Jorge E Galan
Yale University
Project start date: 1991-01-01
Project end date: 2015-06-30
Sponsored Links Excellgen http://Excellgen.com
MOLECULAR GENETIC ANALYSIS OF SALMONELLA CELL INVASION
Jorge E Galan, Professor And Chairman
Yale University 47 College Street, Ste 203 New Haven, Ct 065208047
Grant 5R01AI030492-11 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Central to the pathogenicity of all Salmonellae is their ability to gain access to host cells that are normally non-phagocytic. Despite recent important advances in the understanding of the interaction of Salmonella with host cells, the mechanisms of entry as well as the bacterial determinants that trigger this process remain poorly characterized. We have been studying a Salmonella genetic locus, inv, that is required for bacterial entry into non-phagocytic cells. The extension of the molecular and functional characterization of this locus is the focus of this Grant proposal. It is now clear that the inv locus encodes a dedicated, sec- independent, type-Ill protein secretion system presumably required for the surface presentation of factors necessary for the entry process or for the biogenesis of a supramolecular structure involved in the delivery of entry determinants. This secretion system, which is also present in other bacterial pathogens, is different from the type I sec-independent system exemplified by the export of the E. coli hemolysin or the type II sec-dependent export pathway exemplified by the secretion of pullulanase, an enzyme of the gram negative organism Klebsiella oxytoca. Although proteins whose export depends on the function of type III systems have been identified in several microorganisms (e. g. Shigella Epee s and Yersinia Yops), only one such proteins, InvJ, has been so far identified in Salmonella. Identification of targets of this secretion apparatus is of great interest since it may lead to the identification of putative Salmonella effector molecules that trigger bacterial uptake. Our long term objective is to understand the molecular bases of Salmonella entry. In particular, our specific aims are 1) to conduct a functional analysis of the protein secretion system encoded in the inv locus; 2) to identify additional targets of this export system; and 3) to investigate their putative effector functions on the host cell.
Keywords: Salmonella, host organism interaction, molecular genetics, molecular pathology, pathologic process, bacterial DNA, bacterial genetics, bacterial protein, disease model, gene mutation, intermolecular interaction, protein signal sequence, protein transport, genetic manipulation, laboratory mouse, laboratory rabbit, recombinant DNA, scanning electron microscopy, site directed mutagenesis, western blotting
Project start date: 1991-01-01
Project end date: 2000-06-30
5R01AI030492-11 (1999): $297088
5R01AI030492-09 (1998): $286389
5R01AI030492-08 (1997): $228287
5R01AI030492-07 (1996): $219508
Grants awarded to Jorge E Galan
THE TYPE III SECRETION EFFECTOR PROTEIN INTERACTOME
Jorge E Galan, Professor And Chairman
Yale University, 47 College Street, Ste 203, New Haven, Ct 06520-8047
Grant 5R21AI072516-02 from National Institute Of Allergy And Infectious Diseases
Abstract: Type III protein secretion machines are widely distributed among many bacteria pathogenic and symbiotic for animals, plants and insects, and are essential for the pathogenic or symbiotic life style of the bacteria that encode them. These machines exert their function by "injecting" a battery of bacterial proteins into host-eukaryotic cells with the capacity to modulate a variety of cellular functions. The function of the vast majority of TTSS effector proteins is completely unknown. From studies on a very limited number of effectors, the theme that has emerged as central for the function of most of these virulence factors is one of "mimicry" of eukaryotic cell proteins. This "mimicry" most often cannot be detected at the level of amino acid sequence similarity but emerges after detail functional and structural analysis of the complexes between the target proteins and the bacterial effectors. Therefore, the understanding of the function of TTSS effectors proteins will require the identification of the proteins and cellular processes they target within the host cell. The availability of "systems-based approaches" to the study of biological processes is revolutionizing biomedical research. We propose to apply one of such high-throughput approaches to carry out a large-scale analysis of the interaction between TTSS effector proteins from bacteria pathogenic from humans and the entire human cell proteome. More specifically, we propose 1) To assemble a comprehensive list of TTSS effector proteins from bacteria pathogenic for humans pathogens and assay their potential interaction with the human ORFeome using a high-throughput yeast-two-hybrid system; 2) To verify the interaction of a selected group of effectors with a variety of biochemical and functional assays; and 3) To connect the TTSS effector proteins to the human protein-protein interactome network to model type III secretion function during bacterial infection. It is expected that these studies will provide an extremely useful resource for the understanding of the pathogenesis of many important bacterial diseases
Keywords: Amino Acid Sequence; Animals; Assay; Bacteria; Bacterial Gene Proteins; Bacterial Infections; Bacterial Proteins; Bioassay; Biochemical; Biologic Assays; Biological Assay; Biological Function; Biological Process; Biomedical Research; Cell Function; Cell Process; Cell physiology; Cells; Cellular Function; Cellular Physiology; Cellular Process; Communities; Complex; Data Banks; Data Bases; Databank, Electronic; Databanks; Database, Electronic; Databases; Deposit; Deposition; Eukaryote; Eukaryotic Cell; Gene Products, Bacterial; Human; Human, General; Insecta; Insects; Invertebrates, Insects; Investigators; Life Style; Lifestyle; Link; Man (Taxonomy); Man, Modern; Modeling; Numbers; Pathogenesis; Pathogenicity Factors; Plants; Plants, General; Programs (PT); Programs [Publication Type]; Protein Secretion; Protein Structure, Primary; Proteins; Proteome; Research; Research Personnel; Research Resources; Researchers; Resources; Speed; Speed (motion); Subcellular Process; System; System, LOINC Axis 4; Two Hybrid; Virulence Factors; Yeast One Hybrid System; Yeast One/Two-Hybrid System; bacterial disease; base; clinical data repository; clinical data warehouse; data repository; eukaryotida; gene product; mimicry; pathogen; pathogenic bacteria; programs; protein sequence; relational database; yeast two hybrid system
Project start date: 2007-09-20
Project end date: 2010-08-31
Budget start date: 1-SEP-2008
Budget end date: 31-AUG-2010
PFA/PA: PA-04-119
5R21AI072516-02 (2008): $0
1R21AI072516-01 (2007): $288895
PREDOCTORAL TRAINING PROGRAM IN MICROBIAL PATHOGENESIS
Jorge E Galan
Yale University, 47 College Street, Ste 203, New Haven, Ct 06520-8047
Grant 5T32AI007640-10 from National Institute Of Allergy And Infectious Diseases
Abstract: This application is a request for continuation of support for a predoctoral training program in Microbial pathogenesis at Yale University. The goal of this program is to train students in multidisciplinary approaches to the study of microbial pathogenesis. The training faculty shares the view that the understanding of the biology of pathogenic microorganisms requires experimental approaches and concepts from different fields of science. Therefore the program seeks to provide students with the necessary broad experimental skills and knowledge that will allow them to pursue a future research career in the study of microbial pathogens. The existence of very strong basic science departments committed to this concept coupled to the recent launching of the Section of Microbial Pathogenesis at the Yale School of Medicine creates a unique environment in which this training program can flourish and produce superbly trained scientists. The training program consists of formal course work and laboratory rotations during the first two years. This provides a solid and broad conceptual foundation and knowledge base as well as broad experimental training through the laboratory rotations. Students select a research advisor during the second year and prepare and defend a research proposal that will serve as the foundation for the dissertation research project. A Thesis committee monitors the student progress throughout the thesis research process and, finally, the preparation of the dissertation. Students enter the program through the Combined Program in Biological and Biomedical Sciences (BBS). The BBS unites the more than 200 faculty in basic biological and biomedical sciences at the Yale Medical School and Science Hill on the main University Campus. Admission is granted to students with outstanding academic record with particular attention to research experience. The training Faculty hold primary appointments in different basic science as well as clinical Departments and carry out research in a broad range of topics that are directly relevant to microbial pathogenesis. This breath gives student unique opportunities to explore different aspects of microbial pathogenesis research. Trainees are also provided with multiple opportunities for scientific interactions not only within the home Department but throughout Yale University
