Gene regulation in phage lambda: A real-time study with single-event resolution

噬菌体 lambda 的基因调控：单事件分辨率的实时研究

基本信息

批准号：
7905902
负责人：
Ido Golding
金额：
$ 30.99万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-04 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7905902
关键词：
Active Biological Transport Affect Bacteria Bacteriophage lambda Bacteriophages Biochemical Biochemistry Biological Biological Models Capsid Cell Aging Cell physiology Cell surface Cells Characteristics Communities Complex Comprehension Cytolysis Cytoplasm DNA Damage Destinations Detection Development Diffusion Engineering Epigenetic Process Escherichia coli Eukaryota Event Fluorescence Microscopy Gene Expression Gene Expression Regulation Genetic Genetic Transcription Genome Goals Growth Hand In Vitro Individual Infection Kinetics Knowledge Life Life Cycle Stages Literature Location Lysogeny Lytic Lytic Phase Maintenance Measurement Measures Messenger RNA Methods Microscopic Modeling Motion Noise Organism Outcome Pathway interactions Phenotype Physiological Population Positioning Attribute Potential Energy Process Production Prokaryotic Cells Property Prophages Reaction Research Personnel Resolution Role Scientist Shapes Signal Transduction Source Spatial Distribution Staging System Systems Biology Theoretical model Time Time Study Transcript Virulent Virus base biological systems cell age cell injury chemical reaction developmental genetics in vivo insight lambda repressor macromolecule mathematical model molecular scale novel novel strategies public health relevance response self assembly spatiotemporal tool

项目摘要

DESCRIPTION (provided by applicant): The system comprised of the bacterium Escherichia coli and its virus, bacteriophage lambda, serves as the basic paradigm for many aspects of gene regulation, ranging in scale from the molecular to the organismic level. Questions asked within the lambda system often yield insights relevant to "higher" eukaryotic systems. The lambda system has been extensively characterized using the traditional tools of genetics and biochemistry, enabling the formation of an elegant and seemingly complete narrative of the observed phenomenology in terms of the microscopic interactions in the cell. However, from the point of view of a quantitative scientist there is an immense gap of understanding between the genetic and biochemical knowledge on the one hand, and the observed population phenotype on the other. This gap manifests itself in the poor predictive powers of mathematical models of the system. To try and bridge the knowledge gap it is required to "deconstruct" the life cycle of bacteriophage lambda by studying the events comprising this life cycle in real-time, in individual living cells, quantifying the intracellular dynamics with sufficient resolution to describe individual events in space and time. In this proposal we suggest to characterize gene regulation during the lambda life cycle, concentrating on the following aims: (1) Characterizing the function of the lysis/lysogeny switch during the maintenance of the lysogenic (dormant) state as well as the induction of the lytic (virulent) pathway following cell damage. (2) Elucidating spatiotemporal aspects affecting the life cycle, for example how the different stages of the lytic pathway genome replication, gene expression, capsid self-assembly and lysis are organized in space and time. (3) Distinguishing precision versus stochasticity in the lambda life cycle, by separating "real" stochasticity one resulting from actual sources of uncontrolled variability from "apparent" stochasticity, resulting from our own inability to detect and measure differences in physiological parameters between individual cells. PUBLIC HEALTH RELEVANCE: Filling the knowledge gap at the single-event level will in turn bring us closer to a quantitative understanding of whole-system (organism) characteristics in terms of the microscopic constituents, in the vain of "systems biology". Achieving this goal in a simple model system such as lambda can then be followed by similar endeavors in higher organisms.