Программа Школы будет состоять из лекций и секционных докладов ведущих ученых, сообщений молодых ученых (с конкурсом лучших работ), постерной сессии, а также практических занятий, включая научные секции по направления.
Содержание лекций (на английском) представлено ниже.
Секция: БИОЛОГИЯ РАЗВИТИЯ И СТВОЛОВЫЕ КЛЕТКИ
Секция посвящена актуальным проблемам системной биологии, связанным с современными технологиями получения и применения стволовых клеток, методами их системного компьютерного анализа. Исследование свойств стволовых клеток, способных к самообновлению и развитию в специализированные клетки организма, — фундаментальная основа лечения многих тяжелых заболеваний, регенеративной клеточной медицины. Тотипотентная зигота, способная дать начало всем специализированным клеткам, и каждая специализированная клетка организма несут один и тот же набор генетической информации, однако эта информация реализуется по разным программам. Во взрослом организме стволовые клетки находятся, в основном, в костном мозге. Они обеспечивают восстановление поврежденных участков органов и тканей, могут восстановить практически любое повреждение, превращаясь на месте в необходимые организму клетки (костные, гладкомышечные, печеночные, сердечной мышцы, нервные) и стимулируя внутренние резервы организма к регенерации (восстановлению) органа или ткани. Можно ли управлять этими программами и применять это для лечения самых разных заболеваний, какие компьютерные модели применимы для этого в настоящее время – эти вопросы будут представлены на данной сессии. Методы системной биологии в применении к моделям раннего развития, эмбриональным стволовым клеткам (ЭСК) и индуцированным плюрипотентным стволовым клеткам (ИПСК) будут рассмотрены вместе с методами биоинформатики и экспериментальными подходами.
Секция: НЕЙРОБИОЛОГИЯ И КОГНИТИВНЫЕ ПРОЦЕССЫ
Будут рассмотрены актуальные проблемы нейробиологии и нейроинформатики, дан обзор текущего состояния когнитивных наук, компьютерных моделей высшей нервной деятельности. Вопросы нейробиологии включают такие направления как гибридные нейроэлектронные системы, полномасштабный анализ экспрессии генов в мозге, нейронные сети. Будет рассказано о мировых результатах в данных областях и перспективных работах нейробиологии, связанных с лечением болезни Альцгеймера. Ключевыми лекциями будут доклады, посвященные актуальным проблемам нейробиологии, молекулярным механизмам памяти, компьютерным моделям восприятия информации.
В последние десятилетия в результате исследований мозга накоплено огромное количество данных о процессах, протекающих в нервных клетках на молекулярно-генетическом и клеточном уровнях. Современные методы анализа экспрессии генов в тканях мозга, мультиэлектродной регистрации нейрональной активности, оптической флуоресцентной визуализации с каждым днем открывают все больше возможностей для исследования тонких механизмов работы нервных клеток. В ходе работы сессии будет дан обзор текущего состояния экспериментально-компьютерных методов нейробиологии, представлены компьютерные модели нейрона.
Секция: ПРОИСХОЖДЕНИЕ И ЭВОЛЮЦИЯ ЧЕЛОВЕКА
Данная секция посвящена вопросам происхождения и эволюция человека в контексте новейших открытий археологии и палеогеномики. Будут рассмотрены методы биоинформатики для анализа древней ДНК, проблемы исследование геномов гоминид и современного человека, исследование Homo Denisova.
Секция: БИОИНФОРМАТИКА И АНАЛИЗ ГЕНОМНЫХ ДАННЫХ
Изучение регуляции экспрессии генов является ключевым как для понимания механизмов функционирования живых организмов, так и выявления закономерностей развития клеток и органов, в том числе нейронов и мозговой ткани.
Биоинформатика и системная биология регуляции экспрессии генов оказывается все более захватывающей в свете развития высокопроизводительных методов секвенирования нового поколения, обеспечивающих исследователей значительными массивами ценнейших данных нового типа, таких, как глобальное профилирование модификаций хроматина, полногеномные профили ДНК-белковых взаимодействий (ChIP-seq), полное профилирование транскриптома, полногеномное картирование SNP. Вопросы получения, эффективной обработки и интеграции данных являются ключевыми для решения задач регуломики, которым будут посвящены доклады на этой сессии.
