by William Rozycki
bodies seem rather stable: we assume that the billions of cells in our bodies
will, for the most part, stay where they are. But thats not always the
case. In some common mechanisms of disease and of disease resistance, certain
cells move great distances.
Take the spread of cancer, for instance. Cells from a cancer tumor can migrate to other parts of the body, explains Jay X. Tang, assistant professor of physics at IU Bloomington. The larger dynamic in this spread of cancer is metastasis, but the underlying process that allows the cells to migrate is cell motility.
|A phase-contrast image of large granules formed by the protein filaments F-actin. Courtesy photo.|
Tang points out that cell motility
is also connected with positive processes: the bodys white blood cells,
for example, fight disease by moving to attack invasive microorganisms. Yet,
despite the importance of cell motility for both disease and disease resistance,
little is known of the mechanics of individual cell migration or travel.
We do know that motile cells are polarized, Tang explains. That is, they seem to have a front end and a back end, and researchers have noticed that motile cells develop a dense mesh of filaments in the polarity toward which there ismovement. These filaments may be crucial in understanding motility.
The filaments are composed of
a protein called actin, a biomaterial commonly found in muscle cells that
is also a building block for the cytoskeletons of most cells. Tang is studying
actin in its filamentous form, F-actin, as part of his ongoing research into
the assembly and transition phases of filamentous proteins and related polymer
Many proteins share a
common characteristic, Tang says. When put in cationic (positively-charged)
solutions, they draw together in long lines, forming rods. But in different
solutions, proteins can form into a variety of structures, including isotropic
networks, liquid crystalline phases, and densely packed lateral aggregates
that are referred to as bundles. Changes in valency (the balance of electrons
at the atomic level that relates to electrical attraction and repulsion) seem
to trigger the changes in assembly of these proteins. Tang points out that
DNA, which starts out as two long strands of nucleotides, assembles this way
into its distinctive helical shape. Understanding these mechanisms of assembly
and transition has profound implications not only for understanding cell motility,
but also for advancing the fields of biotechnology, materials engineering,
Tang studied physics at Peking
University in China. His introduction to biophysics did not occur until he
came to the United States for graduate studies in 1988. At Brandeis University,
his thesis director happened to be making a study of the phase transitions
of a bacterio-phagea class of long filamentous viruses that infect common
bacteria such as E. coli. One aspect of the study, the effect of a magnetic
field on such filaments, became Tangs dissertation topic and set him
firmly on the path of biophysical research.
A fter graduating from Brandeis with his Ph.D. in 1995, Tang went to work as a research fellow at Harvard Medical School, and in 1997, he became an instructor of medicine there. With his credentials established in the application of physics to biomedical research, Tang was an obvious candidate when the IUB physics department reached an important decision in 1998. Determined to lead in this emerging field, the department decided to fund three faculty positions in biophysics. Tang was hired last year as IUBs first biophysicist.
I spent the fall and winter of last
year getting my laboratory established. It was a lot of work to set it up
from scratch, Tang recalls with a smile.
A tour of Tangs laboratory
shows that the task was considerable. Three shiny new centrifuge machines
are used to prepare and purify samples, which are then stored in a special
super-freezer that maintains a steady temperature at -80°C. A pressure
tank and connecting hose stand ready to feed liquid nitrogen to the freezer
in the case of a power failure. A sophisticated microscope with exchangeable
lenses and filters, a CCD camera hook-up, and an attached computer and monitor
for image capture and analysis allow advanced optical imaging of the protein
assemblies. Petri dishes, sinks, sample-preparation tables, and other equipment,
including a more mundane microscope for simpler imaging tasks, sit in another
section of the lab.
Although he is the only biophysicist
on the Bloomington campus, Tang anticipates the planned hiring of colleagues.
Biophysics has a long history, he says, but it has really
started to flourish in recent years.
