Project: Research project

Project Details


This training program is designed so that the investigator-candidate can
develop the necessary skills to become an independent physician-
scientist. The program builds on the skills and interests attained in
the previous three years of a post-doctoral training position, during
which the candidate adapted a novel molecular genetic tool for
application in the clinical realm. Specifically, mycobaceriophages,
viruses which infect Mycobacterium spp. including M. tuberculosis, were
designed to express a reporter gene encoding the firefly light-emitting
enzyme luciferase upon infection of a viable mycobacterium. This
technology, which can be used to rapidly detect M. tuberculosis as well
as determine its drug susceptibilities, is much needed to combat the
resurgence of tuberculosis associated with the AIDS epidemic. The
current application aims to investigate the genetic mechanisms
underlying this technology in order to facilitate rational improvements
in the systems's performance, while solidifying the candidates facility
in the techniques of molecular genetics. The specific aims are to
identify phage and host factors which influence the efficiency of the
detection scheme. Specifically, the virus has certain features--its
lytic phenotype and its shutdown of host protein synthesis which are
unfavorable in its adopted role as a producer of receptor genes, yet are
required for its effective propagation as a reagent. Cloning the
determinants of these two processes will allow their rational
regulation. The mycobacterial receptor for phage is an important
parameter for both sensitivity and specificity of phage infection; its
expression should correlate with the spectrum and degree of
infectability of related mycobacteria, some of which are nonpathogens.
Knowledge of receptor regulation will help optimize the conditions for
performing phage infections, and perhaps allow selective detection of
pathogens. The results of this work will produce a superior diagnostic
reagent with an extended range of applications, and will likely provide
valuable information in the biology of mycobacteriophage and
mycobacteria. At the conclusion of the training period, the candidate
investigator will have had extensive exposure to the methods of
microbiology and molecular biology, and the experience to establish an
independent research program in an academic setting, with a close
connection to clinical medicine.
Effective start/end date7/15/986/30/04


  • Infectious Diseases
  • Pulmonary and Respiratory Medicine


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