THE CHEMICAL AND GENETIC BASIS OF INTERSPECIES INTERACTIONS
C Pieter
University Of California San Diegocity: La Jolla country: United States (us)
Grant 5R01AI095125-02 from National Institute Of Allergy And Infectious Diseases
Keywords: Affect; Analytical Chemistry; Anti-Bacterial Agents; Antibiotics; Antifungal Agents; Architecture; Attenuated; Bacillus subtilis; Bacteria; base; Behavior; Biological; biological adaptation to stress; Candidate Disease Gene; Cannibalism; cell behavior; Cell Density; cell motility; Cell Survival; Cells; Cessation of life; chemical genetics; Cytolysis; Data; Development; Environment; Enzymes; extracellular; Fluorescence Microscopy; fungus; Genes; Genetic; Genetic Screening; Growth; high throughput screening; Image; Imagery; imaging modality; Individual; Invaded; Killings; Libraries; Mass Spectrum Analysis; Mediating; Medicine; Methods; Movement; Mutagenesis; mutant; Outcome; Pathway interactions; Pharmaceutical Preparations; Pharmacologic Substance; Play; Population; Population Density; Predatory Behavior; Production; Pseudomonas aeruginosa; public health relevance; quorum sensing; Reporter Genes; research study; response; Role; Solid; Testing; Toxin; Use of New Techniques
Relevance: Bacteria produce many extracellular metabolites that mediate their interaction with other species, many of which have antibacterial and antifungal activities. We will here elucidate the chemical, genetic and cellular mechanisms by which these molecules allow Bacillus subtilis to interact with other bacterial species, producing outcomes ranging from coexistence to the invasion and destruction of neighboring colonies. Interspecies interactions are critical in medicine and the metabolites that facilitate destruction of other species represent promising new pharmaceutical leads
Project start date: 2011-03-07
Project end date: 2015-02-28
Budget start date: 1-MAR-2012
Budget end date: 28-FEB-2013
5R01AI095125-02 (2012): $593899
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to C Pieter
SYNAPT ION MOBILITY MASS SPECTROMETER
C Pieter, Professor/ph.d.
University Of California San Diegocity: La Jolla country: United States (us)
Grant 1S10RR029121-01 from National Center For Research Resources
Abstract: This proposal is for a Synapt ion mobility mass spectrometer and will be used for the characterization of therapeutics. The instrument is also used to characterize the effect of therapeutics on cellular processes and cell-to cell communication. This equipment will be used to train the future generation of Doctors of Pharmacy and PhD students engaged in drug development. Finally, the Synapt ion mobility mass spectrometer enables the discovery of the next generation therapeutics and therapeutic targets. This proposal is requesting funds for a mass spectrometry instrument that is to be used to uncover targets of disease and the discovery and characterization of novel therapeutics
Keywords: Cell Communication; Cell physiology; Cells; Disease; Doctor of Pharmacy; Doctor of Philosophy; drug development; Equipment; Funding; Future Generations; instrument; ion mobility; mass spectrometer; Mass Spectrum Analysis; novel therapeutics; public health relevance; Students; Therapeutic; Therapeutic Effect; therapeutic target; Training
Project start date: 2011-06-15
Project end date: 2012-06-14
Budget start date: 15-JUN-2011
Budget end date: 14-JUN-2012
PFA/PA: PAR-09-118
1S10RR029121-01 (2011): $802398
REAL-TIME IMAGING OF METABOLIC COMMUNICATION
C Pieter, Professor/ph.d.
