Students play vital role in laser research
By Julie Neumann
Oct. 9, 2001
On projects ranging from bone surgery to protein identification, students play a vital role in the life
of Vanderbilt’s Free-Electron Laser Center. Undergraduates like Arman Hakimian get an
invaluable introduction to the world of research, while doctoral students like Michelle Baltz-Knorr
hone their research skills and painstakingly construct the intellectual groundwork upon which their
future scientific careers will be based.
The Undergraduate Student
Eyebrow ring, spiky hair, trendy clothes…not exactly your typical nerd attire. Then again twentyyear-old Arman Hakimian is not your typical science geek. He is getting the sort of hands-on
research experience about which most nerds can only dream.
Last summer Hakimian worked on bone ablation with physics research associate Borislav Ivanov.
The research focuses on using the free-electron laser (FEL) to break apart bone by
disassociating its bonds. Not only does the FEL allow a surgeon to cut with extreme precision, but
it also is ideal for the work because it can be tuned to frequencies where most of its energy is
absorbed by the water molecules or proteins that are present in abundance within living bones.
As a result, bone ablation done with the FEL requires less energy than saws or other lasers,
greatly reducing the damage it does to surrounding tissue. [FEL SURGERY]
The opportunity to work at the FEL was a lucky break for Hakimian, who was not expecting to
have such a fascinating summer job. “I wanted to do something different for a change over the
summer,” explained Hakimian. “Every single summer that I was a waiter I told myself that it would
be the last summer. Then the next summer would come and it’d be the easiest thing to make the
most money.” But this spring he took the initiative to ask his physics professor and major advisor
if they knew of any summer positions for undergraduates. “Three days before school was out I
got an e-mail from Professor Haglund1 saying that, if I was still interested, there was a job at the
FEL. I was absolutely ecstatic. I was about to give up, to just be a waiter again.”
When Hakimian showed up for work, it quickly became apparent that the bone ablation research
would be a perfect fit. “I am more interested in something that could be surgically applied since I
hope to be a surgeon one day,” noted the premed physics major. “This is more applicable to what
I enjoy.”
Instead of being put to work as the lab peon, Hakimian got to work on every aspect of the
research. “Borislav and I are the only two that work on this. We are the ones that are hands on
and do everything. We both set up the optics and cut specimens; I personally got the computer
up and running.”
Such responsibility was not always easy. He remembers his first experiences in the lab were like
“pushing me out of a plane with no parachute.” But he is quick to remark “sometimes that is the
best way to learn. You are either interested or not. If you’re not you’ll quit, but if you are you’ll
learn.”
Learning became a daily occurrence for Hakimian. The bone ablation research has required him
to work in areas of physics that were new to him. Though he has never taken an optics class, for
example, he estimates that he has acquired a working knowledge of the subject equivalent to
having completed a semester-long course.
1
Richard F. Haglund, Jr., Professor of Physics and Chair of the Department of Physics and Astronomy
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Students play vital role in laser research
He has also discovered the nature of real-world research. “The first experiments we did were so
rough. I was controlling the read-out on the monitor, pausing it and printing it because we didn’t
have it hooked up to a computer yet. Borislav was manually working the laser shutter, flipping the
thing on and off,” Hakimian recalls, shaking his head with disbelief. “I was very shocked because I
saw so many problems. Everyone told me to calm down; they said ‘This is how it works.’ You take
all the problems and keep going.”
The end result is that Hakimian has come to love the work. “You can take it as a stressful job, but
I think of it as more of a challenge. As long as you are doing all that you can, you’ll come out on
top in the end.”
He hopes to be kept on throughout the remainder of the project. Having been involved since
nearly the beginning, he has watched the research evolve from scratch. He intends to squeeze in
lab time between classes so that he can continue his involvement.
The Doctoral Student
Across the hall from Hakimian, Michelle Baltz-Knorr is in her third year of research at the FEL.
The two labs appear to be mirror images of each other, the standard thick blue pipes of the laser
rising distinctly from a mess of wires and metal. Despite the nearly identical environment,
however, Baltz-Knorr’s work is dramatically different. She devotes her time to running
experiments designed to determine how best to utilize laser light to identify proteins, the
molecular machinery essential to life.