Keywords: Pathogenesis; Training Programs; microbial; pre-doc; pre-doctoral; predoc; predoctoral
Project start date: 2000-08-01
Project end date: 2011-08-31
Budget start date: 1-SEP-2010
Budget end date: 31-AUG-2011
PFA/PA: PA-02-109
5T32AI007640-10 (2010): $226168
5T32AI007640-09 (2009): $218566
5T32AI007640-08 (2008): $216076
5T32AI007640-07 (2007): $223192
2T32AI007640-06A1 (2006): $211814
HOST CELL SIGNALING PATHWAYS INDUCED BY SALMONELLA
Jorge E Galan, Professor And Chairman
Yale University, 47 College Street, Ste 203, New Haven, Ct 06520-8047
Grant 5R01AI055472-17 from National Institute Of Allergy And Infectious Diseases
Abstract: Salmonellosis continues to be a major worldwide health concern. Essential to the pathogenicity of these bacteria is the coordinated activities of two type III protein secretion systems (TTSS), which direct the translocation into host cells of a battery of bacterial effector proteins that modulate a variety of cellular processes. Work in our laboratory supported by this Grant has focused on the study of the cell biology of the complex functional interface between Salmonella enterica and host cells, and in particular the study of the function of several Salmonella TTSS effector proteins. This research project is aimed at deepening our understanding of the cell biology of the Salmonella/host interactions, and the function of TTSS effector proteins whose role in the infection process is poorly understood. It is hoped that these studies will facilitate the development of novel immunological and pharmacological strategies to prevent diseases caused by all Salmonella enterica serovars. Furthermore, the paradigms of host-pathogen interactions established by these studies may also help the understanding of the pathogenesis of other important pathogens, which have evolved close associations with their hosts. Salmonella enterica, which causes food poisoning and typhoid fever in humans, continues to be a very significant health problem. It is estimated that there are 1.3 billion cases of Salmonella infections every year leading to 3 million annual deaths. Knowledge gained from this research should help develop novel therapeutic and prevention strategies
Keywords: Actins; Amino Acid Sequence; Apoptosis; Apoptosis Pathway; Bacteria; Bacterial Infections; Body Tissues; Cell Communication and Signaling; Cell Death, Programmed; Cell Function; Cell Process; Cell Signaling; Cell physiology; Cells; Cellular Function; Cellular Matrix; Cellular Physiology; Cellular Process; Cellular biology; Cessation of life; Complex; Cytoskeletal System; Cytoskeleton; Death; Development; Disease; Disorder; Enteric Fever; Epithelial Cells; Eukaryote; Eukaryotic Cell; Food Poisoning; Funding; Gene Expression; Grant; Gut Inflammation; Health; Host Defense Mechanism; Human; Human, General; Immune response; Infection; Inflammatory Diseases of the Intestinal Tract; Inflammatory disease of the intestine; Inflammatory disorder of the intestine; Intestinal; Intestinal Inflammation; Intestines; Intracellular Communication and Signaling; Knowledge; Laboratories; Man (Taxonomy); Man, Modern; Pathogenesis; Pathogenicity; Pathogenicity Factors; Pathogenicity Island; Prevention strategy; Preventive strategy; Principal Investigator; Process; Programs (PT); Programs [Publication Type]; Protein Secretion; Protein Structure, Primary; Proteins; R01 Mechanism; R01 Program; RPG; Research; Research Grants; Research Project Grants; Research Projects; Research Projects, R-Series; Role; S. enterica; Salmonella; Salmonella enterica; Salmonella infections; Salmonellosis; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; Spi-1; Subcellular Process; System; System, LOINC Axis 4; Tissues; Two Hybrid; Type III Secretion System; Type III Secretion System Pathway; Typhoid; Typhoid Fever; Typhoids; Typhus, Abdominal; Virulence Factors; Work; Yeast One Hybrid System; Yeast One/Two-Hybrid System; bacterial disease; biological signal transduction; bowel; cell biology; disease/disorder; eukaryotida; gene product; host response; immunoresponse; intracellular skeleton; lambda Spi-1; new therapeutics; next generation therapeutics; novel; novel therapeutics; pathogen; prevent; preventing; programs; protein sequence; public health relevance; social role; trafficking; yeast two hybrid system
Project start date: 1995-05-01
Project end date: 2013-04-30
Budget start date: 1-MAY-2010
Budget end date: 30-APR-2011
PFA/PA: PA-07-070
5R01AI055472-17 (2010): $582754
5R01AI055472-16 (2009): $599502
5R01AI055472-14 (2007): $554012
Sponsored Links Excellgen http://Excellgen.com
5R01AI055472-13 (2006): $555362
5R01AI055472-12 (2005): $553621
5R01AI055472-11 (2004): $538896
9R01AI055472-10 (2003): $523200
HOT CELL SIGNALING PATHWAYS INDUCED BY SALMONELLA
Jorge E Galan, Professor And Chairman
State University New York Stony Brook Stony Brook, Ny 11794
Grant 5R01GM052543-04 from National Institute Of General Medical Sciences IRG: BM
Abstract: Salmonellosis continues to be a major world-wide health problem. Although Salmonella infections (other than typhoid fever) are usually self limiting, in immunocompromised individuals (e.g. elderly and AIDS patients) non- typhoid Salmonella can cause life threatening disease. S. typhi infections remain a very series problem in third world countries, particularly in children under the age of three. An essential pathogenic feature of all Salmonella spp. is their ability to gain access to mammalian cells that are normally non-phagocytic. The internalization process is the result of an intimate interaction between the bacteria and the host cell which results in the induction of signal transduction pathways that lead to membrane ruffling and bacterial internalization. Another feature of Salmonella infections is that the pathology of this disease is largely due to the host response to the invading pathogen. Little is known about the mechanisms by which Salmonella induces host responses but it is our hypothesis that signal transduction pathways evoked by Salmonella at the host cell surface may lead to the activation of transcription factors with subsequent production of biologically active molecules (e.g. cytokines, eicosenoids). These molecules may in turn modulate both the inflammatory as well as the immune response of the host to these organisms. Recent work from our laboratory has begun to outline the signaling pathways evoked by Salmonella in host mammalian cells. However, mere work is needed to better defined those pathways as well as to understand the Salmonella-induced host cellular mechanisms that lad to the activation of transcription factors. it is an objective of this research project to use a variety of genetic, biochemical and cell biological techniques to define more precisely the host cell signal transduction pathways evoked by Salmonella resulting in bacterial uptake. In addition, we intend to identify nuclear responses evoked by Salmonella that may lead to the activation of transcription factors and subsequent production of modulators of the inflammatory or immune responses. Although we will initially use S. typhimurium in our experiments, the results obtained are likely to be extrapolatable to all Salmonella serotypes and may help to define new concepts around which new drugs can be designed that may help to prevent infections by Salmonella or other intracellular pathogens.
