The "NIH Roadmap for Medical Research" released last week
by NIH Director Elias A. Zerhouni contains several important physical
sciences and interdisciplinary components. The plan will guide NIH's
research during the 21ast century, and has three major themes: New Pathways
to Discovery, Research Teams of the Future, and Re-engineering the Clinical
Research Enterprise. Selections from the first two themes pertinent
to physical sciences research are below. The entire plan may be viewed
at http://nihroadmap.nih.gov
NEW PATHWAYS TO DISCOVERY:
"To fully capitalize on the recent completion of the human genome
sequence and many recent discoveries in molecular and cell biology,
the research community needs wide access to technologies, databases
and other scientific resources that are more sensitive, more robust
and more easily adaptable to researchers' individual needs. Among the
resources to be established are libraries of chemical molecules that
may provide: probes of biological networks; imaging probes for molecular
and cellular events; improved computational infrastructure for biomedical
research; nanotechnology devices capable of viewing and interacting
with basic life processes; and potential targets for new therapies.
"These initiatives will provide a solid scientific foundation
for new strategies for diagnosing, treating, and preventing disease.
Implementation groups in this area are: Building Blocks, Biological
Pathways, and Networks. Molecular Libraries & Molecular Imaging.
Structural Biology. Bioinformatics and Computational Biology. Nanomedicine"
Molecular Libraries and Imaging:
"In these initiatives, NIH will support development of high-specificity/high-sensitivity
probes with the goal of improving detection sensitivity 10- to 100-fold
within five years. An existing NIH database of imaging probes relevant
to cancer and brain function will be expanded to establish a single
database that describes specificities, activities and applications of
imaging probes for a wide range of diseases and biological functions.
"In addition, NIH will construct an Imaging Probe Development
Center to provide a mechanism for producing significant quantities of
probes for which there is no good commercial supplier, as well as to
generate novel imaging probes for biomedical research and clinical applications.
The development of these probes will be aided by discoveries that emerge
from the screening of small molecules for their affinity for targets
of interest. Once developed, these probes will in turn aid the development
of effective therapeutic agents by monitoring their biological behavior.
"Molecular imaging holds great promise for early detection and
treatment of numerous diseases, for providing researchers with detailed
information about cellular physiology and function, and for facilitating
the goal of personalized medicine. By significantly enhancing the support
of this emerging field, the NIH will ensure that molecular imaging will
become a powerful tool for biomedical research and will be a synergistic
component of the overall research in molecular medicine that promises
landmark improvements in clinical care."
Structural Biology:
" The NIH Roadmap's Structural Biology initiative is a strategic
effort to create a gallery of molecular pictures of the shapes of all
the different types of proteins in living things. This research investment
will involve the development of rapid, efficient and dependable methods
to produce protein samples that scientists can use to determine the
three-dimensional structure, or shape, of a protein. The new effort
will catalyze what is currently a hit-or-miss process into a streamlined
routine, helping researchers clarify the role of protein shape in health
and disease.
"What will it take to accomplish this task? NIH will begin by
funding interdisciplinary groups of scientists to develop innovative
methods for producing large quantities of membrane proteins, those proteins
that are wedged tightly within the wrappings of our cells. Scientists
currently find it extremely difficult to wrestle these proteins out
of cells in a condition suitable for structure-mapping techniques.
"Project planners expect that the development of new, protein-producing
methods will lead to the creation of specialized facilities that will
be capable of quickly and efficiently manufacturing large quantities
of research-grade membrane protein samples. Once scientists have access
to sufficient quantities of proteins for their experiments, they can
determine a protein's shape using standard methods involving X-rays
or extremely powerful magnets."
Bioinformatics and Computational Biology:
"Biology has always been a haven for microscopes, test tubes and
Petri dishes, but this conventional picture of the field is expanding
rapidly. Sophisticated techniques borrowed from physics enable scientists
to use computers and robots to separate molecules in solution, read
genetic codes or paint pictures of the three-dimensional shapes of natural
molecules like proteins. All of these techniques generate large amounts
of data, and biology is changing fast into a science of information
management."
"By embarking on the Bioinformatics and Computational Biology
initiatives, the NIH Roadmap is paving a future ‘information superhighway'
dedicated to advancing medical research. A central focus of the initiative
will be a set of National Centers for Biomedical Computing, the first
few of which will be funded next year.
"As the centers begin to generate the software and data management
tools to serve as fundamental building blocks for 21st century medical
research, individual scientists will be funded to work together with
the centers. ‘Big science' and ‘small science' will work hand-in-
hand to advance all of science. Through these efforts, researchers will
be able to share data gathered from large experiments. The best minds
will be able to work together more efficiently to tackle unsolved biomedical
mysteries, such as the role of heredity in individuals' different responses
to medicines and the complex interplay of genetic and environmental
factors in common diseases such as heart disease, cancer and diabetes.