Currently, one of the leading methods for identifying proteins is a technique called matrix-assisted
laser desorption ionization (MALDI)2. It is a form of mass spectrometry3 that utilizes a laser beam
to separate proteins from a matrix and then ionize them so their mass can be measured with a
high level of precision. Mixing proteins with matrix material is a complicated and time-consuming
process. Also, a number of matrix materials are organic acids that can chemically attack protein
molecules; drying the matrix into tiny crystallites also changes the delicate conformation of the
proteins. But the matrix material is necessary because irradiating pure protein samples with highpower lasers breaks up most of the proteins rather than desorbing them. So researchers must
add specific matrix materials to make the method work with the fixed-frequency lasers that they
have available. This creates something of a Catch 22: The scientists want to identify a given
protein, but to do so they must add agents that can alter the very molecules they are attempting
to identify.
Baltz-Knorr hopes to change all that with the help of the FEL. The fact that the FEL beam can be
tuned anywhere from 2 to 10 microns in wavelength greatly expands the universe of possible
matrix materials beyond those that work with conventional lasers. This has allowed the doctoral
student and her colleagues to explore novel matrix materials such as electrophoresis gel and,
most notably, biologically relevant compounds including water. [FEL MALDI]
“If you think about your body and you think about your cells, how much organic acid do you have
in there?” Baltz-Knorr asks wryly. “Hopefully not a lot.” With human cells being made up of nearly
80% water, the ability to perform mass spectrometry directly from water samples should have
dramatic implications for genetics and medical research. “The end product,” she explains, “is to
study proteins directly from cells.”
In addition to water, Baltz-Knorr has also worked with polyacrylamide gel, which is widely used in
gel electrophoresis. By demonstrating that the gel itself can be used as the matrix, she has laid
2
Desorption is the process of removing atoms and molecules that are sticking on a surface. Ionization is the
process of producing electrically charged atoms or molecules.
3 Mass spectrometry is a method for measuring the mass of atoms and molecules with extreme precision. A
sample, usually gaseous, is ionized in a high vacuum and the ions are accelerated into a region containing
strong electromagnetic fields. The fields deflect and focus the ions onto a detector in different locations
depending on the ratio of charge to mass that each carries.
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Students play vital role in laser research
the groundwork for a faster and more cost-effective method for identifying proteins than those
currently in use.
“Having the FEL has allowed us to take more biologically relevant matrices such as
polyacrylamide or water and ask, ‘What wavelength would work? What can we do to not alter the
sample?’” Explains Baltz-Knorr, “Most people have to say, ‘This is the laser I have: What sample
can I use to make it work? What processes do I need to go through?’ With the free-electron laser,
we can ask ‘How should we adjust the laser wavelength and pulse duration to get the optimum
yield of the proteins we are looking for?’ The results are very exciting.”
Three years of research have led to this point. Baltz-Knorr has spent five years at Vanderbilt as a
doctoral student, two of those years under a molecular biophysics training grant funded by the
National Institutes of Health. “I came in as undecided physics but was interested in biological
physics. My advisor, Richard Haglund, encouraged me to apply for the grant, which pulls students
from all disciplines…,” she pauses. “But I had no bio background except for biology and anatomy
in high school.”
So Baltz-Knorr had to start from scratch in biochemistry, spending the summers catching up and
relying on the sympathy of helpful professors. After the first year she was hooked, having
developed a passionate interest in understanding the workings of the body at the molecular level.
Soon after, she was brought into the IR-MALDI group at the FEL in hopes that she could apply
her newfound knowledge.
Immediately the selection and treatment of matrix material caught Baltz-Knorr’s interest. “I started
saying to Richard, ‘Why not look at different matrices, these acids aren’t in your cells, it’s not
natural.’” The team started on glycerol but quickly moved on to explore more biologically relevant
matrices. The FEL’s variable wavelength pushed them in the direction of polyacrylamide and
water.
After several long months of working out kinks in the equipment, Baltz-Knorr was finally able to
put her ideas to the test. “The first time I saw a signal from polyacrylamide gel I just about did
cartwheels around the room. It’s just this feeling of, ‘Oh it worked! Thank God.’”
“[When] you can produce signals that no one else has ever produced before, it’s an incredible
feeling. Especially when you look at it and know that this could have huge applications in the real
world, that people could actually use this in the medical field.”
She has remained passionate ever since. The work has certainly been challenging, but for BaltzKnorr that is part of the fun. “Sometimes what we see is a puzzle… we have to work backwards
and try to find the mechanisms and processes behind what’s happening. Even when you don’t
necessarily understand what you are seeing and why you are seeing it, it’s important. You know it
will help you down the road.”
The mass spectrometry research has been a slow but focused process, much like Baltz-Knorr’s
own growth as a physicist. “When you are starting out, you aren’t sure if this is way you want to
go and you are just trying to find your way, which can be a little daunting. I was very lucky that I
had a great advisor that encouraged me to think up my own project and find something I wanted
to do.”
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