Keywords: Salmonella, biological signal transduction, cell cycle protein, enzyme activity, gene expression, guanine nucleotide binding protein, immunoglobulin G, interleukin 6, nuclear factor kappa beta, phospholipase A2, transcription factor, 3T3 cell, tissue /cell culture, western blotting
Project start date: 1995-05-01
Project end date: 1998-06-30
5R01GM052543-04 (1998): $209308
5R01GM052543-03 (1997): $201256
MOLECULAR GENETIC ANALYSIS OF SALMONELLA CELL INVASION
Jorge E Galan, Professor And Chairman
Yale University, 47 College Street, Ste 203, New Haven, Ct 06520-8047
Grant 5R37AI030492-21 from National Institute Of Allergy And Infectious Diseases
Abstract: Salmonellosis continues to be a major world-wide health concern. Essential to the pathogenicity of Salmonella enterica is the function of a type III secretion system encoded within a pathogenicity island (SPI- 1) of its chromosome. This system mediates the delivery into the host cell of bacterial effector proteins which stimulate host cell responses including actin cytoskeleton rearrangements leading to bacterial uptake, production of pro-inflammatory cytokines, and the initiation of programmed cell death in macrophages. Previous work in our laboratory has focused on the characterization of the structural components of this secretion system, the identification of associated proteins that aid the secretion process, and the identification of secreted proteins that stimulate or interfere with cellular responses. We have also established that some of the components of the type III secretion apparatus are organized in a supramolecular structure, the needle complex, that spans the bacterial envelope and resembles the flagellar basal body. The proposed research project, a natural extension of the previous studies, is aimed at gaining a better understanding of the function of the centisome 63 type III secretion system of Salmonella enterica. More specifically we propose!) To study the composition of the type III secretion-associated needle complex structure; 2) To establish the assembly pathway of the type III secretion-associated needle complex; 3) To investigate the function of InvC, the type III secretion-associated ATPase that is presumed to energize the secretion machinery; 4) To identify the signals that allow the recognition of different secreted proteins by the secretion apparatus; and 5)/To investigate the regulatory function of SicA, a type III secretion-associated chaperone. These studies will enhance our understanding of the interaction of Salmonella with host cells. Since type HI secretions systejms are present in several important pathogenic bacteria, these studies may also help the development of novel antimicrobial drugs potentially effective against many bacterial pathogens
Keywords: ATP phosphohydrolase; ATPase; Actins; Adenosine Triphosphatase; Adenosinetriphosphatase; Apoptosis; Apoptosis Pathway; Cell Communication and Signaling; Cell Death, Programmed; Cell Signaling; Cells; Cellular Matrix; Chaperone; Chromosomes; Complex; Computer Assisted; Cryo-electron Microscopy; Cryoelectron Microscopy; Cytoskeletal System; Cytoskeleton; DNA Sequence Rearrangement; Development; Dose; Electron Cryomicroscopy; Genes; Genetic analyses; Health; Imagery; Inflammatory; Intracellular Communication and Signaling; Investigation; Laboratories; Mediating; Molecular Chaperones; Molecular Genetic; Molecular Genetics; Needles; Pathogenicity; Pathogenicity Island; Pathway interactions; Process of secretion; Production; Protein Secretion; Proteins; R01 Mechanism; R01 Program; RPG; Rearrangement; Research Grants; Research Project Grants; Research Projects; Research Projects, R-Series; S. enterica; S. typhimurium; S.typhimurium; Salmonella; Salmonella enterica; Salmonella infections; Salmonella typhimurium; Salmonellosis; Signal Transduction; Signal Transduction Systems; Signaling; Spi-1; Structure; System; System, LOINC Axis 4; Type III Secretion System; Type III Secretion System Pathway; Visualization; Work; anti-microbial agent; anti-microbial drug; antimicrobial agent; antimicrobial drug; basal body; base; biological signal transduction; computer aided; cryoEM; cytokine; gene product; genetic analysis; intracellular skeleton; kinetosome; lambda Spi-1; macrophage; novel; null mutation; pathogen; pathogenic bacteria; pathway; response; secretion process; transcription factor; uptake
Project start date: 1991-01-01
Project end date: 2010-06-30
Budget start date: 1-JUL-2009
Budget end date: 30-JUN-2010
PFA/PA: PA-03-080
5R37AI030492-21 (2009): $452427
5R37AI030492-20 (2008): $442380
HOST CELL SIGNALING PATHWAYS INDUCED BY SALMONELLA
Jorge E Galan, Professor And Chairman
Yale University 47 College Street, Ste 203 New Haven, Ct 065208047
Grant 5R01GM052543-09 from National Institute Of General Medical Sciences IRG: ZRG1
Abstract: Salmonellosis continues to be a major world-wide health concern. Central to the pathogenicity of Salmonella enterica is its ability to engage host cells in an intimate two-way biochemical interaction. The centerpiece of this interaction is a type III protein secretion system encoded at centisome 63 of its chromosome. This system directs the translocation into the host cell of several bacterial effector proteins that stimulate a variety of cellular responses including actin cytoskeleton rearrangements, membrane ruffling, macropinocytosis, activation of transcription factors and, in some cell types such as macrophages, the stimulation of program cell death. These responses are critical for pathogenicity as they allow the bacteria to gain access to host cells, avoid host defense mechanisms and reach deeper tissues. In addition, they contribute to the establishment of the inflammatory diarrhea that most often ensues Salmonella infections by stimulating the production of pro-inflammatory cytokines. Work in our laboratory supported by this Grant has focused on the study of the cell biology of these Salmonella-host cell interactions. During the last funding period we established that central to these responses is the function of the small molecular weight GTP- binding protein CDC42. Through different downstream effectors that remain largely unidentified, this G protein orchestrates both actin cytoskeleton rearrangements resulting in bacterial entry, as well as the activation of transcription factors leading to cytokine production. Our understanding of this process has been helped greatly by the identification of the actual bacterial effectors that trigger these responses after their delivery through the type III secretion system. The proposed research project is aimed at gaining a better understanding of the cell biology of the cellular responses induced by Salmonella enterica as well as a more thorough understanding of the mechanism of action of the different bacterial effector proteins. More specifically we propose 1) To define the role of different CDC42 downstream target effector proteins in the Salmonella-induced nuclear and cytoskeletal responses; 2) To investigate the function of the S. typhimurium effectors SipA, SopE, SopB, and SptP which are delivered into the host cell via the centisome 63 type III secretion system; and 3) To initiate studies to investigate the potential in-vivo role of signaling molecules during bacterial infection. These studies will advance the understanding of the cell biology of Salmonella enterica infections and facilitate the development of novel immunological and pharmacological strategies to prevent diseases caused by all Salmonella enterica serovars including S. typhi.