University Of California San Diegocity: La Jolla country: United States (us)
Grant 5R01GM094802-02 from National Institute Of General Medical Sciences
Abstract: Metabolic exchange is a universal phenomenon. It is essential to every organism, from those as simple as bacteria to complex higher eukaryotes such as humans. While metabolic exchange enables cooperation and coordination between the ~70 trillion cells in an average human being, even unicellular organisms rely on metabolic exchange to adapt to environmental stress and form biofilms. Cellular communication allows stem cells to differentiate, cancer cells to proliferate, neurons to fire, bacteria to sense a quorum and pathogens to survive in human hosts. The chemical diversity of the molecules used for communication is extraordinary, and includes small ions such as calcium, small molecules such as secondary metabolites, fatty acids, peptides, but also carbohydrates, proteins and nucleic acids. Despite the universal nature of metabolic exchange, there are few methods that can characterize the communication between cells in a systematic and sensitive fashion, let alone real-time. In this proposal, our focus will be on the application and adaptation of desorption electrospray mass spectrometry to enable the real-time live cell detection and the characterization and visualization of metabolic exchange in important biological processes. We aim to accomplish this in both a spatial as well as temporal fashion. These tools will improve our understanding of secreted biomarkers, microbiome-human cell interactions and understanding the complexities of infectious disease that derive from the cooperation between different types of cells (e.g. Bacilli with macrophages, neutrophils or T-cells) and interkingdom communication. Ultimately it may drive the development of new therapeutic strategies or interventions based on paradigms involving inter-cellular metabolic communication in a system wide fashion. This proposal aims to develop real-time monitoring of molecular entities involved in metabolic exchange of pathogen-immunological cell populations. Our ability to "visualize" metabolic exchange between different cell populations could lead to new therapeutic paradigms
Keywords: Agar; Antibiotics; Bacillus (bacterium); Bacteria; base; Biological Factors; Biological Process; biomarker; Calcium; cancer cell; Carbohydrates; Cell Communication; Cell Culture Techniques; cell type; Cells; Chemicals; chemokine; Collagen; Communicable Diseases; Communication; Complex; Culture Media; cytokine; design; Detection; Development; Electrospray Ionization; Eukaryota; Fatty Acids; Fire - disasters; Growth; Guanine Nucleotide Exchange Factors; Human; Human Microbiome; Hydrogen Peroxide; Image; Imagery; Immune; Immune response; improved; Individual; interest; Intervention; ionization; Ions; Lead; Life; Lipids; macrophage; Mass Spectrum Analysis; Mediating; Metabolic; Methodology; Methods; Microbe; Microbial Biofilms; Molecular; Monitor; Morphology; Nature; Neurons; neutrophil; Nitric Oxide; novel therapeutics; Nucleic Acids; Organism; pathogen; Peptides; Polynucleotides; Population; potassium ion; Preparation; prevent; Process; Production; Proliferating; Proteins; Pseudomonas; public health relevance; quorum sensing; Sampling; Site-Directed Mutagenesis; small molecule; Solid; Solutions; Spatial Distribution; Staging; Stem cells; Stress; Structure; Supporting Cell; Surface; surface coating; System; T-Lymphocyte; Technology; Time; tool; Tumor Cell Line; Virulence Factors
Relevance: This proposal aims to develop real-time monitoring of molecular entities involved in metabolic exchange of pathogen-immunological cell populations. Our ability to "visualize" metabolic exchange between different cell populations could lead to new therapeutic paradigms
Project start date: 2010-09-01
Project end date: 2014-08-31
Budget start date: 1-SEP-2011
Budget end date: 31-AUG-2012
PFA/PA: RFA-GM-10-009
5R01GM094802-02 (2011): $269382
THE CHEMICAL AND GENETIC BASIS OF INTERSPECIES INTERACTIONS
C Pieter, Professor
University Of California San Diegocity: La Jolla country: United States (us)
Grant 1R01AI095125-01 from National Institute Of Allergy And Infectious Diseases
