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.