Keywords: Salmonella, biological signal transduction, host organism interaction, cytokine, gene expression, gene mutation, guanine nucleotide binding protein, laboratory mouse, polymerase chain reaction, tissue /cell culture, transgenic animal
Project start date: 1995-05-01
Project end date: 2003-04-30
5R01GM052543-09 (2002): $503220
5R01GM052543-08 (2001): $493337
Sponsored Links Excellgen http://Excellgen.com
5R01GM052543-07 (2000): $483739
MOLECULAR GENETIC ANALYSIS OF SALMONELLA CELL INVASION
Jorge E Galan, Professor And Chairman
Molecular Genetics & Microbiolstate University New York Stony Brook
stony Brook, Ny 11794
Grant 5R29AI030492-04 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Salmonellosis continues to be a major health problem in the United States and the rest of the world. Penetration of intestinal epithelial cells is a common feature of all Salmonella species. Despite the central importance of this event in the pathogenicity of these organisms, little is known about its molecular bases. The broad objective of this study is to understand the molecular mechanisms of Salmonella invasion of non- phagocytic cells and to identify all the biochemical components involved in this interaction. The principal investigator has recently cloned a group of genes (invA, B, C and D) that allow S. typhimurium to penetrate tissue culture cells. The functional study of these genes by a combination of biochemical, tissue culture and genetic techniques will be the main focus of this research. Mutated inv genes will be introduced into wild-type S. typhimurium to determine their specific role in invasion to cultured epithelial cells. The localization of the inv gene products in the bacterial cell as well as their ability to bind to eukaryotic cells will be examined. Fusions to reporter genes will be employed to examine the regulation of expression of the inv genes in response to exposure to tissue culture cells as well as to other environmental influences. The role of DNA supercoiling in this context will be particularly examined using in vivo and in vitro techniques. Mutations that affect expression of the inv genes will be isolated to characterize regulatory loci. Additional pathways of Salmonella invasion to tissue culture cells will be sought by isolating invasion defective mutants and characterizing the mutated loci. The studies proposed will increase the understanding of the molecular bases of Salmonella invasion to non-phagocytic cells. This knowledge will in turn facilitate the developing of new strategies to prevent and treat diseases caused by these and other invasive bacteria
Keywords: Salmonella infection, Salmonella typhimurium, bacterial DNA, host organism interaction, molecular genetics Salmonella, Salmonella typhi, antibody, fusion gene, gene expression, gene mutation, genetic mapping, genetic regulation, genetic transcription, genetic translation, nucleic acid structure, reporter gene Escherichia coli, genetic manipulation, laboratory mouse, laboratory rabbit, microorganism genetics, molecular cloning, nucleic acid sequence, tissue /cell culture, transfection
Project start date: 1991-01-01
Project end date: 1995-12-31
5R29AI030492-04 (1994): $123280
MOLECULAR GENETIC ANALYSIS OF SALMONELLA CELL IN
Jorge E Galan, Professor And Chairman
State University New York Stony Brook
stony Brook, Ny 11794
Grant 5R29AI030492-03 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Salmonellosis continues to be a major health problem in the United States and the rest of the world. Penetration of intestinal epithelial cells is a common feature of all Salmonella species. Despite the central importance of this event in the pathogenicity of these organisms, little is known about its molecular bases. The broad objective of this study is to understand the molecular mechanisms of Salmonella invasion of non- phagocytic cells and to identify all the biochemical components involved in this interaction. The principal investigator has recently cloned a group of genes (invA, B, C and D) that allow S. typhimurium to penetrate tissue culture cells. The functional study of these genes by a combination of biochemical, tissue culture and genetic techniques will be the main focus of this research. Mutated inv genes will be introduced into wild-type S. typhimurium to determine their specific role in invasion to cultured epithelial cells. The localization of the inv gene products in the bacterial cell as well as their ability to bind to eukaryotic cells will be examined. Fusions to reporter genes will be employed to examine the regulation of expression of the inv genes in response to exposure to tissue culture cells as well as to other environmental influences. The role of DNA supercoiling in this context will be particularly examined using in vivo and in vitro techniques. Mutations that affect expression of the inv genes will be isolated to characterize regulatory loci. Additional pathways of Salmonella invasion to tissue culture cells will be sought by isolating invasion defective mutants and characterizing the mutated loci. The studies proposed will increase the understanding of the molecular bases of Salmonella invasion to non-phagocytic cells. This knowledge will in turn facilitate the developing of new strategies to prevent and treat diseases caused by these and other invasive bacteria
Keywords: Salmonella infection, Salmonella typhimurium, bacterial DNA, host organism interaction, molecular genetics Salmonella, Salmonella typhi, antibody, fusion gene, gene expression, gene mutation, genetic mapping, genetic regulation, genetic transcription, genetic translation, nucleic acid structure, reporter gene Escherichia coli, genetic manipulation, laboratory mouse, laboratory rabbit, microorganism genetics, molecular cloning, nucleic acid sequence, tissue /cell culture, transfection
Project start date: 1991-01-01
Project end date: 1995-12-31
5R29AI030492-03 (1993): $119306
MOLECULAR GENETIC ANALYSIS OF SALMONELLA CELL INVASION
Jorge E Galan, Professor And Chairman
State University New York Stony Brook Stony Brook, Ny 11794
Grant 5R29AI030492-02 from National Institute Of Allergy And Infectious Diseases IRG: BM
Abstract: Salmonellosis continues to be a major health problem in the United States and the rest of the world. Penetration of intestinal epithelial cells is a common feature of all Salmonella species. Despite the central importance of this event in the pathogenicity of these organisms, little is known about its molecular bases. The broad objective of this study is to understand the molecular mechanisms of Salmonella invasion of non- phagocytic cells and to identify all the biochemical components involved in this interaction. The principal investigator has recently cloned a group of genes (invA, B, C and D) that allow S. typhimurium to penetrate tissue culture cells. The functional study of these genes by a combination of biochemical, tissue culture and genetic techniques will be the main focus of this research. Mutated inv genes will be introduced into wild-type S. typhimurium to determine their specific role in invasion to cultured epithelial cells. The localization of the inv gene products in the bacterial cell as well as their ability to bind to eukaryotic cells will be examined. Fusions to reporter genes will be employed to examine the regulation of expression of the inv genes in response to exposure to tissue culture cells as well as to other environmental influences. The role of DNA supercoiling in this context will be particularly examined using in vivo and in vitro techniques. Mutations that affect expression of the inv genes will be isolated to characterize regulatory loci. Additional pathways of Salmonella invasion to tissue culture cells will be sought by isolating invasion defective mutants and characterizing the mutated loci. The studies proposed will increase the understanding of the molecular bases of Salmonella invasion to non-phagocytic cells. This knowledge will in turn facilitate the developing of new strategies to prevent and treat diseases caused by these and other invasive bacteria.
