INTEGRATIVE BIOLOGY AND NEUROSCIENCE $98,726,000

The FY 2003 Budget Request for the Integrative Biology and Neuroscience (IBN) Subactivity is $98.73 million, a decrease of $2.69 million, or 2.7 percent from the FY 2002 Current Plan of $101.42 million.

(Millions of Dollars)

Research supported by the Integrative Biology and Neuroscience Subactivity seeks to understand the living organism - plant, animal, and microbe - as a unit of biological organization; and integrates genomic, molecular, biochemical, and biophysical approaches to the understanding of the development, function, neurobiology, and behavior of living organisms. The emphasis is on understanding the physiological and biochemical mechanisms through which an organism adapts to changing environmental conditions. IBN supports the development and use of a wide diversity of organisms to assist both in identifying unifying principles common to all living beings and in documenting the variety of mechanisms that have evolved in specific organisms. Genome-enabled science and systems biology will complement other strategic approaches to investigate how organisms carry out basic biological processes.

In FY 2003, activities in the IBN Subactivity are decreased by $2.69 million. This reflects the restructuring of the BIO budget structure to establish the new Emerging Frontiers Subactivity, which was established as an incubator for evolving multidisciplinary research and networking activities. Within the budget request, IBN will include enhanced support for:

21^st Century Biology: The overarching goal of biology is to understand life at both its most fundamental level and in all its complexity. Exciting advances and integration of advances in genomics, proteomics, informatics, computer science, mathematics, physics, chemistry, and engineering offer the promise of realizing these ambitious goals. IBN will support 21^st Century Biology research to discover the functioning of genes within organisms and in the environment, the evolution of development, and computational biology.

• Functional Genomics: IBN will focus on the support of integrative approaches to the study of plant and animal form and function at the organismal, organ, and tissue levels of organization. Integrated studies will yield information and models that can provide insight into the interaction of biological, physical, and behavioral systems.
  

  Example: The flowering time of many species of plants is affected by temperature and day length. Understanding these phenomena has been aided by the cloning and characterization of one of the genetic loci responsible for the late-flowering habit of Arabidopsis winter annuals. This locus (FLC) encodes a transcription factor, which acts through repression of other, "downstream" genes in the flowering pathway. A number of FLC-related genes have also been cloned and sequenced. Determination of the molecular basis of the regulation of FLC by some of these genes, and of its mode of action in mediating flowering pathways in Arabidopsis, will provide a basis for understanding flowering time regulation in other plants.

• Evolution of Development: Recent conceptual and technical advances in developmental biology have led to new developmental approaches to the understanding of phylogeny. The genes directing the development of all metazoan organisms have been shown to be strikingly similar. The core set of these genes and gene families is relatively small, and changes in the program of their expression can cause dramatic changes in animal and plant form. IBN will support research to study how these genes and gene families work in different species, research to elucidate how gene duplication and divergence alters developmental mechanisms, and studies of the role genome modification plays in co-evolution of species.

  Example: Studies of the development of two different sea urchin species have shown how surprisingly fast dramatic evolutionary changes in animal form can occur. The two urchins very closely resemble each other as adults but go through very different patterns of development and the juveniles look very different from one other. When hybrids of these two species are formed, a surprising juvenile form results that resembles a starfish more than either sea urchin. It has been assumed that evolutionary change in animal form occurs very slowly, over geological timescales. The dramatic result of this laboratory-induced combining of evolutionary programs, however, demonstrates that evolutionary change may occur rapidly in nature.

• Computational Biology: Computational biology is part of a larger revolution that affects how all of science is conducted. This is being driven by the generation and use of information in all forms and in enormous quantities. Computational biology deals with two pressing needs, the management and the analysis and interpretation of biological information. Characterization of biological systems has reached an unparalleled level of detail. To organize this detail and achieve integrative understanding of fundamental life processes, it is imperative that powerful computational approaches be applied to the frontier problems in biology. IBN will support research that utilizes advanced computational approaches and tools to understand biological systems in all their complexity.