This application is for the second competing renewal of our interdisciplinary pre-doctoral training grant on The Molecular Pathogenesis of Infectious Diseases at the University of Colorado School of Medicine. This emerging area of investigation encompasses molecular biological and biochemical studies on microbial virulence determinants, host resistance mechanisms, regulation of transcription and translation during infection, structure-function analysis of microbial and host cell molecules that play key roles in infections, analysis of interactions of bacteria and viruses with differentiated host cells in vitro, and studis on bacterial and viral infections in animal models using either wild-type or genetically modified strains of microbes and host animals. The highly interactive members of our training faculty have proven productivity for innovative research in these areas, have secured research funding from NIH, NSF, DOD and other granting agencies, and accumulate years of experience in training pre-doctoral students in the multidisciplinary approaches needed for cutting-edge research on the pathogenesis of infectious diseases. In addition to performing their mentored research projects, our trainees will participate in a comprehensive program of didactic courses, seminars, journal clubs, and research-in-progress meetings that will train them to identify important new research questions, design well-controlled experiments using a wide variety of molecular, cellular and in vivo techniques, critically evaluate and present their results, and understand and apply principles of ethics to their research. Students are selected for appointment to this training program only after they have completed their required course work, passed their preliminary and comprehensive examinations and begun their dissertation research. The breadth of our integrated, interdepartmental training grant will prepare students for successful careers in academia and biotechnology. This dynamic training grant has been remarkably successful. It has fostered new research collaborations and grants among the training grant faculty, improved the curriculum, and fostered interdisciplinary interactions among the pre-doctoral trainees and trainers. In the five years since our training program on the Molecular Pathogenesis of Infectious Diseases was renewed in 2007, our training faculty increased from 21 to 24, and over 30 pre-doctoral trainees have populated at any given time the labs of training grant faculty for the past 8 years. In addition, the number of publications authored by our trainees grew from 29 in the 2002-2006 year period to 62 since 2007. We request four positions each year for the next five years to maintain the level of outstanding interdisciplinary training that our students receive in the multiple aspects of molecular pathogenesis of infectious diseases that are investigated in the laboratories of our training grant faculty.

Public Health Relevance

Bacteria and viruses are major causes of death, disability, and social and economic disruption for millions of people each year. The goals of this training grant are to 1) educate PhD students to investigate the fundamental mechanisms by which microbes infect vertebrate hosts and cause disease, and 2) prepare our graduates for future opportunities in scientific discovery and leadership positions. The training supported by this T32 will further the understanding of human pathogens, thereby contributing to novel ways to diagnose, prevent, treat and cure current and emerging infectious diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Institutional National Research Service Award (T32)
Project #
2T32AI052066-11A1
Application #
8551272
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Robbins, Christiane M
Project Start
2002-08-01
Project End
2018-05-31
Budget Start
2013-06-04
Budget End
2014-05-31
Support Year
11
Fiscal Year
2013
Total Cost
$122,608
Indirect Cost
$8,714
Name
University of Colorado Denver
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Fitzsimmons, Liam F; Liu, Lin; Kim, Ju-Sim et al. (2018) Salmonella Reprograms Nucleotide Metabolism in Its Adaptation to Nitrosative Stress. MBio 9:
Vázquez-Torres, Andrés (2018) Less Is Best in the Convergent Evolution of Typhoidal Salmonella. Cell Host Microbe 23:151-153
Crisler, William J; Lenz, Laurel L (2018) Crosstalk between type I and II interferons in regulation of myeloid cell responses during bacterial infection. Curr Opin Immunol 54:35-41
Shaw, Jeff A; Henard, Calvin A; Liu, Lin et al. (2018) Salmonella enterica serovar Typhimurium has three transketolase enzymes contributing to the pentose phosphate pathway. J Biol Chem 293:11271-11282
Tapscott, Timothy; Kim, Ju-Sim; Crawford, Matthew A et al. (2018) Guanosine tetraphosphate relieves the negative regulation of Salmonella pathogenicity island-2 gene transcription exerted by the AT-rich ssrA discriminator region. Sci Rep 8:9465
Westrich, Joseph A; Warren, Cody J; Klausner, Michael J et al. (2018) Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-Dependent Protein Degradation. J Virol 92:
Kuss-Duerkop, Sharon K; Westrich, Joseph A; Pyeon, Dohun (2018) DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis. Viruses 10:
Kim, Ju-Sim; Liu, Lin; Fitzsimmons, Liam F et al. (2018) DksA-DnaJ redox interactions provide a signal for the activation of bacterial RNA polymerase. Proc Natl Acad Sci U S A 115:E11780-E11789
Reichlen, Matthew J; Leistikow, Rachel L; Scobey, Micah S et al. (2017) Anaerobic Mycobacterium tuberculosis Cell Death Stems from Intracellular Acidification Mitigated by the DosR Regulon. J Bacteriol 199:
Hawman, David W; Carpentier, Kathryn S; Fox, Julie M et al. (2017) MUTATIONS IN THE E2 GLYCOPROTEIN AND THE 3' UNTRANSLATED REGION ENHANCE CHIKUNGUNYA VIRUS VIRULENCE IN MICE. J Virol :

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