Keywords: Salmonella infection, Salmonella typhimurium, bacterial DNA, host organism interaction, molecular genetics, Salmonella, Salmonella typhi, antibody, fusion gene, gene expression, gene mutation, genetic mapping, genetic regulation, genetic transcription, genetic translation, nucleic acid structure, reporter gene, Escherichia coli, genetic manipulation, laboratory mouse, laboratory rabbit, microorganism genetics, molecular cloning, nucleic acid sequencing, tissue /cell culture, transfection
Project start date: 1991-01-01
Project end date: 1995-12-31
5R29AI030492-02 (1992): $97177
5R37AI030492-16 (2004): $367240
3R37AI030492-14S1 (2003): $28917
5R37AI030492-15 (2003): $424615
5R37AI030492-13 (2001): $367240
2R37AI030492-12 (2000): $367240
VIRULENCE FACTORS OF SALMONELLA TYPHI
Jorge E Galan, Professor And Chairman
Yale University, 47 College Street, Ste 203, New Haven, Ct 06520-8047
Grant 5R01AI079022-03 from National Institute Of Allergy And Infectious Diseases
Abstract: Salmonella enterica serovar Typhi (S. Typhi), the cause of typhoid fever in humans, continues to be a very significant health problem. It is estimated that there are 16,000,000 cases of typhoid fever every year, resulting in 600,000 deaths. Although most of the cases occur in developing countries, outbreaks occasionally occur in the United States. Unlike other Salmonella enterica serovars, which can infect a variety of hosts, S. Typhi is an exclusive human pathogen. The molecular bases for the host adaptation and unique pathogenicity of these bacteria are poorly understood. However, it is believed that a combination of genome degradation and acquisition of new genetic information has conferred on S. Typhi its unique pathogenic properties. Work in our laboratory has recently focused on a "pathogenicity islet" that is unique to S. Typhi. We have discovered that this region of the chromosome encodes a Cytolethal Distending Toxin, and a Pertussis-like toxin. Remarkably, these toxins are only synthesized when S. Typhi reaches an intracellular location and are exported outside the cell by a unique transport mechanism to be subsequently delivered to target cells by novel paracrine and autocrine pathways. Furthermore, we have found that these toxins share a common unique secretion mechanism for export from the bacterial cytoplasm. In this research project, we intend to characterize this unique toxin delivery pathway and their unique secretion mechanism. We also would like to define their contribution to virulence in the context of S. Typhi pathogenesis and its interaction with host cells. These studies will provide insight into unique and important mechanisms of pathogenicity of S. Typhi, a surprisingly under study but very important human pathogen. Salmonella enterica serovar Typhi (S. typhi), the cause of typhoid fever in humans, continues to be a very significant health problem. It is estimated that there are 16,000,000 cases of typhoid fever every year, resulting in 600,000 deaths. Knowledge gained from this research should help develop novel therapeutic and prevention strategies
Keywords: Antibiotic Agents; Antibiotic Drugs; Antibiotics; Autocrine Systems; Bacteria; Base Sequence; CDT-III; CLD-toxin; CdtB protein; Cell Communication; Cell Cycle Arrest; Cell Interaction; Cell Nucleus; Cell-to-Cell Interaction; Cells; Cessation of life; Chromosomes; Coupled; Cytoplasm; DNA Damage; DNA Injury; Death; Developing Countries; Developing Nations; Development; Disease Outbreaks; Enteric Fever; Event; Extracellular Space; GeneHomolog; Genetic; Genome; Health; Histamine-Sensitizing Factor; Homolog; Homologous Gene; Homologous Protein; Homologue; Human; Human, General; IAP Pertussis Toxin; Intercellular Space; Islet-Activating Protein; Knowledge; Laboratories; Less-Developed Countries; Less-Developed Nations; Location; Lymphocytosis-Promoting Factor; Man (Taxonomy); Man, Modern; Miscellaneous Antibiotic; Molecular; Names; Nucleotide Sequence; Nucleus; Outbreaks; Pathogenesis; Pathogenicity; Pathogenicity Factors; Pathogenicity Islets; Pathway interactions; Pertussigen; Pertussis; Pertussis Toxin; Prevention strategy; Preventive strategy; Production; Property; Property, LOINC Axis 2; Protein Homolog; ProteinHomolog; Proteins; R01 Mechanism; R01 Program; RPG; Research; Research Grants; Research Project Grants; Research Projects; Research Projects, R-Series; Resistance; Role; S. enterica; S. typhi; S. typhosa; S.Typhi; Salmonella enterica; Salmonella enterica serovar Typhi; Salmonella typhi; Salmonella typhosa; Site; Third-World Countries; Third-World Nations; Toxin; Typhoid; Typhoid Fever; Typhoids; Typhus, Abdominal; Under-Developed Countries; Under-Developed Nations; United States; Vacuole; Virulence; Virulence Factors; Whooping Cough; Work; autocrine; base; cytolethal distending toxin; gene product; insight; new therapeutics; next generation therapeutics; novel; novel therapeutics; nucleic acid sequence; paracrine; pathogen; pathogenic bacteria; pathway; public health relevance; resistant; salmonella endotoxin; salmonella toxin; social role
Project start date: 2008-06-01
Project end date: 2013-05-31
Budget start date: 1-JUN-2010
Budget end date: 31-MAY-2011
PFA/PA: PA-07-070
5R01AI079022-03 (2010): $409613
Sponsored Links Excellgen http://Excellgen.com
5R01AI079022-02 (2009): $413750
MOLECULAR MECHANISMS OF SALMONELLA TYPHI PATHOGENICITY
Jorge E Galan, Professor And Chairman
Yale University, 47 College Street, Ste 203, New Haven, Ct 06520-8047
Grant 5R01AI070949-02 from National Institute Of Allergy And Infectious Diseases
