Martin Boulanger

Assistant Professor, Biochemistry/Microbiology Department
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Phone: (250) 721-7072
Department Page
Research Area: structural basis of host-parasite interactions

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Research Profile

Structure of host-pathogen interactions the key to new drugs

Dr. Martin Boulanger studies the structural interactions between proteins, such as the interactions between microbial pathogens and their hosts. His specialty has many applications and his projects are wide-ranging. One of his projects involves the protozoan Toxoplasma gondii, which causes the flu-like disease toxoplasmosis.

Although toxoplasmosis is generally mild, it is still an important disease to treat in Canada. It can be fatal to AIDS patients, and it is also a serious concern for pregnant mothers: infected fetuses can have permanent brain damage. In 1995, Victoria’s water supply was contaminated with T. gondii, and more than 100 people, including 12 newborns, were infected.

Boulanger reasons that if he could figure out the three-dimensional structure of the binding site between the human cell and the protozoan, he could design a drug that could block T. gondii from binding and spreading. Boulanger is interested in a group of T. gondii proteins called Surface Antigen Glycoproteins (SAGs), which are, as the name suggests, proteins found on the surface of the protozoan. T. gondii has about 190 different SAGs, and there is a good chance at least some of them help the parasite bind to its host cell. A collaborator, Michael Grigg (National Institutes of Health, Washington, DC), has identified one specific SAG that is likely to be involved in host binding.

Boulanger cloned the gene, purified the SAG protein, and then used X-ray crystallography to give a three-dimensional model of the protein. This is only the second SAG protein for which the structure has been solved.

Working with Dr. Fraser Hof, a fellow CBR member from UVic’s Chemistry Department (link), Boulanger is using computer algorithms to virtually screen (on a structural and chemical basis) known drugs to see if any will bind to his SAG. This new computational technique greatly reduces the need for conventional screening through lab assays that are prohibitively costly.

When Boulanger and Hof get some positive hits with their virtual screen, they will test these molecules to see if they bind to the protozoan. If they find a compound that can bind to the SAG, the collaborators will have a starting point for designing a new drug. By understanding the chemical characteristics and the shape of the binding site, they can chemically tweak the compound to come up with a better fit.

It is important to note that this is a radically new approach to designing antibiotics. Historically, researchers would simply screen compounds to see what would kill microbes, and then find out how it worked later.

Boulanger has had past success in antibiotic design: as a Senior Scientist in Structural Chemistry at Affinium Pharmaceuticals (2004-2006), he helped design a new antibiotic against Staphylococcus infections. This drug (now in clinical trials) is notable because it is effective against methicillin-resistant Staphylococcus aureus (MRSA), referred to as a “superbug” because of its resistance to most current antibiotics.

Boulanger feels it is important for academic institutions, such as the Centre for Biomedical Research, to take on the challenge of designing new antibiotics since most drug companies are ignoring this need in favour of more lucrative drugs.