ПРАКТИЧЕСКИЕ РАБОТЫ –
Данный блок будет посвящен анализу экспрессии генов, работе с базами данных, что также представлено в лекциях на научных сессиях. Новые, высокопроизводительные методы секвенирования (NGS) кардинально трансформируют современные биологические исследования, обеспечивая быстрое секвенирование полных геномов организмов и предоставляя возможности исследования геномных ассоциаций (GWAS), секвенирования индивидуальных геномов. Встают задачи компьютерной сборки (ассемблирования) полных геномов de novo, аннотирования полного транскриптома клеток, тканей и организмов (технология RNAseq).
Содержание лекций
Лекция 1
Pluripotent stem cells
Prof. S.L. Kiselev, M.A. Lagarkova, A.N. Bogomazova, M.V. Shutova, E. Nekrasov, V. Naumov, D. Ischenko, E. Kaznacheeva, V. Vigont (N.I. Vavilov Institute of General Genetics, Moscow, Russia)
Stem cells and specifically induced pluripotent stem cells (iPSCs) hold enormous promise for the development of novel cell-based therapies as well as for the creation of model systems to study diseases and develop new pharmaceuticals. However, realization of iPSCs potential requires significant advances in biology. In this presentation we will discuss functional markers of reprogramming process with the emphasis on chromatin remodeling. We will show how genome wide methylome and transcriptome analysis combined with bioinformatics approaches generate specific markers that distinguish iPSCs from their “gold standard” embryonic stem cells and determine their fate. Finally, we demonstrate how differentiated iPSCs can be used for the disease modeling and new drugs screening.
Лекция 2
Embryonic stem cells: origin and properties
Prof. O.L. Serov (ICG SB RAS, Novosibirsk)
The lecture gives overview of origin and properties of human and mouse embryonic stem (ES) cells. Differences in timing in human and mouse early development determine various in pluripotency between human and mouse ES cells. During in vitro cultivation some ES cells can acquire additional pluripotency comparable to embryos at 2-cell stages.
Лекция 3
New methods of genome editing in pluripotent stem cells
S.P. Medvedev, S.M. Zakian (ICG SB RAS, Novosibirsk)
Pluripotent cells are a unique model for fundamental studies of the processes taking place during early embryogenesis in human and animals. In addition, the cells can be used in human diseases modeling and substitutive cell therapy. Discovery of the phenomenon of induced pluripotency and development of induced pluripotent stem cell derivation methods allowed making a serious progress in this area. However, new effective methods of genome editing of pluripotent cells are necessary to be developed for their large-scale application in fundamental studies and personalized and translational medicine. To date using TALEN artificial nucleases and CRISPR/Cas9 system for directed genome editing are of great interest. Prospects and problems of their application for generating cell models of inherited human diseases and editing gene mutations in patient-specific cells will be discussed.
Лекция 4
Information content of signal molecule: humoral code
Prof. N.N. Dygalo (ICG SB RAS, Novosibirsk)
The lecture is devoted to the problem of origin and function of tissue factors, neurotransmitters and hormones
Лекция 5
Variability and robustness in biological systems
Prof. M.G. Samsonova (St.Petersburg State Polytechnic University, St.Petersburg)
Variability in biological processes is observed on multiple scales and stems from different origins. Biological systems have evolved means to buffer unpredictable variation. In spite of intensive studies over the past decade, the mechanism of canalization and biological robustness remains controversial. In this talk I am going to discuss mechanisms that provide for robustness of pattering in fruit fly.
Лекция 6
Studying long QT syndrome using patient-specific induced pluripotent stem cells
E.V. Dementieva, Zakian S.M. (ICG SB RAS, Novosibirsk)
Long QT syndrome is a disease detected as a prolongation of the QT interval on electrocardiogram. Long QT syndrome leads to an increased risk of ventricular tachycardia, which can cause syncope, ventricular fibrillation, and sudden death. To date a good model to study the disease and to search for effective methods of its treatment has not been developed. Induced pluripotent stem cells are a new approach in cell biology, which has broad prospects of application in human diseases modeling and therapy. A potential use of induced pluripotent stem cells for long QT syndrome studying and treatment will be considered and some authors’ results will be described.