Abstract: Program Director/Principal Investigator (Last, First, Middle)GALAN, JORGE E 1 R01 AI 070949 - 01 A2 Salmonella enterica serovar Typhi (S. Typhi), the cause of typhoid fever in humans, continues to be a very significant health problem. lt is estimated that there are 16,000,000 cases of typhoid fever every year, resulting in 600,000 deaths. Unlike other Salmonella enterica serovars, which can infect a variety of hosts, S. Typhi is an exclusive human pathogen. The molecular bases for the host adaptation and unique pathogenicity of these bacteria are not known. However, it is believed that a combination of genome degradation and acquisition of new genetic information has conferred on S. typhiits unique pathogenic properties. The availability of the nucleotide sequence of different S. typhiisolates has provided unique insight into its potential determinants of pathogenicity. Recent work in our laboratory has focused on a "pathogenicity islet" that is unique to S. Typhi. This islet encodes novel toxin that we have named "typhoid toxin". Thisioxin is composed of two active subunits, CdtB, a homolog the active subunit of the Cytolethal Distending Toxin (CDT), and pltA, a homolog of the active subunit of Pertussis toxin. We have found that the expression of this ioxin occurs exclusively when S. Typhi has reached a specific intracellular compartment within host cells. Recent work in our laboratory has also identified a regulatory protein of previously unknown function, STy044g, which specifically controls the intracellular expression of this toxin. We have found that STY044B, which we have named lgeR (for intracellular gene expression regulator), exerts its function as a repressor by binding directly to the toxin promoter. We have also found that constitutive expression of igeR in S. Typhimurium resulted in a drastic reduction in its mouse virulence. We therefore believe that the characterization of the lgeR regulon and its mechanism of action would provide a unique insight into the intracellular biology of this ver/ elusive bacterial pathogen, as well as provide information into the biology of intracellular pathogens in general. lt is therefore the purpose of this project to define the lgeR regulon, to investigate its mode of action and to examine its contribution to virulence using a variety of in-vitro assays and a novel animal model of infection
Keywords: Animal Model; Animal Models and Related Studies; Antibiotic Agents; Antibiotic Drugs; Antibiotics; Bacteria; Base Sequence; Binding; Binding (Molecular Function); Biology; CDT-III; CLD-toxin; CdtB protein; Cells; Cessation of life; Coupled; Death; Developing Countries; Developing Nations; Development; Disease Outbreaks; Enteric Fever; Epithelial Cells; Event; Gene Expression; GeneHomolog; Generalized Growth; Genes; Genetic; Genome; Genomic Islet; Growth; Health; Histamine-Sensitizing Factor; Homolog; Homologous Gene; Homologue; Human; Human, General; IAP Pertussis Toxin; Infection; Islet, Genomic; Islet-Activating Protein; Islets, Pathogenicity; Kinetic; Kinetics; Knowledge; Laboratories; Less-Developed Countries; Less-Developed Nations; Lymphocytosis-Promoting Factor; Lytotoxicity; Mammals, Mice; Man (Taxonomy); Man, Modern; Mice; Miscellaneous Antibiotic; Molecular; Molecular Interaction; Murine; Mus; Names; Nucleotide Sequence; Outbreaks; Pathogenesis; Pathogenicity; Pathogenicity Islets; Pathway interactions; Pertussigen; Pertussis; Pertussis Toxin; Phenotype; Prevention strategy; Preventive strategy; Principal Investigator; Programs (PT); Programs [Publication Type]; Promoter; Promoters (Genetics); Promotor; Promotor (Genetics); Property; Property, LOINC Axis 2; Proteins; R01 Mechanism; R01 Program; RPG; Regulatory Protein; Regulon; Research Grants; Research Project Grants; Research Projects; Research Projects, R-Series; Resistance; Role; S. enterica; S. typhi; S. typhimurium; S. typhosa; S.Typhi; S.typhimurium; Salmonella enterica; Salmonella enterica serovar Typhi; Salmonella typhi; Salmonella typhimurium; Salmonella typhosa; Surface; Third-World Countries; Third-World Nations; Tissue Growth; Toxin; Typhoid; Typhoid Fever; Typhoids; Typhus, Abdominal; Under-Developed Countries; Under-Developed Nations; United States; Virulence; Whooping Cough; Work; base; cytolethal distending toxin; cytotoxicity; gene product; genetic regulatory protein; in vitro Assay; insight; islet; model organism; mutant; new therapeutics; next generation therapeutics; novel; novel therapeutics; nucleic acid sequence; ontogeny; pathogen; pathogenic bacteria; pathway; programs; regulatory gene product; resistant; social role
Project start date: 2009-05-15
Project end date: 2011-04-30
Budget start date: 1-MAY-2010
Budget end date: 30-APR-2011
PFA/PA: PA-07-070
5R01AI070949-02 (2010): $315946
1R01AI070949-01A2 (2009): $315946
MOLECULAR GENETIC ANALYSIS OF SALMONELLA CELL INVASION
Jorge E Galan, Professor And Chairman
Yale University, 47 College Street, Ste 203, New Haven, Ct 06520-8047
Grant 2R01AI030492-22 from National Institute Of Allergy And Infectious Diseases
Abstract: One of the most significant developments in the field of bacterial pathogenesis research in the last few years has been the discovery that many bacterial pathogens have evolved complex specialized machines to transfer multiple bacterially-encoded proteins into eukaryotic cells. One of this type of machines is the type III secretion system (T3SS). A great deal of attention has been devoted to the study of these systems because they are essential virulence determinants for the bacterial pathogens that encode them. Proteins delivered by these machines have the capacity to modulate a variety of cellular functions and are collectively known as "effectors". Through work supported by this Grant, we have been studying a T3SS from Salmonella enterica serovar Typhimurium (S. Typhimurium), encoded within its pathogenicty island 1 (SPI-1). This system mediates several phenotypes that are essential for virulence including bacterial entry into and survival within non-phagocytic cells, the induction of programmed cell death in macrophages, and the stimulation of innate immune responses and inflammation in the intestinal tract. During the previous funding period we have made important discoveries that have significantly advanced our knowledge of this system and T3SSs in general. During the next funding period, we intend to continue this line of investigation, focusing our efforts on less-well understood aspects of T3SSs. More specifically, we propose to use a multidisciplinary approach to 1) To investigate the function of the "export apparatus" of the S. Typhimurium SPI-1 T3SS; 2) To investigate the function of InvA, a core component of the T3SS; 3) To investigate the composition and assembly of the SpaO- organized platform; and 4) To obtain a high resolution in situ view of the S. Typhimurium SPI-1 T3SS. It is hoped that accomplishing these objectives will not only enhance our understanding of Salmonella spp. pathogenesis but also our understanding of T3SSs in general. Since this system is central to the pathogenesis of many important pathogenic bacteria, these studies may provide the bases for the development of broadly applicable anti-infective strategies. Many important bacterial pathogens have evolved the capacity to "inject" proteins using a specialized nano-machine known as the type III secretion system. Bacterial proteins injected by this nanomachine manipulate the cells of the body for the pathogen´s benefit. This Grant intends to better understand how this machine works in the bacterial pathogen Salmonella Typhimurium, which causes inflammatory diarrhea and is one of the most common causes of food poisoning. Since this system is central to the virulence of many important pathogenic bacteria, it is hoped that the understanding of the function of type III secretion systems will provide the bases for the development of broadly applicable anti infective drugs
