Dr. Marty Boulanger
Research of Martin J. Boulanger
PhD University of British Columbia
The diverse research themes in my lab share the common
experimental approaches of X-ray crystallography,
isothermal titration calorimetry (ITC) and enzyme
kinetics. To support the detailed level of
characterization afforded by these techniques, we utilize
both E. coli and the Baculovirus based protein expression
systems, the latter of which enables us to effectively
target proteins from eukaryotic organisms.
Host/pathogen Interactions
Currently, we are characterizing the molecular
interactions that enable the eukaryotic protozoan
parasite Toxoplasma gondii to attach to, and ultimately
invade virtually every nucleated cell. The protozoan
parasite Toxoplasma gondii is a serious global pathogen
that infects nearly one third of the adult human
population. T. gondii infections can be lethal to a
developing fetus, immunocompromised cancer, AIDS and
organ transplant patients, and can cause severe ocular
infections in both children and adults. T. gondii
infections are also of considerable economic importance
to the agricultural industry, where it causes premature
abortion in a wide range of animals destined for human
consumption. Our goal is to characterize the structural
basis of how key members of a superfamily of
developmentally expressed surface proteins on T. gondii
(known as the SRS adhesins/antigens) mediate parasite
attachment to host cells. Based on this work, we will be
strategically poised to develop therapeutic interventions
to limit infectivity of this widespread zoonotic
pathogen.
Structure Based Drug Design
My lab is also currently involved in several
collaborations with cancer biologists and medicinal
chemists to identify and develop small molecule
inhibitors for a variety of protein based cancer targets.
Our primary focus is aimed at identifying novel drug
candidates that target the recently uncovered molecular
target psoriasin (S100A7). So named because of its
original discovery in abnormally differentiating cells in
psoriasis lesions, psoriasin is particularly prominent in
preinvasive carcinoma in situ in breast, where it is one
of the most highly expressed genes.
Structural Paradigms in Bioremediation
Microbial species have evolved the metabolic
capabilities to degrade a variety of naturally occurring,
thermostable aromatic compounds derived from plants. Man
made aromatic pollutants, however, pose major challenges
for bacterial degradation due to their chemical
complexity, decreased bioavailability and increased
thermostability. As a result, xenobiotic compounds, many
of which are derived from pesticides, paints solvents and
the processing of fossil fuels persist in the environment
and cause irreversible damage to the biosphere. A
promising strategy to catalyze the removal of these
contaminants from the environment is to manipulate
bacterial metabolic pathways to broaden substrate
specificity. As a prerequisite step to the rational
engineering of these biological systems, detailed
descriptions of the enzymes involved are essential. In
this aspect of my research we are focused on
characterizing the novel enzymes that comprise the
recently discovered Benzoate oxidation (Box) pathway in
Burkholderia xenovorans LB400. Experimental efforts are
directed at providing a detailed structural and
biophysical blueprint of each enzyme in the pathway, on
identifying the molecular determinants that govern
substrate specificity and on characterizing the basis for
the cross talk between enzymes during degradation of
benzoate. The long-term objectives of this research are
to better understand the bacterial degradation of
aromatic compounds and to design more efficient
strategies for the bioremediation of environmental
pollutants.