E6-9301. 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 ...

ACTION:

Notice.

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 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 [phone], fax: [phone], e-mail: [e-mail].

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.