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Martha H. Mulks, Ph.D.
Professor
Department of Microbiology and Molecular Genetics
B.A.,
1971, Cornell University
PhD, 1977, Rensselaer Polytechnic Institute
Post-doctoral Studies: 1977-1980, Tufts University School of Medicine and New England Medical Center Hospital
Address:
Department of Microbiology and Molecular Genetics
5193 Biomedical Physical Sciences
Michigan State University
East Lansing, MI 48824
Email: mulks@msu.edu
Telephone: (517) 355-6463 X1574 |
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Research
Research
in my laboratory is focused on the study of bacterial
pathogenesis: how bacteria cause disease in humans and
animals. At this time, the major focus of our research
is Actinobacillus pleuropneumoniae (APP), the causative
agent of porcine pleuropneumonia, a severe and often
fatal respiratory disease of swine. This organism is
of interest to us for two reasons: it is a pathogen
of significant economic importance in the United States
and worldwide, and development of improved vaccines
and diagnostic tools would be of benefit to the swine
industry; and it is an excellent model for the study
of the pathogenesis of pneumonia caused by similar organisms
in humans and other animals of veterinary importance.
A major goal of our research on APP is to identify genes
encoding proteins involved in pathogenesis, either as
virulence factors, regulatory molecules, or components
of pathways necessary for survival in the host animal.
We have developed a genetic system, termed an in vivo expression technology (IVET) system, that allows us
to identify APP genes that are specifically turned on
in the host animal during infection and are turned off
in vitro on standard laboratory media. Using this IVET
system, we have identified over 50 such genes, and are
currently studying the role of these genes in the disease
process. An example of one of these in vivo induced
(ivi) genes is ohr, which encodes an organohydroperoxide reductase
that we postulate may help APP survive oxidative stress
produced by neutrophils in the infected lung. We hope
that this research will be broadly applicable to understanding
the pathogenesis of respiratory diseases in other animals
of veterinary importance as well as in humans, and to the development of improved vaccines and treatments.
As part of this research, we have analyzed the response of these ivi genes to a variety of environmental conditions, such as heat shock, oxidative stress, and limitation of key nutrients. We found that 25% of the APP ivi genes were upregulated in response to limitation of the branched chain amino acids (BCAA) leucine, isoleucine, and valine, and that at least some of these genes were regulated by Lrp (leucine-responsive regulatory protein). This research is leading us in new directions examining the effect of BCAA limitation on virulence gene expression in A. pleuropneumoniae and other respiratory pathogens.
In addition to our work on APP, my lab is also a part of the team of laboratories studying the genetics of host specificity, using the pathogen Burkholderia cenocepacia as our model organism.
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