Лекция 7
Directed vascular differentiation of human stem cells for application in engineering of vascular grafts
Dr. I.S. Zakharova, Shevchenko A.I., Zakian S.M. (ICG SB RAS, Novosibirsk)
We have been established a reproducible protocol of directed differentiation of human embryonic stem cells to multipotent vascular progenitors. The main idea of the protocol consists in the use of collagen type IV and factors VEGF, BMP4 and bFGF. The developed approach allowed us to get a VEGF R2-positive population of vascular progenitor cells up to 93% of vs. 15% in previously available protocols. A further differentiation of VEGF R2-positive progenitors reveals their ability to give rise to both endothelial and mural derivates that have appropriate markers and are suitable for application in engineering of vascular grafts.
Лекция 8
3D organization of stem cell genome
Battulin N.R. (ICG SB RAS, Novosibirsk)
The 3D organization of an eukaryotic genome plays an important role in nuclear gene expression. The development of chromosome conformation capture (3C) methods allowed studying genome-wide chromosomal contacts by using only molecular methods. Nowadays, numerous 3C-based methods have been developed to reconstruct the 3D organization of eukaryotic chromosomes in nucleus. We consider example of 3D organization of mouse stem cells chromosomes.
Лекция 9
Molecular, cellular and systemic neuroscience of memory
Prof. K.V. Anokhin (Department of Neuroscience, National Research Center «Kurchatov Institute» Moscow; Laboratory of Neurobiology of Memory, P.K. Anokhin Institute of Normal Physiology, Moscow)
Consciousness and memory are tightly linked in neural mechanisms of subjective experience. We have previously shown that memory consolidation involves neuronal expression of immediate-early genes (IEGs) (Maleeva et at., 1989) that can be used to map memory assemblies in the brain (Anokhin, 1989). Behavioral induction of IEGs is triggered by subjective novelty of experience (Anokhin & Sudakov, 1993) and occurs during establishment of single-trial episodic-like memories (Anokhin et al., 1991; Ryabinin & Anokhin, 1993). At the level of neuronal activity it is associated with experience-dependent specialization of neuronal responses (Svarnik et al., 2005). In extension of this line of research I propose that imaging of behaviorally induced expression of IEGs can be used to trace episodes of conscious experience in the nervous system. With this purpose we developed techniques to visualize activation of IEGs during behavior by employing GFP transgenic reporter mice (Anokhin et al., 2012), methods for optical clearing of a whole mouse brain after behavioral episodes of induction of IEGs (Efimova & Anokhin, 2009) and whole brain cell-resolution optical fluorescent tomography technique to image experience-driven distributed functional systems by IEGs expression (Morozov et al., 2010). I further suggest that linking IEGs promoters with optogenetic toolkit will be instrumental for causal analysis of neural bases of subjective experiences, allowing to operate with cognitively indexed neuronal circuits in vivo.
Лекция 10
The molecular mechanisms of Alzheimer’s disease
Prof. E.I. Rogaev (University of Massachusetts Medical School, Massachusetts, USA)
Лекция 11
Neuroscience in the XXI Century: How can we study language and mind?
Prof. T.V. Chernigovskaya (St.Petersburg State University, St.Petersburg; National Research Center «Kurchatov Institute»)
Human cognition came after human anatomy and was based on it. We need human neuronal mirror system for language and social interaction, still more – for learning itself: it codes actions, sounds, gestures, face and voice qualities to express emotions allowing us to understand intentions of other people, etc. The ability to observe and comment our own behavior is a basis for reflection – probably the only human specific mental feature left accepted after years of anthropological and ethological studies of cognitive faculties. Human specific complex hierarchical language with phonological ‘atoms’ and recursion in syntax developed since autonomous vocal language has arisen, that needed mighty computation and working memory sub-served by specialized cerebral patterns. Modern neurolinguistic paradigms and techniques allow to study language and mind experimentally.