"The Bioinformatics and Computational Biology initiatives also
will create a national software engineering system. Through a computer-based
grid, biologists, chemists, physicists and computer scientists anywhere
in the country will be able to share and analyze data using a common
set of software tools. Developers of the project envision that the system
will resemble that of the integrated software packages for office tools
installed on most home computers today, in which information can be
traded seamlessly between software such as spreadsheets, word processing
and e-mail programs."
Nanomedicine:
"Federally supported research in this area, conducted under the
rubric of the National Nanotechnology Initiative, is ongoing with coordinated
support from several agencies. The NIH Roadmap's Nanomedicine initiatives
will build on these efforts, with its focus centering squarely on health-related
nanotechnology applications."
"NIH will begin its effort by establishing a handful of Nanomedicine
Centers, which will serve as the intellectual and technological centerpiece
of the Nanomedicine initiatives. These centers will be staffed by a
highly interdisciplinary scientific crew including biologists, physicians,
mathematicians, engineers and computer scientists. Research conducted
over the first few years will be spent gathering extensive information
about how molecular machines are built. A key activity during this time
will be the development of a new kind of vocabulary – lexicon –
to define biological parts and processes in engineering terms.
"Once researchers have completely catalogued the interactions
between and within molecules, they can begin to look for patterns and
a higher order of connectedness than is possible to identify with current
experimental methods. Mapping these networks and understanding how they
change over time will be a crucial step toward helping scientists understand
nature's rules of biological design. Understanding these rules will,
in many years' time, enable researchers to use this information to address
biological issues in unhealthy cells. The availability of innovative,
body-friendly nanotools will help scientists figure out how to build
synthetic biological devices, such as miniature, implantable pumps for
drug delivery or tiny sensors to scan for the presence of infectious
agents or metabolic imbalances that could spell trouble for the body."
RESEARCH TEAMS FOR THE FUTURE:
"The scale and complexity of today's biomedical research problems
increasingly demands that scientists move beyond the confines of their
own discipline and explore new organizational models for team science.
For example, imaging research often requires radiologists, physicists,
cell biologists, and computer programmers to work together on integrated
teams. Many scientists will continue to pursue individual research projects;
however, they will be encouraged to make changes in the way they approach
the scientific enterprise. NIH wants to stimulate new ways of combining
skills and disciplines in both the physical and biological sciences.
The Director's Innovator Award will encourage investigators to take
on creative, unexplored avenues of research that carry a relatively
high potential for failure, but also possess a greater chance for truly
groundbreaking discoveries. In addition, novel partnerships, such as
those between the public and private sectors, will be encouraged to
accelerate the movement of scientific discoveries from the bench to
the bedside."
"Biomedical research traditionally has been organized much like
a series of cottage industries, lumping researchers into broad areas
of scientific interest and then grouping them into distinct, departmentally
based specialties. But, as science has advanced over the past decade
and the molecular secrets of life have become more accessible, two fundamental
themes are apparent: the study of human biology and behavior is a wonderfully
dynamic process, and the traditional divisions within biomedical research
may in some instances impede the pace of scientific discovery.
"To lower these artificial organizational barriers and advance
science, this set of NIH Roadmap initiatives will establish a series
of awards that make it easier for scientists to conduct interdisciplinary
research. These new awards include funding for: training of scientists
in interdisciplinary strategies; creation of specialized centers to
help scientists forge new and more advanced disciplines from existing
ones; and initiation of forward-looking conferences to catalyze collaboration
among the life and physical sciences, important areas of research that
historically have had limited interaction.
"Interdisciplinary research integrates the analytical strengths
of two or more often disparate scientific disciplines to solve a given
biological problem. For instance, behavioral scientists, molecular biologists
and mathematicians might combine their research tools, approaches and
technologies to more powerfully solve the puzzles of complex health
problems such as pain and obesity. By engaging seemingly unrelated disciplines,
traditional gaps in terminology, approach and methodology also are gradually
eliminated. With roadblocks to potential collaboration removed, a true
meeting of minds can take place that broadens the scope of investigation
into biomedical problems, yields fresh and possibly unexpected insights,
and may even give birth to new hybrid disciplines that are more analytically
sophisticated.
"By establishing new awards aimed at building interdisciplinary
research teams, NIH hopes to help accelerate research on diseases of
interest to all of its institutes, centers and offices with an eye toward
improving the nation's public health. As currently planned, the first
awards will be made in FY 2004 to establish 15 planning grants for interdisciplinary
research centers. In addition, Request for Applications, or RFAs, will
also be issued in FY 2004 to provide training to scientists in this
emerging area of science.
"In developing these NIH Roadmap initiatives, organizers have
taken great pains to lower several traditional barriers that have slowed
interdisciplinary studies. For instance, the new awards will: grant
principal investigator status to not one investigator, as is now the
norm, but to all key members of the research team; provide indirect
research costs to multiple institutions involved in the research; require
integrated reviews of grants, which take into account the melding of
the various disciplines to the problem at hand; and encourage the interdisciplinary
team to evolve in both directed and serendipitous ways."
Information on grants and funding opportunities can be found at: http://nihroadmap.nih.gov/interdisciplinary/grants.asp
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