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How Microbes Shape Their Communities? A Microbial Community Model Based on Functional Genes

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Genomics, Proteomics & Bioinformatics 2019年第1期17卷 91-105页

作者： Xiaoqing Jiang Xin Li Longshu Yang Chunhong Liu Qi Wang Weilai Chi Huaiqiu Zhu State Key Laboratory for Turbulence and Complex Systems Department of Biomedical Engineering College of Engineering Peking University Center for Quantitative Biology Peking University Peking University-Tsinghua University-National Institute of Biological Sciences Joint Biological (ptn) PhD program and College of Life Sciences Peking University Center for Protein Science Peking University

Exploring the mechanisms of maintaining microbial community structure is important to understand biofilm development or microbiota dysbiosis. In this paper, we propose a functional gene-based composition prediction(FCP) model to predict the population structure composition within a microbial community. The model predicts the community composition well in both a low-complexity community as acid mine drainage(AMD) microbiota, and a complex community as human gut microbiota. Furthermore, we define community structure shaping(CSS) genes as functional genes crucial for shaping the microbial community. We have identified CSS genes in AMD and human gut microbiota samples with FCP model and find that CSS genes change with the conditions. Compared to essential genes for microbes, CSS genes are significantly enriched in the genes involved in mobile genetic elements, cell motility, and defense mechanisms, indicating that the functions of CSS genes are focused on communication and strategies in response to the environment factors. We further find that it is the minority, rather than the majority, which contributes to maintaining community structure. Compared to health control samples, we find that some functional genes associated with metabolism of amino acids, nucleotides, and lipopolysaccharide are more likely to be CSS genes in the disease group. CSS genes may help us to understand critical cellular processes and be useful in seeking addable gene circuitries to maintain artificial self-sustainable communities. Our study suggests that functional genes are important to the assembly of microbial communities.

关键词： Metagenomics Dynamics model Community structure Acid mine drainage Human gut microbiota

Activity of dorsal raphe serotonin neurons signal reward and could drive fast neuroprosthetic learning

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Activity of dorsal raphe serotonin neurons signal reward and...

Phosphorylation of Atg31 is required for autophagy

中国神经科学学会第十届全国学术会议

作者： Jingfeng ZHOU Minmin LUO National Institute of Biological Sciences ptn Graduate program School of Life SciencesPeking University School of Life Sciences Tsinghua University

Objective Results from our lab have shown that photo-activation of dorsal raphe neurons produces strong reward and motivates rapid behavioral *** carried out recordings from behaving mice to address two related questions:（1） Whether DRN serotonin neurons encode reward signals;（2） whether the activity of DRN serotonin neurons could rapidly sculpt cortical neural *** DRN neurons were recorded in head-fixed mice that were being subjected to Go/No-go *** neurons were identified by optical *** combined the multi-channel recording technique with optogenetics to design a novel closed-loop brain machine interface（BMI） task to investigate how motor cortex neurons could be shaped by DRN serotonin ***（1） Many serotonin neurons in the DRN increased firing activity following rewarding stimuli.（2） Motor cortex neurons quickly changed their firing properties upon the BMI task *** Serotonin neurons in the DRN encode reward signals and their activation could induce rapid cortical remodeling.

关键词： dorsal raphe nucleus serotonin reward brain machine interface

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Protein & Cell 2015年第4期6卷 288-296页

作者： Wenzhi Feng Tong Wu Xiaoyu Dan Yuling Chen Lin Li She Chen Di Miao Haiteng Deng Xinqi Gong Li Yu ptn program College of Life Science Peking University Beijing 100871 China State Key Laboratory of Biomembrane and Membrane Biotechnology Tsinghua University-Peking University Joint Center for Life Sciences School of Life Sciences Tsinghua University Beijing 100084 China Center for Biomedical Analysis Tsinghua University Beijing 100084 China National Institute of Biological Sciences Beijing 102206 China Institute for Mathematical-Sciences Renmin-University of China Beijing 100872 China

Autophagy is an evolutionarily conserved cellular pro- cess which degrades intracellular contents. The Atg17- Atg31-Atg29 complex plays a key role in autophagy in- duction by various stimuli. In yeast, autophagy occurs with autophagosome formation at a special site near the vacuole named the pre-autophagosomal structure （PAS）. The Atg17-Atg31-Atg29 complex forms a scaffold for PAS organization, and recruits other autophagy-re- lated （Atg） proteins to the PAS. Here, we show that Atg31 is a phosphorylated protein. The phosphorylation sites on Atg31 were identified by mass spectrometry. Analy- sis of mutants in which the phosphorylated amino acids were replaced by alanine, either individually or in var- ious combinations, identified S174 as the functional phosphorylation site. An S174A mutant showed a simi- lar degree of autophagy impairment as an Atg31 deletion mutant. S174 phosphorylation is required for autophagy induced by various autophagy stimuli such as nitrogen starvation and rapamycin treatment. Mass spectrometry analysis showed that S174 is phosphorylated constitu- tively, and expression of a phosphorylation-mimic mu- tant （S174D） in the Atg31 deletion strain restores autophagy. In the S174A mutant, Atg9-positive vesicles accumulate at the PAS. Thus, S174 phosphorylation is required for formation of autophagosomes, possibly by facilitating the recycling of Atg9 from the PAS. Our data demonstrate the role of phosphorylation of Atg31 in autophagy.