Keywords: ATP phosphohydrolase; ATPase; Adenosine Triphosphatase; Adenosinetriphosphatase; Anti-Infective Agents; Anti-Infective Drugs; Anti-Infectives; Anti-infective Preparation; AntiInfective Drugs; AntiInfectives; Antiinfective Agents; Apoptosis; Apoptosis Pathway; Applications Grants; Attention; Bacterial Gene Proteins; Bacterial Proteins; Bordetella; Cell Body; Cell Death, Programmed; Cell Function; Cell Process; Cell physiology; Cells; Cellular Function; Cellular Physiology; Cellular Process; Chaperone; Chlamydia; Complex; Cryo-electron Microscopy; Cryoelectron Microscopy; Development; Diarrhea; E coli; Electron Cryomicroscopy; Epithelial Cells; Escherichia coli; Eukaryote; Eukaryotic Cell; Food Poisoning; Funding; Gene Products, Bacterial; Generations; Genetic analyses; Grant; Grant Proposals; Grants, Applications; INFLM; Imagery; Immune response; In Situ; In Vitro; Inflammation; Inflammatory; Intestinal; Intestines; Investigation; Island; Knowledge; Lead; Mass Spectrum; Mass Spectrum Analysis; Mediating; Miyagawanella; Molecular Chaperones; Molecular Genetic; Molecular Genetics; Needles; Organelles; P. aeruginosa; P.aeruginosa; Pathogenesis; Pb element; Phagocytes; Phagocytic Cell; Phenotype; Photometry/Spectrum Analysis, Mass; Protein Secretion; Proteins; Pseudomonas aeruginosa; Pseudomonas pyocyanea; Regulation; Research; Resolution; Role; S. enterica; S. typhimurium; S.typhimurium; Salmonella; Salmonella enterica; Salmonella typhimurium; Shigella; Solutions; Spectrometry, Mass; Spectroscopy, Mass; Spectrum Analyses, Mass; Spectrum Analysis, Mass; Spi-1; Structure; Subcellular Process; System; System, LOINC Axis 4; Type III Secretion System; Type III Secretion System Pathway; Virulence; Visualization; Work; Yersinia; amebocyte; base; bedsonia; bowel; cell body (neuron); communicable disease control agent; cross-link; crosslink; cryoEM; electron tomography; eukaryotida; gel electrophoresis; gene product; genetic analysis; heavy metal Pb; heavy metal lead; host response; immunoresponse; in vivo; insight; interdisciplinary approach; lambda Spi-1; macrophage; nano machine; nanomachine; neural cell body; neuronal cell body; particle; pathogen; pathogenic bacteria; protein complex; public health relevance; secretion process; social role; soma
Relevance: Many important bacterial pathogens have evolved the capacity to "inject" proteins using a specialized nano-machine known as the type III secretion system. Bacterial proteins injected by this nanomachine manipulate the cells of the body for the pathogen´s benefit. This Grant intends to better understand how this machine works in the bacterial pathogen Salmonella Typhimurium, which causes inflammatory diarrhea and is one of the most common causes of food poisoning. Since this system is central to the virulence of many important pathogenic bacteria, it is hoped that the understanding of the function of type III secretion systems will provide the bases for the development of broadly applicable anti infective drugs
Project start date: 1991-01-01
Project end date: 2015-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-07-070
2R01AI030492-22 (2010): $490357
NOVEL SALMONELLA ANTIGEN DELIVERY VECTORS
Jorge E Galan, Professor And Chairman
State University New York Stony Brook Stony Brook, Ny 11794
Grant 5R01AI036520-02 from National Institute Of Allergy And Infectious Diseases IRG: SRC
Abstract: Efficient protection against diseases caused by infectious agents often requires the action of both humoral and cellular immune mechanisms. Therefore, an ideal antigen delivery system should be capable of stimulating all branches of the immune system, in particular if such a delivery vector is to be used to construct polyvalent vaccines. We and others have made use of avirulent strains of Salmonella typhimurium endowed with the ability to express cloned genes from other pathogens to stimulate immune responses against the recombinant virulence antigens. Following oral inoculation, these organisms are known to invade and proliferate in the gut associated lymphoid tissue (GALT) therefore most researchers have focused on the use of avirulent Salmonella vectors to stimulate mucosal immune responses to heterologous antigens. Even though humoral (in particular mucosal) immune responses are an important part of the protective mechanisms against pathogens, it is clear that for efficient protection, cell mediated immunity is often essential. This is particularly so when the pathogen in question is a virus or an intracellular bacterium. In these cases, Class I restricted immune responses are thought to be crucial for protection. During its entire intracellular life cycle in the host, S. typhimurium remains enclosed in an endocytic vesicle. As a consequence of this characteristic, Class I restricted immune responses against heterologous antigens carried by these organisms are generally poor. It is the objective of our proposed research project to construct novel avirulent strains of S. typhimurium capable of stimulating vigorous Class I restricted immune responses in the vaccinated host by altering their intracellular traffic. The effectiveness of this approach will be assessed by testing the ability of the engineered strains to induce Class I restricted immune responses against peptides derived from the Influenza virus Nucleoprotein. The availability of avirulent S. typhimurium strains better suited to stimulate Class I restricted immune responses will significantly aid the development of polyvalent vaccines against viral as well as a variety of very important bacterial pathogens.
