[Federal Register Volume 71, Number 114 (Wednesday, June 14, 2006)]
[Notices]
[Pages 34376-34377]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-9301]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Institute of Allergy and Infectious Diseases; 
Cooperative Research and Development Agreement (CRADA) Opportunity for 
Furthering the Development of a Suite of Computer Programs for Modeling 
and Simulating Complex Cellular Biological Processes

ACTION: Notice.

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SUMMARY: The National Institute of Allergy and Infectious Diseases 
(NIAID), a component of the National Institutes of Health (NIH), 
Department of Health and Human Services (HHS), seeks to enter into a 
CRADA with a commercial partner to co-develop a suite of computer 
programs for modeling and simulating complex cellular biological 
processes.
    The existing suite of computer programs allows biologists to 
develop and test quantitative models of cell biological processes. The 
graphical interfaces of the programs make it possible to develop 
realistic models of molecular interactions and cellular processes that 
take into account the intracellular and extracellular spatial 
inhomogeneity of signaling components without the user having to deal 
with the partial differential equations and state automata that 
underlie the quantitative simulation of the models. The program suite 
offers graphical symbols and drag-and-drop mechanisms to define 
molecular interactions, molecular complexes, cellular stimulus-response 
mechanisms, and the structure of extracellular compartments. An 
intuitive graphical interface can be used to inspect and interact with 
running simulations; for example, molecules and cells can be placed 
into the simulated compartments, cells can be selected for detailed 
analysis of their behavior and intracellular, spatially-resolved 
biochemistry. One part of the program suite reads the molecular 
interaction network data that are generated by the program based on the 
user defined bimolecular interactions and displays them as interaction 
graphs, visualizing the reaction dynamics in the modeled cellular 
signaling pathways.
    It is anticipated that the collaboration will result in the 
commercialization of the software.

DATES: NIAID will consider all capability statements received within 45 
days of the date of publication of this notice. Capability statements 
received thereafter may be considered if a

[[Page 34377]]

suitable CRADA collaborator has not been selected.

FOR FURTHER INFORMATION CONTACT: Queries and capability statements 
should be addressed to William C. Ronnenberg, JD, M.I.P., Office of 
Technology Development, National Institute of Allergy and Infectious 
Diseases, 6610 Rockledge Drive, Room 4071, MSC 6606, Bethesda, MD 
20892-6606 (Zip Code for Courier: 20817), telephone 301-451-3522, fax: 
301-402-7123, e-mail: [email protected].

SUPPLEMENTARY INFORMATION: With the increased availability of detailed 
proteomic data, the main obstacle to developing realistic software-
based simulation models of cellular signaling processes is the 
technical difficulty of transforming complex biological models into 
quantitative simulations. Biological models typically describe cellular 
signaling processes in terms of bimolecular interactions or the 
interaction between specific sites on two proteins. These bimolecular 
interactions can be integrated by available software into diagrammatic 
representations of signaling pathways. However, these descriptions are 
generally qualitative and are not useful for a quantitative 
understanding of the underlying biological systems. For quantitative 
representations of biological models, the current approach is to ask 
theorists (mathematicians, physicists, etc.) to transform these 
qualitative models into sets of equations or automata rules that 
roughly reflect the properties of the original model. The resulting 
descriptions of complex biological models are frequently inadequate 
because the theorist involved lacks an understanding of biological 
details or the resulting mathematical descriptions are over-simplified.
    The goals of the proposed CRADA are to integrate an existing 
software program for the simulation of multi-scale, cellular, 
biological models with protein database interfaces and to improve the 
software's graphical user interface. NIAID has developed, in part, 
software that simulates reaction networks of all possible molecular 
interactions in biological systems based on user inputs. The current 
development stage of the software combines several unique features, 
such as a graphical interface for the definition and simulation of cell 
biological models spanning the scale from bi-molecular interactions to 
the behavior of cell populations. Its internal algorithms for the 
integration of the partial differential equations governing the spatio-
temporal behavior of the simulated biological system use state-of-the-
art approaches to deal with very large reaction networks and the 
stiffness of the equations.
    Simulations created with the software take into account the 
differential behavior of cytosolic and membrane-bound complexes as well 
as transmembrane signaling events and generates the equivalent of a set 
of partial differential equations describing the spatio-temporal 
dynamics of the system. The graphical user interface of the software 
allows the user to define bi-molecular interactions, enzymatic 
transformations, (initial) spatial distribution of the components of 
cellular biochemistry and the location of cells within extracellular 
spatial compartments. Based on the initial distribution of molecules 
and cells defined by the user the software then simulates the behavior 
of the system providing a range of different graphical and tabular 
representations of the system's evolving state. At any time during the 
simulations, the user can add components (cells, molecules) and query 
the detailed biochemical state of cells (localized concentrations of 
signaling components) and investigate how these correlate with the 
cells' behavior.
    The capability statement must address, with specificity, each of 
the following selection criteria:
    (1) A demonstration of expertise and experience in the areas of 
design and coding of biological software with an extensive GUI 
component, as well as the development of supporting documentation;
    (2) A demonstration of and a willingness to commit reasonable and 
adequate resources (including facilities, equipment, and personnel) the 
development of this technology;
    (3) A demonstration of the expertise and ability to commercially 
develop, produce, sell, and provide user support for similar 
technologies; and
    (4) Ability to provide adequate and sustained funding for CRADA 
activities.

    Dated: June 2, 2006.
Michael R. Mowatt,
Director, Office of Technology Development, National Institute of 
Allergy and Infectious Diseases, National Institutes of Health.
[FR Doc. E6-9301 Filed 6-13-06; 8:45 am]
BILLING CODE 4140-01-P