghua University

Since 2015, Professor, School of life sciences, Tsinghua University

Honor Award

1994-1997, "Pew" biomedical outstanding scholar Award for scientific contribution

Synaptic plasticity of Drosophila melanogaster was studied by using learning and memory mutants. It was found for the first time that synaptic facilitation and post tetanic enhancement could induce the change of synaptic activity in Drosophila melanogaster with cAMP signaling pathway defect. After independently running the laboratory in lengquangang, we first used Drosophila model to study human cognitive disorders, especially neurofibromatosis 1 (NF1) diseases. The results elucidate the new function of NF1 in signal transduction pathway, and find that NF1 is crucial for learning ability and long-term memory, thus laying a theoretical foundation for new treatment of NF1 disease. At the same time, it has also created a new research method of optical imaging analysis of neural activity in Drosophila brain, and is currently using this new technology to study the mechanism of neural coding formed by olfaction in learning and memory. The above work related papers have been published in science, nature and other journals, and obtained two U.S. patents.

In the laboratory of Tsinghua University, through the research of Drosophila molecular genetics and behavior, we have made important discoveries in the molecular mechanism of memory formation and forgetting, as well as the research of human neurodegenerative diseases and mental diseases. These achievements have been published in cell, PNAs, jneurosci and other journals.

Main research interests

1、 At the level of molecule, cell and neural network, the cellular and molecular mechanism of learning and memory is studied. It is mainly studied by behavioral, molecular, genetic, immunohistochemical and electrophysiological methods. At present, it mainly focuses on the following two aspects:

a. Analysis of the neural mechanism of learning and memory. Large scale olfactory behavior screening has been carried out on 1900 mutant lines of Drosophila, and 11 single gene mutants with specific olfactory memory defects have been identified. These mutants provide a new way to understand memory formation in the brain, and will use various methods to study how these gene mutations participate in the neural mechanism of learning and memory. Through these efforts, we first found that Notch, Yu, Ben, Chi and other genes are involved in the neural process of long-term memory formation in Drosophila. At the same time, we found that E3 ubiquitin linker HighWire negatively regulates the formation of long-term memory. Down regulation of HighWire protein can facilitate the formation of long-term memory. On the contrary, up regulation of HighWire protein can hinder the formation of long-term memory. Further studies show that HighWire and its DLK / JNK signaling pathway are specifically involved in the consolidation of long-term memory in the mushroom substructure of Drosophila melanogaster. These findings not only help us understand the neural basis of learning and memory, but also provide targets for screening new drugs to enhance human cognitive function.

b. The molecular mechanism of forgetting. In the process of learning and memory, the nervous system needs to actively complete the task of selecting important information and solidifying the long-term memory, and that part of the unselected information will naturally be forgotten, that is to say, if the newly formed memory fails to enter the solidifying stage, it will quickly disappear. This kind of forgetting is usually thought to come from the instability of new memory itself or the interference of irrelevant information. Although there have been many studies on the mechanism of the formation of fixed words in memory, little is known about the nature of forgetting. Recently, our laboratory combined molecular genetics and behavioral methods to explore the molecular mechanism of forgetting, and made a breakthrough in discovering the core role of small G protein Rac in the regulation of forgetting. It also indicates that the rearrangement of neuronal cytoskeleton may be the fundamental reason for the disappearance of memory, which provides enlightenment for people to understand the nature of forgetting.

2、 To study the cellular and molecular mechanism of nervous system diseases. It is mainly studied by behavioral, molecular, genetic, immunohistochemical and electrophysiological methods. At present, it mainly focuses on the following two aspects:

a. Molecular mechanism and drug screening of neurodegenerative diseases. Studies have shown that the expression of human Alzheimer's disease (AD) related peptide a β 42 in Drosophila can induce Drosophila to produce many symptoms similar to those of AD patients. This suggests that many of the molecular mechanisms of human cognitive disorders are also conserved in Drosophila. Therefore, the powerful molecular genetic model of Drosophila provides great convenience for revealing the molecular mechanism of complex brain diseases. At present, we have studied the mechanism of AD by means of behavioral, molecular, gene chip, electrophysiological and immunohistochemical methods. We found that overexpression of a β 42 in the brain of Drosophila melanogaster can lead to the abnormal up regulation of PI3K kinase activity, which leads to the obstacle of long-term inhibition, and eventually leads to age-dependent learning deficit; and the use of drug-specific inhibition of PI3K kinase activity can save the learning ability of Drosophila melanogaster. At the same time, we also used Drosophila model for large-scale AD drug screening, and have obtained a variety of lead compounds that can improve learning ability. Our research results not only provide a new molecular mechanism for the occurrence of AD, but also provide a target for the screening of therapeutic drugs.

b. Genetic and pathological mechanisms of complex mental disorders. The conservatism of genetic evolution, the convenience of genetic manipulation and the richness of behavioral paradigms make Drosophila a good research system for complex hereditary mental diseases, such as schizophrenia and autism. We found that the Drosophila homologous gene of dysbindin, a susceptible gene of schizophrenia, is involved in the regulation of glutamate and dopamine neurotransmitter systems and the corresponding behavioral phenotypes in neurons and glial cells through different molecular mechanisms. The genetic and pathological mechanisms of schizophrenia were analyzed from gene to neurophysiology and then to the overall behavior. In addition, we are also exploring the genetic mechanism of autism with Drosophila as a model system. These studies not only deepen our understanding of the disease mechanism, but also provide a basis for further drug screening.

Representative papers

1.ShuaiY,HuY,QinH,CampbellRA,ZhongY*.(2011)DistinctmolecularunderpinningsofDrosophilaolfact orytraceconditioning.ProcNatlAcadSciUSA108 :20201-20206.

2.ShaoL,ShuaiY,WangJ,FengS,LuB,LiZ,ZhaoY,WangL,ZhongY*.(2011)Schizophreniasusceptibilitygenedysbindinregulatesglutamatergicanddopaminergicfunctionsviadistinctiveme chanismsinDrosophila.ProcNatlAcadSciUSA108 :18831-18836.

3.ShuaiY,ZhangY,GaoL,ZhongY*.(2011)StressresistanceconferredbyneuronalexpressionofDominant-NegativeRacinadultDrosophilamelanogaster.J.Neurogenetics25(1-2):35-39.

4.ShuaiY,LuB,HuY,WangL,SunK,ZhongY*.(2010)ForgettingisregulatedthroughRac activityinDrosophila.Cell140 :579-89.

5.ChiangHC,WangL,XieZ,YauA,Zh

Chinese PinYin : Zhong Yi