Keywords: Salmonella, drug delivery system, drug design /synthesis /production, drug screening /evaluation, MHC class I antigen, cellular immunity, endocytosis, gene expression, gut associated lymphoid tissue, humoral immunity, mucosa, nucleoprotein, oral administration, secretory immune system, Salmonella typhimurium, electron microscopy, laboratory mouse, molecular cloning, plasmid
Project start date: 1994-09-01
Project end date: 1998-05-31
5R01AI036520-02 (1995): $189102
1R01AI036520-01 (1994): $149129
5R01AI036520-04 (1997): $204126
SALMONELLA TYPE 3 SECRETION SYSTEM FOR ANTIGEN DELIVERY
Jorge E Galan, Professor And Chairman
Yale University 47 College Street, Ste 203 New Haven, Ct 065208047
Grant 5R01AI046953-05 from National Institute Of Allergy And Infectious Diseases IRG: ZRG1
Abstract: Avirulent strains of Salmonella typhimurium endowed with the ability to express cloned genes from other pathogens are being widely considered as platforms for the construction of polyvalent vaccines. Although Salmonella typhimurium are excellent carriers to stimulate mucosal and humoral immune responses directed to the heterologous antigens delivered by avirulent vaccine strains, the class I restricted immune responses against these antigens are generally poor. This limitation stems from the fact that Salmonella spp. remain inside the phagocytic vesicle throughout their entire intracellular stage. We have recently developed a system that overcomes this limitation. This system is based on the use the Salmonella type III secretion system to deliver effector bacterial proteins into the cytosol of infected cells. We have adapted this system to deliver heterologous viral epitopes into class I-antigen presenting to stimulate strong class I-restricted immune responses. It is the objective of our proposed research project to further develop the type III secretion-based delivery system into a versatile platform capable of delivery complex antigens to different compartments of the antigen-presenting cellular machinery. More specifically we propose 1) To examine the size and/or structural limitations for the delivery of antigens by the S. typhimurium type III secretion system; 2) To evaluate the ability of the chimeric proteins constructed in specific Aim 1 to induce class I restricted immune responses after delivery by the type III secretion of avirulent vaccine strains of S. typhimurium.; 3) To adapt the S. typhimurium type III secretion system for the delivery of epitopes to the class II antigen presenting pathway; and 4) To evaluate the effect of mutations on S. typhimurium effector signaling proteins (e. g. SopE, SptP, SipA and SopB) on its ability to stimulate class I or class II restricted immune responses in vivo and in vitro. The studies proposed here will expand the use of the S. typhimurium type III secretion system to deliver complex antigens to both the class I and class II antigen presenting pathways. This will significantly broaden the utility of avirulent strains of Salmonella as platforms for the development of polyvalent vaccines.
Keywords: AIDS vaccine, Salmonella typhimurium, antigen presentation, vaccine development, vector vaccine, MHC class II antigen, Orthomyxoviridae, Vesiculovirus, chimeric protein, gene mutation, lymphocytic choriomeningitis virus, simian immunodeficiency virus, viral vaccine, virus antigen, laboratory mouse
Project start date: 2000-02-01
Project end date: 2006-01-31
5R01AI046953-05 (2004): $411764
5R01AI046953-04 (2003): $400780
5R01AI046953-02 (2001): $379760
Sponsored Links Excellgen http://Excellgen.com
1R01AI046953-01 (2000): $385584
PREDOCTORAL TRAINING PROGRAM IN MICROBIAL PATHOGENESIS
Jorge E Galan, Professor And Chairman
Microbial Pathogenesisyale University
47 College Street, Ste 203
new Haven, Ct 065208047
Grant 5T32AI007640-02 from National Institute Of Allergy And Infectious Diseases IRG: MID
Abstract: adapted ) A new interdepartmental program at Yale is described for training in Microbial Pathogenesis. The new Section of Microbial Pathogenesis at Yale has, at present, three faculty Jorge Galan, the Principal Investigator of this training grant who is the Lucille B. Markey Professor of Microbiology and was recruited in 1998, Norma Andrews, who holds a joint appointment in the Department of Cell Biology, and Craig Roy, who came with Dr. Galan from Stony Brook. An increase in this program to seven faculty is expected during the next four years. There are 42 other faculty trainers in the program, drawn from basic science, medical and public health departments with credible common interests in microbial pathogenesis or biology. Training slots for ten graduate students per year are requested. In their first year, trainees will take both courses specialized Microbial Pathogenesis and courses common to students in other programs in BBS such as cell biology and genetics. Rotations through three laboratories are required before choosing a laboratory in which to perform Ph.D. research; the freedom of students to choose rotation laboratories outside the labs included as trainers in Microbial Pathogenesis is extremely important but was not addressed. In the second year, students continue course work, and take a qualifying examination at the end of the year. They continue to be overseen by a thesis committee, and are required to attend and present in the Microbiology Seminar Series, which alternates between outside speakers and in-house presentations of students and postdocs. An annual retreat of Microbiology students and faculty is cited as another opportunity to stimulate scientific exchange
Project start date: 2000-08-01
Project end date: 2005-07-31
5T32AI007640-02 (2001): $157373
1T32AI007640-01 (2000): $151022
5T32AI007640-05 (2004): $177106
5T32AI007640-04 (2003): $173491
Jorge E Galan
Yale University
Project start date: 1995-05-01
Project end date: 2013-04-30
MOLECULAR GENETIC ANALYSIS OF SALMONELLA CELL INVASION
Jorge E Galan, Professor And Chairman
Microbial Pathogenesisyale University
47 College Street, Ste 203
new Haven, Ct 065208047
Grant 5R37AI030492-19 from National Institute Of Allergy And Infectious Diseases IRG: NSS
Keywords: Salmonella, cell, molecular genetics, secretion Salmonella infection, actin, antiinfective agent, apoptosis, bacteria, base, birth, chromosome, computer, cytokine, cytoskeleton, electron microscopy, gene, gene mutation, health, kinetosome, lead, macrophage, protein, transcription factor
Project start date: 1991-01-01
Project end date: 2010-06-30
5R37AI030492-19 (2007): $441009
5R37AI030492-18 (2006): $444007
4R37AI030492-17 (2005): $441450
Sponsored Links Excellgen http://Excellgen.com