Posted on May 30: Eric Brown battles super bugs one microbe at a time
[img_inline align=”right” src=”http://padnws01.mcmaster.ca/images/eric-brown.jpg” caption=”Eric Brown”]It's a new age in drug discovery. So says professor of biochemistry Eric Brown, who is among a new breed of researchers straddling the borders of microbiology, genetics and chemistry to develop new therapies intended to counter the growing threat of bacterial drug resistance to existing antibiotics.
Using the tools of molecular genetics and enzyme science, Brown and his fellow scientists in McMaster's Antimicrobial Research Centre (ARC) are going after new pathogens by picking genetic targets in infection-causing bacteria and building drugs one protein at a time to disable them. “What's needed now are targets and small molecules that block the function of those targets,” says Brown, who holds a Canada Research Chair in Microbial Biochemistry.
A Flamborough native, he came back to Hamilton in 1998 after several years working in antibacterial drug discovery at a pharmaceutical company in Boston. Although he was arguably closer to the front lines there, he wanted to pursue ideas through a research program of his own.
Today he's studying new bacterial targets along with fellow ARC biochemists Gerry Wright, John Brennan, Justin Nodwell and Paul Berti. Much of their work is taking place in a near-pristine, fourth-floor lab set up late last year in McMaster's Health Sciences Centre, where they collaborate with researchers at area hospitals and further afield as members of the Ontario Genomics Institute.
The lab, called the McMaster High Throughput Screening Laboratory (MAC-HTS), is designed to help in screening thousands of chemical compounds for potential therapeutic use. The only one of its kind in Canada, MAC-HTS was outfitted with funding from the Ontario Research and Development Challenge Fund and additional fund from the University and the private sector.
A quick tour of the lab reveals a bewildering array of equipment, from conventional flasks and petri dishes to computers and a bench-top robotic handling system.
The new lab puts McMaster “ahead of the curve” in screening small molecules and functional genomics for potential use against disease-causing microbes, according to Brown, director of MAC-HTS. “It's the envy of a lot of biotech companies in places like Boston. What we're running is as good as anything at any university in the United States right now.”
At the same time, and like other researchers in the field, the McMaster team is scrambling to keep up with the extraordinary resilience of strains of disease-causing bacteria. The past 20 years have seen a decline in the introduction of new antibacterial agents even as bacterial resistance grows to existing antibiotics. Drug resistance is a mounting health threat that can cause infection and even death especially for people in hospitals and nursing homes whose immune systems are often weaker or even malfunctioning.
Looking for novel drug targets, Brown is pursuing two related research routes.
In one project, he's studying teichoic acids found on the surface of certain pathogenic bacteria. Until recently, researchers dismissed these substances but Brown's work suggests that they're essential in the daily lives of bacteria. He's studying how those enzymes work and how they might be disabled.
In a second project that sees him playing DNA detective, he's studying large stretches of genetic material that enable bacteria to make so-called “mystery proteins.” Despite the explosion of information about microbial genomic sequences, Brown says, we still know little about many proteins made by those stretches of DNA.
“The Holy Grail for antibacterial research is to understand bacterial physiology and the molecular details of protein function.”
Brown studied biochemistry at the University of Guelph, including graduate studies of an enzyme important in milk clotting. That first taste of enzyme science and the reductionist approach to understanding how proteins work was fascinating for Brown. (Guelph and its agricultural roots also made sense for family reasons: his grandparents met there as students in agriculture and home economics, and his brother studied microbiology.)
He moved closer to medicine with his post-doctoral work on medically important proteins at Harvard. “I bought into the idea that I would do fundamental research on projects of high relevance to some medical problem.”
He wasn't the only one connecting biochemistry, molecular biology and medicine. By the late 1980s and early 1990s, physicians were exploring remedies for the problem of infection during organ replacements, for example, and biotech companies were increasingly interested in the uses of biochemistry for drug discovery.
Referring to the convergence of different fields represented by his own research and by the new screening facility, Brown says, “Science these days is all about what's going on around the edges.” He believes biochemistry, in particular, will allow medicine to “uncover the molecular details of a target and provide more opportunity to be intelligent about building drugs” to combat the new generation of super bugs.
