SYSTEMS BIOLOGY OF SIGNAL CONTROL IN YEAST
Brent Roger
Vtt/msi Molecular Sciences Institutecity: Berkeley country: United States (us)
Grant 5R01GM086615-04 from National Institute Of General Medical Sciences
Keywords: Address; Affect; Animals; Behavior; Beryllium; Biological; Biological Process; biological systems; Biology; Carrying Capacities; Cell model; Cells; Clinical; Complex; Computers; Decision Making; Development; Developmental Biology; DNA; Dose; Electrons; Elements; Environment; Eukaryota; Event; Experimental Genetics; extracellular; Feedback; Foundations; G-Protein-Coupled Receptors; gene therapy; Genetic; Genome; Goals; GTP-Binding Proteins; Human; Individual; information model; Information Systems; insight; Interdisciplinary Study; Invertebrates; Investigation; Learning; Life; Ligands; Maps; Measurement; Measures; Methods; Mitogen-Activated Protein Kinases; Modeling; Molecular; Molecular Biology; Molecular Computations; Molecular Target; Nature; Noise; novel; Operating System; operation; Organism; Partner in relationship; Pathway interactions; Pharmaceutical Preparations; Pheromone; Physiological; Physiology; predictive modeling; protein function; Proteins; Proteomics; public health relevance; Reaction; receptor; Research; response; RGS Proteins; RNA; Saccharomyces cerevisiae; Saccharomycetales; Scaffolding Protein; Shapes; Signal Pathway; Signal Transduction; small molecule; Solutions; success; System; Systems Biology; Technology; Therapeutic Intervention; Time; tool; transmission process; Work; Yeasts
Relevance: Narrative Summary We will study the operation of one small part of a model information sensing and transmitting system in a model cell. We will learn how specific molecular operations regulate the signal and the information the signal transmits
Project start date: 2009-01-01
Project end date: 2012-12-31
Budget start date: 1-JAN-2012
Budget end date: 31-DEC-2012
5R01GM086615-04 (2012): $572206
Sponsored Links Excellgen http://Excellgen.com
SYSTEMS BIOLOGY OF SIGNAL CONTROL IN YEAST
Brent Roger
Molecular Sciences Institutecity: Berkeley country: United States (us)
Grant 5R01GM086615-03 from National Institute Of General Medical Sciences
Abstract: Living things differ from nonliving things in that they carry information stored in DNA and RNA. Much of what living cells need to do require them to integrate this stored information with information inputs from their external environments. In this way, cells are like computers, but, unlike computers, information handling by cells depends on molecules instead of electrons moving through wires. Over the past five years, we have developed and used advanced methods to study a very simple example of biological information handling, a system that a single yeast cell uses to sense and transmit information from outside to make decisions. We have learned about the molecules the cell uses to do this and some of the key operations these molecules perform. During the next five years, we will study carefully the molecular operations needed for one key portion of the information transmission system to function. We will learn how these molecular events affect the signal transmitted by the system and the information that the signal carries. In the shorter term, because closely related systems operate in all animal cells, including humans, what we learn about how the molecules operate may suggest avenues to devise drugs that manipulate their function and might afford useful therapies. Longer term, a better understanding of how molecular events perform operations on information may help guide genetic interventions, and might help contribute to development of molecular computation. We will study the operation of one small part of a model information sensing and transmitting system in a model cell. We will learn how specific molecular operations regulate the signal and the information the signal transmits
Keywords: Address; Affect; Animals; Be element; Be++ element; Behavior; Beryllium; Biological; Biological Function; Biological Process; biological signal transduction; biological systems; Biology; Carrying Capacities; Cell Communication and Signaling; Cell model; Cell Signaling; Cells; Cellular model; Clinical; Complex; computer based prediction; Computers; Decision Making; Deoxyribonucleic Acid; Development; Developmental Biology; DNA; DNA Molecular Biology; Dose; drug/agent; Drugs; EC 2.7.2-; Electrons; Elements; Endomycetales; Environment; Eukaryota; Eukaryote; eukaryotida; Event; Experimental Genetics; extracellular; Extracellular Signal-Regulated Kinases; Feedback; Foundations; G Protein-Complex Receptor; G-Protein-Coupled Receptors; G-Proteins; gene product; Gene Products, RNA; gene therapy; Gene Transfer Clinical; Gene Transfer Procedure; Gene-Tx; Genetic; Genetic Intervention; genetic therapy; Genome; Goals; GTP-Binding Proteins; GTP-Regulatory Proteins; Guanine Nucleotide Coupling Protein; Guanine Nucleotide Regulatory Proteins; Human; Human, General; Individual; Information Systems; Information Technology Systems; insight; Interdisciplinary Research; Interdisciplinary Study; intervention therapy; Intervention, Genetic; Intracellular Communication and Signaling; Invertebrata; Invertebrates; Invertebrates, General; Investigation; IT Systems; Learning; Life; Ligands; living system; Man (Taxonomy); Man, Modern; MAP kinase; MAPK; Maps; mate; Measurement; Measures; Medication; Methods; Mitogen-Activated Protein Kinases; Modeling; Molecular; Molecular Biology; Molecular Biology, Gene Therapy; Molecular Computations; Molecular Target; Multidisciplinary Collaboration; Multidisciplinary Research; Nature; Negative Beta Particle; Negatrons; Noise; novel; Operating System; operation; Organism; Partner in relationship; pathway; Pathway interactions; Pharmaceutic Preparations; Pharmaceutical Preparations; Pheromone; Physiologic; Physiological; Physiology; predictive modeling; protein function; Proteins; Proteomics; public health relevance; Reaction; receptor; Receptor Protein; Regulators of G-Protein Signaling Proteins; Research; response; RGS Family Protein; RGS Protein (G-Protein Signaling); RGS Proteins; Ribonucleic Acid; RNA; RNA, Non-Polyadenylated; S cerevisiae; Saccharomyces cerevisiae; Saccharomycetales; Scaffolding Protein; Shapes; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; small molecule; Solutions; Study, Interdisciplinary; success; System; System, LOINC Axis 4; Systems Biology; Systems, Data; Technology; Therapeutic Intervention; Therapy, DNA; Time; tool; Transmission; transmission process; Work; Yeast, Baker`s; Yeast, Brewer`s; Yeast, Budding; Yeasts
