MOLECULAR AND CELLULAR BIOSCIENCES $111,556,000

The FY 2003 Budget Request for the Molecular and Cellular Biosciences (MCB) Subactivity is $111.56 million, a decrease of $3.04 million, or 2.7 percent, from the FY 2002 Current Plan of $114.60 million.

(Millions of Dollars)

All biological processes, taking place at the molecular through ecosystem levels, contribute to the overall imprint of life on this planet. It is the objective of MCB to promote fundamental understanding of the ground rules of molecular and cellular interactions and dynamics. These ground rules provide the framework for understanding multi-scale, complex biological systems and their interactions with the physical world. This is accomplished by supporting innovative and transformative research on complex biological systems, from the individual biomolecule to the cell across a wide range of organisms. Such complex biological questions require the tools of genomics, information science, and mathematics to achieve insights into the molecular mechanisms by which genetic information is expressed and the processes by which living cells are organized, communicate, and respond to environmental signals. Such challenging questions increasingly require collaborations of biological scientists with those in the physical sciences, mathematics, computer science, and engineering. MCB is purposefully 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.

In FY 2003, activities in the MCB Subactivity are decreased by $3.04 million. This reflects the restructuring of the BIO budget to establish the new Emerging Frontiers Subactivity, which was established as an incubator for evolving multidisciplinary research and networking activities. Within the budget request, MCB will include enhanced support for:

• Genome-Enabled Science: The availability of the genome sequences of organisms has enabled new approaches to the study of biology, broadly referred to as "functional genomics" and "genome-enabled science." Examples include analysis of microbial genomes to discover new organisms, determine their genetic capabilities, and study the diversity of metabolic functions that enable them to occupy diverse habitats. Genome-enabled research also seeks to answer questions such as which sets of genes are turned on or off in response to signals from other organisms or from the environment, and how multiple metabolic pathways are integrated to produce end products needed at particular times in the life of a cell or an organism. The MCB investment will advance genome-enabled research to promote fundamental understanding of the diversity of organisms making up the natural world and will contribute to applications in biotechnology, agriculture, and the environment.
  
  
• Example: MCB has supported studies of cell to cell chemical signaling in bacteria, and its effects on expression of genes affecting their population dynamics and adaptive responses. Bacteria have been found to produce, release, detect and respond to signaling molecules that accumulate in the environment as the cell population increases. In the light-emitting bacterium Vibrio harveyi separate chemical signals have been discovered for communication between cells and between this and other species. Genomic analysis has shown that genes involved in these responses are found in over thirty species of bacteria. Thus, communication using this type of signaling system may be a common mechanism that bacteria employ for interacting in natural environments. These signaling systems have now been shown to operate in related organisms of concern for public health, such as the organisms that cause typhoid fever and cholera.
  
  
• Microbial Biology: Use of genetic and biochemical approaches in addition to genomic approaches to characterize such basic attributes of complex microbial systems represent steps toward developing integrated models of microbial behavior, predicting microbial responses to environmental factors, and planning and understanding the results of long term studies of microbes in the environment such as are being supported through the Microbial Observatories activity. These efforts are consistent with priorities of the coordinated interagency coordinated effort, "The Microbe Project." The Microbe Project is enhancing knowledge of microbes by building needed infrastructure, promoting research and developing human resources and an informed public. Participating agencies include the USDA (lead), CIA, DoD, DOE, USGS, EPA, FDA, NASA, NIH, NIST, NOAA and NSF. In FY 2001, a special competition to support the DNA sequencing of microbes important in basic research and agriculture was jointly managed by NSF and USDA.
  
  
• "2010 Project:" The MCB Subactivity will continue to support research enabled by the availability of the complete genome of Arabidopsis to determine the functions of all the genes of this model flowering plant by the year 2010.
  
  
• Systems Biology: 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, macromolecular complexes, and cellular processes; in modeling and simulation of the regulation and relationships of cellular and metabolic processes; in analysis of genome data; and in other applications in genetics and functional genomics. Perhaps the greatest computational challenges facing the 21st Century Biology involve creation of multi-scale models, which can incorporate our new understanding of structure and interactions at all levels into a predictive whole. MCB will continue to encourage integration of these approaches with experimental research on molecules and cells in a wide range of biological systems to permit the conceptualization of complex biological systems. MCB priorities include development and application of new analytical tools for study of biological molecules and cells.