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In this section:
» Studying Protein Structures
Illuminates Functions
» Modeling the Spread of Infectious
Diseases
» Revealing Genetic Influence
on Response to Medicines
» Laying the Foundation for
Stem Cell Research
The vast majority of NIGMS grants support investigator-initiated
studies in basic biomedical fields. These grants yield a wealth
of new knowledge that forms the foundation for medical advances.
The Institute also develops initiatives to catalyze research and
new directions in areas of special interest or opportunity. Recent
developments in several of these initiatives are described below.
Studying Protein Structures
Illuminates Functions
Knowing the structures of proteins helps us understand the critical
roles they play in health and disease and also points the way to
designing new medicines. Protein structure determination is getting
faster and cheaper thanks to a major NIGMS program called the Protein
Structure Initiative (PSI). During the first 5 years of the PSI,
nine pilot centers developed new tools and methods that enabled
them to find the three-dimensional shapes of more than 1,300 proteins.
Ten new PSI research centers funded in FY 2005 plan to produce
three times as many structures in the next 5 years. Four of the
centers will use methods developed during the pilot period to rapidly
determine the structures of proteins found in organisms ranging
from bacteria to humans. Based on this information, scientists will
be able to use computers to quickly and easily model the structures
of a much larger number of proteins. An additional six smaller,
more specialized centers will develop new methods for efficiently
determining the structures of certain types of proteins that are
particularly challenging to study.
As in the pilot phase, the newly funded PSI centers will submit
their structures and related findings to the Protein Data Bank (http://www.rcsb.org/pdb/),
a public repository of three-dimensional biological structure data
that is supported by the National Science Foundation and NIH. From
this repository, researchers can access an abundance of PSI-generated
information that may help them better understand the function of
proteins, predict the shapes of unknown proteins, identify new targets
for drug development, and compare protein structures from normal
and diseased tissues.
In FY 2006, the PSI will establish other resources for the scientific
community. These include a centralized PSI Knowledgebase that will
promote information integration, standardization, and dissemination
and a PSI Materials Repository that will store and distribute resources
generated by the PSI centers.
A key tool for protein structure determination is X-ray crystallography,
which relies on X-ray beamlines at large, national facilities called
synchrotrons. NIGMS, the National Cancer Institute, and the U.S.
Department of Energy have collaborated since 2001 to build three
innovative new X-ray beamlines at Argonne National Laboratory’s
Advanced Photon Source. The research community will have access
to one of the beamlines in FY 2006, and all three will be fully
operational in FY 2007.
PSI scientists have also made advances in nuclear magnetic resonance
(NMR) spectroscopy, the other major tool for capturing data on protein
structures. In FY 2005, Thomas A. Szyperski, Ph.D., of the University
of Buffalo in New York developed a method that allowed his team
to use NMR to solve eight protein structures in less than 20 days.
This is in stark contrast to the time needed to solve just one structure
using traditional NMR techniques, which can take up to a year.
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Modeling the Spread of Infectious
Diseases
The MIDAS program develops computer modeling techniques to analyze,
predict, and respond to infectious disease outbreaks, whether they
occur naturally or deliberately. This interdisciplinary network
of scientists is modeling avian flu in an effort to understand how
an outbreak in humans could spread and to identify effective strategies
for containing the outbreak at its source.
As described in the science advances section, the researchers simulated
outbreaks in Southeast Asia and have more recently turned their
attention to developing models for the United States. Policymakers
throughout the world are using information from MIDAS models in
formulating plans to prepare for potential pandemic flu outbreaks.
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Revealing Genetic Influence
on Response to Medicines
The second phase of the NIH Pharmacogenetics Research Network began
in FY 2005. This program, which NIGMS leads and eight other NIH
components also fund, focuses on how a person’s genes affect
his or her response to medicines. This will maximize the benefits
of treatment while minimizing adverse side effects, ultimately improving
patient outcomes and reducing health care costs. During the first
5 years of the program, the research groups made critical advances
in understanding the interactions between certain genes and drugs
used to treat cancer, heart disease, asthma, and other diseases.
The story of discovery highlights several of the most significant
accomplishments of network scientists.
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Laying the Foundation for
Stem Cell Research
Although human embryonic stem cells hold great promise as a model
system for research and for treating diseases, they pose several
challenges: They are difficult to grow in the lab and scientists
do not yet know how to reliably maintain them in their multipotential
state or direct them to become a specific cell type.
To better understand the basic biology of human embryonic stem
cells and establish the infrastructure needed to work with them,
NIGMS funded three new Exploratory Centers for Human Embryonic Stem
Cell Research in FY 2005. Each center will establish a core facility
to support and train scientists, define optimal growth conditions
and molecular characteristics for maintaining human embryonic stem
cells, and support pilot projects to address some of the most fundamental
questions regarding stem cell biology. The centers join three others
that the Institute funded in FY 2003.
When the exploratory center grants expire, NIGMS is making plans
to replace them with program project grants beginning in FY 2007.
Each of these larger grants would include a core facility and at
least three research projects addressing a basic question in human
embryonic stem cell biology or chemistry relevant to the NIGMS mission.
In addition to advancing scientists’ ability to work with
human embryonic stem cells, the grants would facilitate the use
of the cells as an experimental model system.
Responding to the need for more skilled stem cell researchers who
can advance the field, NIGMS led a group of NIH institutes in developing
a new, ongoing program of fellowships in human embryonic stem cell
research. The program was announced in FY 2005, and the first grants
will be awarded in FY 2006.
The source of the stem cells for all NIGMS activities is limited
to Federally approved stem cell lines listed on the NIH Human Embryonic
Stem Cell Registry.
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