Abstract: Bacillus subtilis produces a wide array of extracellular metabolites that can inhibit the growth of bacteria and fungi or modify their behavior to attenuate the production of antibacterial products by potentially dangerous neighbors. We here propose to use the new technique of imaging mass spectrometry and classical analytical chemistry to systematically identify the extracellular metabolome of B. subtilis, with a focus on characterizing the interactive metabolome that is induced by other bacterial species. We will investigate the role these compounds play in two distinct outcomes of the interaction of B. subtilis with other species. The first is an impasse, in which B. subtilis forms closely abutting colonies with other species that produce a variety of antibacterial compounds (such as P. aeruginosa). The second, more frequent behavior is contact-dependent predation, in which B. subtilis moves towards, invades and destroys neighboring colonies, leading to death of the prey species and expanding the territory of the B. subtilis colony. These reproducible behaviors are conserved in different undomesticated B. subtilis strains. We will determine if these behaviors depend on the interactive metabolome and investigate the effects individual compounds have on target cell viability and behavior. We will further investigate the genetic requirements for interspecies interactions to identify stress responses, developmental and biosynthetic pathways that contribute to these distinct outcomes and we will use fluorescence microscopy to visualize the cellular consequences of interspecies interactions. These studies will illuminate the mechanistic basis for interspecies interactions and identify secondary metabolites that affect viability or behavior of other species that represent potential new antibacterial drugs. Bacteria produce many extracellular metabolites that mediate their interaction with other species, many of which have antibacterial and antifungal activities. We will here elucidate the chemical, genetic and cellular mechanisms by which these molecules allow Bacillus subtilis to interact with other bacterial species, producing outcomes ranging from coexistence to the invasion and destruction of neighboring colonies. Interspecies interactions are critical in medicine and the metabolites that facilitate destruction of other species represent promising new pharmaceutical leads
Keywords: Affect; Analytical Chemistry; anti-bacterial; Anti-Bacterial Agents; anti-fungal; antibacterial; Antibacterial Agents; Antibiotic Agents; Antibiotic Drugs; Antibiotics; Antifungal Agents; Antifungal Drug; antifungals; Architecture; Attenuated; Bacillus subtilis; Bacteria; base; Behavior; Biological; biological adaptation to stress; body movement; Candidate Disease Gene; Candidate Gene; Cannibalism; Cannibalisms; cell behavior; Cell Density; Cell Locomotion; Cell Migration; cell motility; Cell Movement; Cell Survival; Cell Viability; Cells; Cellular Migration; Cessation of life; chemical genetics; Chemistry, Analytic; Chemistry, Analytical; Cytolysis; Data; Death; Development; drug/agent; Drugs; Engineering / Architecture; Environment; Enzymes; experiment; experimental research; experimental study; extracellular; Fluorescence Microscopy; Fungicides, Therapeutic; fungus; Generalized Growth; Genes; Genetic; Genetic Screening; Genetics-Mutagenesis; Growth; High Throughput Assay; high throughput screening; human population density; Image; Imagery; imaging; imaging modality; Individual; Invaded; Killings; Libraries; Lysis; Mass Spectrum; Mass Spectrum Analysis; Mediating; Medication; Medicine; Methods; Microscopy, Fluorescence; Microscopy, Light, Fluorescence; Miscellaneous Antibiotic; Molecular Biology, Mutagenesis; Motility; Motility, Cellular; Movement; Mutagenesis; mutant; ontogeny; Outcome; P. aeruginosa; P.aeruginosa; pathway; Pathway interactions; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Preparations; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Photometry/Spectrum Analysis, Mass; Play; Population; Population Density; predation; Predatory Behavior; Production; Pseudomonas aeruginosa; Pseudomonas pyocyanea; public health relevance; quorum sensing; reaction; crisis; Reporter Genes; research study; response; Role; Science of Medicine; social role; Solid; Spectrometry, Mass; Spectroscopy, Mass; Spectrum Analyses, Mass; Spectrum Analysis, Mass; stress response; stress; reaction; Testing; Tissue Growth; Toxin; Use of New Techniques; Visualization
Relevance: Bacteria produce many extracellular metabolites that mediate their interaction with other species, many of which have antibacterial and antifungal activities. We will here elucidate the chemical, genetic and cellular mechanisms by which these molecules allow Bacillus subtilis to interact with other bacterial species, producing outcomes ranging from coexistence to the invasion and destruction of neighboring colonies. Interspecies interactions are critical in medicine and the metabolites that facilitate destruction of other species represent promising new pharmaceutical leads
Project start date: 2011-03-07
Project end date: 2015-02-28
Budget start date: 7-MAR-2011
Budget end date: 29-FEB-2012
PFA/PA: PA-10-067
1R01AI095125-01 (2011): $586317