CONTACT: JENNIFER CRONIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-5661; fax (319) 335-9917
UI researcher receives $6.3 million NIH grant to study hemoglobin
IOWA CITY, Iowa -- A University of Iowa researcher is leading a $6.3
million investigation into how hemoglobin functions at the atomic level
and hopes the study's findings lead to a better understanding of how mutated
forms of the molecule cause certain conditions.
"This basic research should result in new insights into the way
in which hemoglobin transports oxygen throughout the body," said Arthur
Arnone, Ph.D., UI professor of biochemistry. "It also may provide
for better understanding and treatment of diseases involving hemoglobin
and for the design of improved blood substitutes."
Arnone is the principal investigator for the five-year, six-institution
study that began in January. The National Institute of General Medical
Science, a sub-unit of the National Institutes of Health, is funding the
project that, including direct and indirect costs, totals $6.3 million.
Every red blood cell contains 300 million molecules of hemoglobin. Hemoglobin
is a blood protein that binds oxygen in the lungs then delivers the oxygen
to all the tissues in the body. Considered a very efficient oxygen transporter,
each hemoglobin molecule contains four oxygen-binding sites. Once the first
molecules of oxygen bind to hemoglobin, the subsequent molecules bind much
more readily. The same efficiency occurs in reverse when the hemoglobin
releases the oxygen into tissues.
However, one in every 300 individuals has a naturally occurring hemoglobin
mutation. Although most mutations do not affect how the molecules work,
some -- such as the mutation that causes sickle cell anemia -- can be very
serious. By understanding the basic mechanism by which normal hemoglobin
transports oxygen, researchers can better understand the dysfunctions that
result from mutations, Arnone said.
Arnone and other researchers in his laboratory are using X-ray crystallography
(a form of high-resolution microscopy) to see individual molecules of hemoglobin.
Using this technology, the research team will determine the atomic structures
of a large number of hemoglobin mutations that will be made in the lab
by a technique called site-directed mutagenesis.
Researchers at the collaborating institutions will use various complementary
technologies to determine how these mutations alter the hemoglobin's oxygen-binding
efficiency. The other sites involved include labs at Northwestern University,
the University of Pennsylvania, the State University of New York - Buffalo,
Albert Einstein College of Medicine in New York City and the University
of Parma in Italy.