Лекция 12
The molecular function of the neuron cognitive reactions
Prof. A.S. Ratushyak (Design Technological Institute of Digital Techniques SB RAS, Novosibirsk)
Analysis of a cell as a multilevel functional system component that interacts in a wide range of time and space allows us to conceptualize the processes of the origination of integrative properties of nerve cells associated with the concepts of cognition. The protein-protein network reflects the molecular functional system of a spine in a state of «readiness» perception and action for change of synaptic connectivity using its own resources. Based on the conceptual model of a neuron that takes into account the basic properties of simulation systems development it may be revealed the functional capabilities of such systems in their biologic prototypes, thus creating the opportunity for medicine to correct the pathologic states involving the cognitive impairment.
Лекция 13
Neuroinformatics. Mathematical models of learning neuron, the functional systems and animat models
Prof. E.E. Vityaev (Sobolev Institute of Mathematics SB RAS, Novosibirsk)
Formal models of neuron, perception and functional system are presented. They are based on solution of some problems of artificial intelligence and the law of nature – causality. All these models considered at the neural level. Some animats are developed based on these formal models. In particular, A.Demin is developed the control system of hook-worm C. elegans that is solving the chemotaxis problem and moving just as a real organism.
Лекция 14
Genetics of personality traits and aggressive behavior
Prof. E.K. Khusnutdinova (Ufa Institute of Biochemistry and Genetics, Ufa Scientific Centre of Russian Academy of Sciences, Ufa, Russia)
Personality traits are the complex phenotypes influenced by both environmental and genetic factors (account for 40-60 % of the variance) and are assumed to be the endophenotypes of psychopathologies. Existing psychobiological models, personality traits relation to functioning of different neurotransmitter, neurotrophic factors, tachykininergic, neurexin, hypothalamic-pituitary-adrenal and arginin-vasopressin systems, genome-wide linkage and genome-wide association studies, as well as our data involving 320 SNPs from 36 genes in 1018 individuals, GxE and GxG models are discussed. Personality traits modulate genetic predisposition to aggressive behavior. The involvement of three neurobiological systems genes and environmental factors in the pathophysiology of aggressive behavior, genome-wide association studies, as well as our findings including genetic risk markers of suicidal behavior and GxG models are demonstrated. Future directions and limitations to genetic studies of personality and aggressive behavior are reported
Лекция 15
Human origin and evolution
Dr. A.S. Pilipenko, Prof. V.I. Molodin (Institute of Archeology and Ethnography SB RAS, ICG SB RAS, Novosibirsk)
Лекция 16
High throughput sequencing and computer analysis of molecular evolution on example of Homo Denisova genome
K.V. Gunbin, N.A. Kolchanov (ICG SB RAS, Novosibirsk)
A computer assisted study of genomes of primates, ancient and modern humans has shown that pre-miRNA with fixed functionally important substitutions regulate mRNAs expressed in brain structures crucial for speech development and in the organs of the female reproductive system.
Лекция 17
Gene Geography and Ethnography
Prof. N.K. Yankovsky (Vavilov Institute of General Genetics RAS, Moscow)
Understanding of functional role of millions SNPs in the human genome is one of the most challenging goals of human genome study nowadays. One of the new approaches to meet the goal is to search for correlations between geographic distributions of population allele frequencies and specificity of environmental conditions in the areas inhabited by the populations. The information is contained in many different types of databases (genetic, ethnographic, archeological etc.) electronic included. Some correlations between genetic and environmental data were found and leaded to create hypotheses on adaptive role of some SNPs in the human genome. The hypotheses are of interest from evolutionary, historical and medical point of views.
Лекция 18
Modeling of transport process in biological systems
Prof. A.M. Samsonov, S.A. Rukolaine (Ioffe Physical Technical Institute, St.-Petersburg)
Comparative analysis of different models of mass transfer in biological systems will be discussed. We consider some disadvantages in conventional reaction-diffusion description of transport processes in biological systems, and propose to generalize the diffusion model to the 2nd order telegraph equation and to the Jeffreys type equation of the 3d order. Fundamental solutions to both generalizations will be considered, and biological importance of a new approach will be discussed.
Лекция 19
Towards a microRNA interactome network
Prof. M. Chen (Zhejiang University, Hangzhou, China)
In order to discover novel miRNAs or other small RNAs (sRNAs), and their target genes we established a new framework with adjustable parameters of current available algorithms for reverse identification of miRNA—target pairs in plants. Based on our expertise on plant sRNAs, genome sequencing and bioinformatics, we plan to conduct a comprehensive study of the plant sRNAs in animals, in particular the miRNAs that can lead to cross kingdom regulation of genes.