Relevance: Narrative Summary We will study the operation of one small part of a model information sensing and transmitting system in a model cell. We will learn how specific molecular operations regulate the signal and the information the signal transmits
Project start date: 2009-01-01
Project end date: 2012-12-31
Budget start date: 1-JAN-2011
Budget end date: 31-DEC-2011
PFA/PA: PA-07-070
5R01GM086615-03 (2011): $528292
Grants awarded to Brent Roger
DYNAMICS OF GRADIENT SENSING IN SINGLE CELLS
Brent Roger, Member
Fred Hutchinson Cancer Research Centercity: Seattle country: United States (us)
Grant 1R01GM097479-01 from National Institute Of General Medical Sciences
Abstract: Living systems use information about external conditions and information retrieved from their genomes to determine their future actions. The centrality of information in determining future behavior defines a key difference between biological systems and other complex physical systems. In metazoans, decision making in response to regulatory molecules in the extracellular environment is critical for development of the adult organism from the zygote and for maintenance of the adult soma. We therefore wish to understand how cells convert extracellular signals into quantitative measurements and how cells transmit and operate on this information. Our continuing studies of a prototypic cell signaling system, the Saccharomyces cerevisiae pheromone response system, have provided insights into these questions. Findings have come from experiments on single cells using engineered protein reporters and image cytometry to quantify molecular events in system operation. Although fruitful, the simplification required for these studies neglects a key aspect of metazoan signaling the extracellular regulatory molecules that orchestrate many key cell decisions are distributed in gradients. Gradients of regulatory ligand molecules are ubiquitous in vertebrates. The ability of vertebrate cells to correctly determine ligand concentration in gradients (for fate decisions), to correctly determine the ligand gradient vector (for polarity decisions), and to limit cell-to-cell variation in these determinations (for coherent responses by cell populations) is critical throughout development and adult life. Like vertebrate signaling systems, the prototype yeast system enables cells to read concentration and polarity vector of a ligand gradient. We will use the yeast system to understand the biophysical and molecular mechanisms cells use to determine concentration and polarity vector in gradients and that limit cell-to-cell-variation in these determinations. This work has been made possible by greatly increased single cell experimental abilities and recent development of microfludic devices allowing experimental observation of large numbers of cells in well-controlled gradients. During the next five years, for cells in gradients, we will elucidate biophysical and molecular mechanisms that bring about the speed and accuracy of concentration determination, that enable quick and accurate gradient determination, and that make the responses of cell populations more coherent by restricting cell-to-cell variation in these determinations. A mechanism-based quantitative understanding of how cells make these determinations and limit cell-to-cell variation in them would advance basic knowledge and would likely suggest paths to manipulate particular quantitative behaviors in order to achieve therapeutic ends. This work will help us understand how cells read amounts and directions of signal molecules in gradients, and how groups of cells respond coherently by reading these the same way. In multicellular animals, including humans, these processes are critical for development of the adult from the fertilized egg, for maintenance of the adult body (as cells in tissues die and new ones replace them), and during development of cancers (particularly solid tumors). Understanding will guide future basic research and may suggest paths for therapeutic interventions
Keywords: Adult; Animals; Antineoplastic Agents; base; Basic Science; Behavior; Binding (Molecular Function); biological systems; cell body (neuron); Cell Count; Cell Nucleus; Cell physiology; Cells; Collection; Complex; Data; Decision Making; design; Development; Devices; Drug Delivery Systems; Environment; Equilibrium; Eukaryota; Event; extracellular; Future; G-Protein-Coupled Receptors; Genetic; Genome; Haploid Cells; Human; Image Cytometry; insight; Knowledge; Life; Ligand Binding; Ligands; Maintenance; Malignant Neoplasms; Measurement; Measures; Molecular; Morphogenesis; neglect; Operating System; operation; Organism; Orthologous Gene; Partner in relationship; Pharmacotherapy; Pheromone; Physiological; Population; Process; Protein Engineering; prototype; public health relevance; Publishing; Reading; receptor; receptor binding; Reporter; research study; response; Saccharomyces cerevisiae; sex; Side; Signal Transduction; Signaling Molecule; Solid Neoplasm; Speed (motion); Structure; System; Therapeutic; Therapeutic Intervention; Tissues; Translations; Variant; vector; Vertebrates; Work; Yeasts; zygote
Project start date: 2011-04-18
Project end date: 2015-03-31
Budget start date: 18-APR-2011
Budget end date: 31-MAR-2012
PFA/PA: PA-10-067
1R01GM097479-01 (2011): $568567