OF THE MIND
TECH INSTRUMENT CENTER
TO BLACK MOUNTAIN
MAY UNLOCK MAD COW DISEASE
SPEECH WASN'T FREE
OF THE MIND
You're looking straight down on a cut-away view of a high school. The roof's gone. You focus on several classrooms full of students and a hallway just outside those classrooms, which houses a bank of coin-operated soft drink and snack machines. Somewhere in the shadows of the hall, mysterious figures lurk. Hall monitors.
Now you're in one of the classrooms — chemistry, say — taking a test. Your stomach rumbles, sends you a signal: munchies! Slurpies! You sneak out of the room with a handful of change and visit two or three machines. Yum. But there's a tap on your shoulder, an "ahem," and a hall monitor escorts you back to your room. Bummer. Although you weren't chewing or sipping very loudly, the hallway is quiet again. Stability and order prevail.
To UM Professor Rich Bridges, the "hall monitors" in our little analogy represent glutamate transporter proteins embedded in the membranes of nerve cells, which represent the "classrooms."
Now imagine two variations of this story: First, 75 "students" (glutamate molecules Bridges studies) get signals from their stomachs and converge on the vending machines all at once. (The signals are hunger and thirst; the vending machines represent cell receptors.) The energy in the hall goes through the roof and so does the noise. Alarmingly, the hall monitors are all on a break at the same time, and frenzy leads to chaos. Suddenly, the hall monitors return and leap into action — about 10 of them — and smoothly (if you can believe it) usher almost everyone back across the hall into their classrooms. A few students, chosen at random, are allowed to remain, munching and slurping quietly. Chaos and frenzy subside; stability and order prevail.
All 75 students have stomachs rumbling with hunger and thirst. They
storm into the hall, eager to connect with the food and drink machines — but
watch out! Suddenly 150 hall monitors swoop down on the students and
shove them back into their classrooms, whoosh! The hallway goes still.
Cobwebs develop, and the vending machines go comatose from inactivity.
Systems have stopped. We now have the stability and order of a graveyard.
On the other hand, if the transporters over-regulate the glutamate molecules in the hallway — meaning communication between nerve cells is shut down and the system fails — then the body can fall into a coma. Or develop Alzheimer's disease. Or Lou Gehrig's.
Not much is known about transporters — yet — but much of what is known is because of the work of Rich Bridges and colleagues in pharmacy's Department of Biomedical and Pharmaceutical Sciences, plus faculty in other departments working collaboratively in the Center for Structural and Functional Neuroscience.
In scientific research, as in other disciplines, the discovery process is evolutionary and often indirect. As a researcher, once you understand nerve cells you can move on to signaling molecules, and then to receptors and transporters.
A decade or so ago, doing interdisciplinary post-doctoral work at a medical school in California, Bridges created a drug molecule that looked like glutamate but wasn't. It failed to activate any receptors. Hmmm. Peeking under the hood, Bridges discovered that his molecule made it possible to significantly identify and study glutamate transporters more effectively than had been done before. Indirect discovery, yes, but "bingo!" nonetheless.
Since then, numerous studies and labs around the country have used the first generation of compounds to study transporters, but the UM scientists — both faculty and students — are still pretty much on the cutting edge of basic research in this area. They have developed new compounds to study transporters and are applying new technologies — such as chemistry's John Gerdes with molecular modeling and Sandy Ross with laser spectroscopy.
These things take time, of course, and Bridges says, "We're still making original scratches on the tablet. We're still identifying new proteins, new transporters." Clinical trials for drugs that have yet to be developed are still a few years away. "We're at the most fundamental level," he says.
Why do biomedical research at a university that has no medical school? Well, says Bridges, medical schools don't have physics or chemistry departments or computer science people — but UM does. And the National Institutes of Health agrees that the involvement of many university-based academic departments in transporter research is important. A decade ago grants to the pharmacy school totaled $250,000. Current funding tops $10 million.
from all this, and how? First, the University community. Four years
ago Montana was awarded a grant by NIH to establish the Center for
Biomedical Research and Excellence. It began with six faculty — four
at UM, one at Montana State University-Bozeman and one in Great
Falls at the McLaughlin Research Institute. In the past
A decade ago, the pharmacy school had no doctoral programs. It now offers three, including one in neuroscience that will accept its first students this fall. The school now has 40 graduate students, new courses coming online ("All the research faculty is committed to undergraduate education, as well as graduate," says Bridges) and substantial funding to support undergraduates working summers in all the neuroscience labs.
Then there's the wider Missoula community, which benefits from new drugs and clinical trials at St. Patrick Hospital's two research centers — the International Heart Institute of Montana and the Montana Neuroscience Institute Foundation. Bridges says that while St. Pat's is not a teaching hospital, it nevertheless has the vision to see the importance of research and its potential impact on patients.
Beyond that, there's the national and global community of scientists working at the most basic levels of research — on glutamate transporters, for example — to discover ways of making neuro-communication more efficient. Ultimately, increased efficiency can soften or even partly override the disease processes in the central nervous system that become known as Alzheimer's, ALS, depression or Parkinson's.
Bridges says it's all about balance. We want hungry and thirsty students in the hallway, but not too many at once. We want vending machines doing their job but not burning up. We want hall monitors working as gatekeepers to all the vending machine options, and also working as hallway custodians. If the balance in the central nervous system breaks down, drug therapies can help improve efficiency and restore balance, at least to a degree.
And just how many hall monitors does it take to keep things running well? Good question. UM scientists are on the case.