Лекция 20
Protein 3D-structure homology modeling based on their amino acid sequence. Myths and Realities
Dr. N.N. Vtyurin (Moscow)
Due to the fast development of genome sequencing technologies the problem of new genomes annotation is becoming more and more acute. One of the most important annotation stages is determination of 3D-structure of proteins encoded by the new genome. Experimental methods for determining the 3D structure of protein molecules (X-ray diffraction and nuclear magnetic resonance) cannot cope with the exponentially growing demand. In its report, the author analyzes and discusses the possibility of using Protein 3D-structures homology modeling based on their amino acid sequence to solve or to soft (at least partially) this problem.
Лекция 21
Building computer simulation of C. elegans nematode to investigate its nervous system: results and perspectives
Dr. Palyanov A.Y. (A.P. Ershov Institute of Informatics Systems SB RAS, Novosibirsk)
C. elegans is one of the most well-studied multicellular organisms, consisting of 959 cells, 302 of which are neurons, but we still don’t know fundamental principles underlying neuroinformational processes in it. The lecture will include the description of the international collaboration of C. elegans researchers named OpenWorm, aimed to build the first comprehensive computational model of the C. elegans, our latest results illustrated by computer demonstrations, as well as future plans and perspectives.
Лекция 22
New sequencing technologies and transcriptome analysis
Prof. A.V. Kukekova, L.N.Trut, Yu.E. Herbeck (ICG SB RAS, Novosibirsk, Russia; University of Illinois, USA)
We discuss transcriptome analysis of “tame” and “aggressive” foxes from lines selected by long time behavior experiments at the Institute of Cytology and Genetics SB RAS. The lines strongly differ by aggressive reaction on human and present perspective model to study mechanisms of social behavior. We used transcriptome sequencing of prefrontal cortex of the foxes by Life Sciences Roche 454 and Illumina HiSeq technologies.
Лекция 23
Model adaptation using Differential Evolution Entirely Parallel method
Dr. K.N. Kozlov (St.Petersburg State Polytechnic University, St.Petersburg)
Currently, the design of efficient algorithms and systems to solve the inverse problem of mathematical modeling continues to be a challenge due to large volume and heterogeneity of biomedical data, as well as high computational complexity of biomedical applications. A considerable enhancement is proposed for the Differential Evolution Entirely Parallel (DEEP) method developed recently. The Differential Evolution was introduced in 1995 by Storn and Price. We demonstrate the application of enhanced DEEP method to the problem of finding parameters of mathematical model of biological system using several objective functions. The software is available from http://sourceforge.net/projects/deepmethod/
Лекция 24. практическое занятие
Computer databases for genome data analysis
Dr. Y.L. Orlov, D.A. Afonnikov (ICG SB RAS, Novosibirsk)
Analysis of genome data needs integration of databases on next generation sequencing, gene expression and gene functional annotation. We consider examples of whole-genome sequencing data processing using tools and databases from UCSC Genome Browser, ENCODE project, NCBI and Ensembl.
Лекция 25. практическое занятие
Design and analysis of genetic association networks. Computer system ANDVisio
Dr. Tiys E.S. (ICG SB RAS, Novosibirsk)
We discuss Associative Network Discovery (AND) System. The system allows automated extraction of knowledge about molecular-genetic interactions in cell from scientific literature and databases using text-mining and data-mining approaches. ANDVisio is a tool for reconstruction of semantic associative networks. The AND system allows user to automatically reconstruct gene networks associated with some gene, protein, metabolite, miRNA, disease, pathway or cellular component.
Выездное заседание программного комитета Школы «ПЕРСПЕКТИВЫ СИСТЕМНОЙ БИОЛОГИИ, ЭТНО- И ПАЛЕОГЕНОМИКИ»
Заседание посвящено проблемам преподавания системной биологии и биоинформатики. Будет рассмотрены вопросы новых научных дисциплин – этногеномики и палеогеномики, связанных с геномными исследованиями и секвенированием древней ДНК, эволюционным анализом гоминид и современного человека, применением методов молекулярной биологии и биоинформатики.