Tang sees this flourishing as
a driving force of change in the academic community. Within major universities,
he says, were seeing more applied research, and along with that,
more public support for applied science. Advances in technology improve
the quality of life, he explains, and this in turn drives more research in
Tang points out that this model
has brought changes to the structure of research funding. Nowadays,
he says, the National Institutes for Health give out three times the
amount of funding of the National Science Foundation. But Tang is not
critical of the changing dynamic. Its what the public wants,
he says. Its natural for the public to want applications that
improve our health and quality of life.
Tangs background, so different
from physicists in traditional areas such as particle physics, has helped
him to communicate with a wide range of students, especially in his introductory
physics course for university division students and non-science majors.
My perspective is broader,
he says. It extends beyond physics, and for that reason I think I can
give students an overview that is wider than what is ordinarily expected from
a physics instructor.
Tang is also inaugurating a
course titled Introductory Biophysics,
which is open to graduate students and undergraduates. Im enjoying
teaching it, he says. Its a chance to introduce my own specialty
In his research, Tang and his laboratory team are using microscopic imaging techniques to look in detail at the mechanisms underlying a number of intriguing protein assemblies. A few years ago, Tang discovered that at high concentrations, F-actin self-assembles to form oval, tipped granules called tactoids. His team is now hoping to observe details in the mechanisms that drive that assembly and to learn if such mechanisms are linked to similar granular structures found elsewhere (as in actin patches in yeast and dense bodies in smooth muscle cells).
Much can be understood about
protein assembly by using conventional microscopy. Tang and his laboratory
team use such sophisticated but standard techniques as phase contrast (differentiating
indexes of refraction to make cells more visible), differential interference
contrast (splitting light using prisms), and fluorescence imaging (using a
light source to excite natural or chemically induced fluorescence in target
cell and protein structures).
|Jay X. Tang is assistant professor of phyiscs at Indiana University Bloomington. The Nikon TE-300 is specially equipped with a polarization imaging package for studying biological structures, including living cells. Photo Tyagan Miller.|
But the limits of discovery
can be extended further, Tang believes, by using newly developed optical imaging
techniques and apparatus. Tang has a wish list of imaging equipment he hopes
to obtainat the top of the list are an atomic force microscope (AFM)
and a low background total internal reflection (LBTIR) setup for use with
a high-sensitivity epifluorescence microscope. The request for funding for
the AFM has been a joint effort with David Baxter, an associate professor
of physics whose field is condensed matter physics (see The Era of Spin
Arrives at Swain Hall, page 20). The funding would benefit a number
of laboratories. If funding comes through for the AFM, it will be shared
by all interested research groups in physics, biology, and chemistry,
Equally valuable for imaging
will be the LBTIR, a cutting-edge technology that, in the few laboratories
now using it, has advanced scientific knowledge of cell dynamics by increasing
the visibility of internal cell components. LBTIR allows visualization down
to single macromolecules when there is a suitable fluorescent tag on the target.
Tang does not rely solely on
his own laboratory facilities for imaging. As a fellow of the Indiana
Molecular Biology Institute, located in IUBs Jordan Hall, Tang has
access to its substantial equipment, including an excellent electron microscopy
facility there. Tang and his lab members also have regular research meetings
with the lab staffs of William Saxton and Elizabeth Raff in the IUB biology
department, and Claire Walczak, IUB assistant professor of biochemistry and
Beyond the university, Tang
collaborates with Gerard Wong, a researcher in the X-ray laboratory of Cyrus
Safinya at the University of California, Santa Barbara. In this collaboration,
the two use X-ray imaging to get information about the structure of F-actin
complexes. For another project, a neutron-scattering study of F-actin, Tang
uses the facilities at the Argonne National Laboratory
in Illinois and collaborates with Jyotsana Lal, a staff scientist there.
As Tang establishes his research
program at IU, his sense of excitement helps to offset the many challenges
facing a pioneer in a new area of discovery.
There are constantly new findings in the life sciences, and that produces exciting opportunities, Tang says. Biophysics is by its nature interdisciplinary. Applied physics and instrumentation make a contribution to understanding complex biological systems. I truly consider it a privilege to be part of this great new enterprise.
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