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2004
WELCOME
FROM VICE PRESIDENT DAN DWYER
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A ROUNDUP OF UM SCIENCE NEWS
PHARMACY
SCHOOL
ON THE GROW
SCHOOL
OF THE MIND
BRAIN STUDIES MAY COMBAT CENTRAL NERVOUS SYSTEM DISEASES
PATHWAYS
OF LIFE
NEW LAB TACKLES VASCULAR DISEASE
GENETIC
HEALING
BIOLOGIST SEEKS DNA-LEVEL CURES FOR HEARING LOSS, CANCER PAIN
HIGH
TECH INSTRUMENT CENTER
SUPER COMPUTING AIDS UM RESEARCH
RETURN
TO BLACK MOUNTAIN
LESS THAN A YEAR AFTER FIRE, NATURE THRIVES
EXTREME
LIVING
HOT POOL CREATURES MAY OFFER GLIMPSE OF LIFE BEYOND EARTH
TUNNELS
TO SAFETY
ANIMALS USE CULVERTS TO CROSS HIGHWAYS
VIENNA
EXPERIENCE
STUDY-ABROAD PROGRAM LEAVES A LASTING IMPRESSION
PROTEINS
MAY UNLOCK MAD COW DISEASE
UM RESEARCHER MICHELE MCGUIRL WORKS TO PROTECT FOOD SUPPLIES
WHEN
SPEECH WASN'T FREE
PROFESSORS DELVE INTO MONTANA'S TROUBLED PAST
FAMILY
ALCHEMY
RESEARCHERS BALANCE SCIENCE, MARRIAGE AND KIDS
CULTURE
CLASH
DIFFERENCES IMPACT ACADEMIC SUCCESS
INVISIBLE
SPACE RAIN
RESEARCHER STUDIES MYSTERIOUS COSMIC RAYS
BRAIN
PAIN
RESEARCHER OFFERS TIPS FOR MIGRAINE SUFFERERS
CAMAS
MAGAZINE
VOICES RISING IN THE WEST
SCHOOL
OF THE MIND
Brain studies
may combat central nervous system disease
By RICHARD
CHAPMAN
Photography by TODD GOODRICH and STEVE KRUTEK
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| A glutamate molecule found in the brain |
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.
Second variation:
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.
This leads us to the heart of our story, which is hall monitors and
the UM scientists who study them in a pharmacy school research center
headed by Bridges. Which vending machines do the students go to, and
anyway, how many students can the hallway tolerate at the same time?
That's the job of the transporters. Glutamate molecules in the hallway
are sending chemical signals that are stimulatory (as opposed to inhibitory).
Unregulated by transporters (no hall monitors), these excitatory signaling
molecules (hungry students) can lead to seizures (frenzy and chaos in
the hallway, clogged vending machines), which cause irreparable harm.
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.
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| UM scientist Rich Bridges (front) confers with lab tech Fred Rhoderick. |
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.
Who benefits
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
two years this faculty has grown to 19.
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.