MOLECULAR AND CELLULAR BIOSCIENCES $116,860,000

The FY 2004 Request for the Molecular and Cellular Biosciences (MCB) Subactivity is $116.86 million, an increase of $5.30 million, or 4.8 percent, from the FY 2003 Request of $111.56 million.

Molecular and Cellular Biosciences Funding
(Dollars in Millions)

	FY 2002	FY 2003	FY 2004	Change
	Actual	Request	Request	Amount	Percent
Molecular & Cellular Biosciences Research Projects	112.17	111.56	116.86	5.30	4.8%
Total, Molecular & Cellular Biosciences	$112.17	$111.56	$116.86	$5.30	4.8%

MCB supports research on the fundamental properties and dynamics of the molecular and cellular components of living organisms. This research provides the foundation and framework for understanding multi-scale, complex biological systems and their interactions with the physical world. Study of complex biological questions increasingly requires the tools of genomics, information science, the physical sciences, and mathematics to achieve insights into the mechanisms by which genetic information is transmitted and expressed and the processes by which living cells are organized, communicate, and respond to environmental signals.

Such challenging questions require collaborations of biological scientists with those in the physical sciences, mathematics, computer science, and engineering. MCB is forging partnerships with these disciplines, with the goals of introducing new analytical and conceptual tools to the biological scientist, as well as providing unique training environments for the biologists of the future. This approach is consistent with the overarching goal of
21st Century Biology, which is to understand life at both its most fundamental level and in all its complexity. Exciting progress and integration of advances in genomics, informatics, computer science, mathematics, physics, chemistry, and engineering offer the promise of realizing these ambitious goals.

In FY 2004, core activities in the MCB Subactivity are increased by $5.30 million to enhance support for multidimensional, multidisciplinary, integrative and data-driven 21st Century biological research on the fundamental properties and dynamics of the molecular and cellular components of living organisms. From such knowledge can emerge the innovative ideas and insights that transform our understanding of the natural world, contribute to our economy through new applications in biotechnology, agriculture and the environment, and provide new knowledge that will contribute to our ability to detect and defend against biological threats.

Highlights of areas supported:

Microbial Biology: MCB, through its core activities and through the Microbial Observatories effort, encourages research on microbes at all levels of biological organization. New genome-enabled and biochemical approaches are being used to identify and characterize attributes of microbes, most of which have never before been described. Analysis of microbial genomes is leading to discovery of new organisms and to appreciation of the diversity of their metabolic functions that enable them to occupy diverse habitats and to interact in complex communities. These efforts are consistent with priorities of the interagency effort, "The Microbe Project."

Little is known about wetland bacteria that turn organic matter into the greenhouse gas methane. Now, for the first time, scientists are collecting methane-generating bacteria (called methanogens) from oxygen-poor wetlands, and bringing them to a lab alive. No one has ever cultured and grown methanogens from acidic wetlands in a lab. If the researchers succeed in duplicating the carbon-rich, anaerobic, acidic conditions where methanogens thrive, the organisms may have a future in bioengineering - perhaps in bioremediation of contaminated sites or in the controlled production of methane.

"2010 Project:" Unsolicited research initially funded in MCB led to the discovery of the value of Arabidopsis thaliana as a model flowering plant. The MCB Subactivity will continue to support research enabled by the availability of the complete genome sequence of Arabidopsis to determine the functions of all the genes of this model flowering plant by the year 2010.

Natural nanomachines: MCB core activities support research on the structure, mechanisms of action, and control of the molecules that represent the machinery of the living cell. These natural nanomachines provide models and paradigms for science and technology at the nanoscale.

Capitalizing on the potential of nanotechnology, researchers proposed a new method for rapidly sequencing DNA or RNA. They hypothesized that if single-stranded DNA or RNA could be drawn through a nano-pore in a membrane then changes in the ionic current of the membrane would reflect the properties of the DNA (length, nucleotide composition, etc.). A MCB Small Grants for Exploratory Research award allowed the researchers to successfully test their hypothesis. This method has fewer steps than currently used methods and depends on rapid, molecular events. This can reduce the time and cost of DNA/RNA sequencing by several orders of magnitude. This is being heralded as an extraordinarily important advance. Several publications and patents have resulted and the technology is being tested for commercial application.

Living Networks: Theoretical, computational, and mathematical modeling approaches are playing increasingly critical roles in all areas of the molecular and cellular biosciences - in formulating and testing physical and mathematical models of the structure and function of complex molecules and cellular processes; in analysis of genome data; and in addressing one of the greatest computational challenges facing 21st Century Biology, creating multi-scale models that can integrate our understanding of biological structure, function, and interactions at all levels into a predictive whole.