关键词： autophagy Atg31 phosphorylation,autophagosome pre-autophagosomal structure (PAS)

Ciliopathy-associated proteins are involved in vesicle distribution in sensory cilia

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Journal of Genetics and Genomics 2019年第5期46卷 269-271页

作者： Ming Li Wanzhong He Wei Li Guangshuo Ou ptn Graduate program School of Life SciencesTsinghua UniversityBeijing100084China Tsinghua-Peking Center for Life Sciences School of Life SciencesTsinghua UniversityBeijing100084China National Institute of Biological Science BeijingW2206China National Institute of Biological Science Beijing102206China School of Medicine Tsinghua UniversityBeijing100084China Tsinghua-Peking Center for Life Sciences School of Life SciencesTsinghua UniversityBeijingW0084China

Cilia play a wide range of critical roles in regulating cell motility,sensory signaling and metazoan development(Goetz and Anderson,2010;Reiter and Leroux,2017).Both motile cilia and pri-mary cilia consist of a basal body and a microtubule-based axoneme that is encompassed within the ciliary *** formationand maintenance of ciliary structure depends on bidirectional intraflagellar transport(IFT):the kinesin-2 family motor proteins deliver ciliary precursors bound to the IFT particle protein complex from the ciliary base to the tip and the cytoplasmic dynein-2 recy-cles the anterograde IFT-protein machinery and ciliary turnover products back to the base(Scholey,2013;Reiter and Leroux,2017).Defects of ciliary structure and function lead to more than 35 types of systemic disorders in most human organ *** are collectively called ciliopathies(Reiter and Leroux,2017).187 established and 241 candidate ciliopathy-associated genes have been identified from the human genome(Reiter and Leroux,2017).

关键词： vesicle distribution sensory cilia

Analysis of phosphorylation sites on autophagy proteins

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Protein & Cell 2015年第9期6卷 698-701页

作者： Wenzhi Feng Wenhao Zhang Hui Wang Lili Ma Di Miao Zexian Liu Yu Xue Haiteng Deng Li Yu ptn program College of Life SciencePeking UniversityBeijing100871China Center for Biomedical Analysis Medical SchoolTsinghua UniversityBeijing100084China Key Laboratory of Cardiovascular Remodeling and Function Research Department of CardiologyQilu Hospital of Shandong UniversityJinan250012China Department of Biomedical Engineering College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China State Key Laboratory of Biomembrane and Membrane Biotechnology Tsinghua University–Peking University Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing100084China

Autophagy is a lysosome-based degradation pathway,characterized by formation of a double-membrane vesicle named the *** autophagy,various cargos are engulfed and delivered to lysosomes(or the vacuole in yeast)for *** is an evolutionarily conserved pathway and plays important roles in various physiological and pathological conditions such as develop-ment,immunity,cancer and neuronal degeneration(Jiang and Mizushima,2014;Martin et al.,2014).

关键词：蛋白磷酸化自噬位点分析降解途径溶酶体双层膜液泡进化

Development of a Deep Learning Model for Binding Affinity Prediction and Fragment-based de novo Drug Design

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Development of a Deep Learning Model for Binding Affinity Pr...

Activation of dorsal raphe neurons produces strong reward and guides rapid learning

中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Shiwei Wang Jianfeng Pei Luhua Lai ptn Joint Graduate program Academy for Advanced Interdisciplinary StudiesPeking University Center for Quantitative Biology Academy for Advanced Interdisciplinary StudiesPeking University BNLMS State Key Laboratory for Structural Chemistry of Unstable and Stable Speciesand Peking-Tsinghua Center for Life Sciences at College of Chemistry and Molecular EngineeringPeking University

The traditional drug design and discovery methods were time-consuming and expensive,which largely reduced the efficiency of drug design ***-based de novo drug design was applied to accelerate the procedure of drug *** a complementary of high-throughput screening technology,de novo drug design method is confronted with a virtually infinite search *** drug-like molecules can be discovered by exploring the chemical space with specific combinational search strategies,which provides a new approach to find novel ***,challenges including combinatorial explosion,scoring function and so on hinder the development and application of de novo drug *** this work,we hope to construct a reinforcement-learning model by combing Monto Carlo Tree Search method and deep neural network to solve the combinatorial explosion *** order to achieve our goals,we updated our Pocket program to extract more accurate pharmacophore models,which can help to extract features of 3 D structure information of protein-ligand ***,we developed a new scoring function to predict binding affinity of protein-ligand complex based on the 3 D structure *** further improving and optimizing,the new scoring function could be applied to binding affinity prediction and will be integrated to our fragment-based de novo drug design method.

关键词： scoring function Representation of binding pocket de novo drug design Reinforcement learning

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Activation of dorsal raphe neurons produces strong reward an...