Numerical Tools for analyzing cell signalling circuits in normal and tumor cells

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$300,000.00
Award Year:
2009
Program:
STTR
Phase:
Phase I
Contract:
1R41EB008414-01A1
Award Id:
93739
Agency Tracking Number:
EB008414
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
NUMERICA TECHNOLOGY, INC., 11 CAMBRIDGE CENTER, CAMBRIDGE, MA, 02142
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
157645537
Principal Investigator:
PAUL JASPER
() -
PJASPER@NUMERICATECH.COM
Business Contact:
PAUL JASPER
() -
Research Institution:
HARVARD UNIVERSITY (MEDICAL SCHOOL)

HARVARD UNIVERSITY
MEDICAL SCHOOL CAMPUS
BOSTON, MA, 2115

Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): Numerical Tools for analyzing cell signaling circuits in normal and tumor cells The proposal, part I of a phased STTR award, describes the development of software tools, workflow and proof-of-principle case studies for detailed kinetic modeling of cell signaling pathways (and similarly complex biological processes). The most critical step in building kinetic models of real biological processes is optimizing the match between model prediction and experimental data. Achiev ing this optimization requires efficient means to explore alternative pathway topologies (which give rise to the structure of the model) and to calibrate models to data (which constrains model parameters). We address both of these problems with particula r emphasis on the algorithms and software needed to perform calibration of highly parametric models based on deterministic ordinary differential equations. The size of these models, the incompleteness of experimental data, and the wide range of time scales makes effective extremely calibration challenging both in theory and in practice, making the proposal innovative and significant with respect to both its biology and its applied mathematics The project is a close collaboration between a software company ( Numerical) with deep expertise in chemical modeling, combustion engineering and numerical simulation and two systems biology groups (Sorger and Gunawardena) with expertise in experimental biology and computer science respectively. Three phase I specific ai ms include (1) Development of the Lisp-based little b programming environment as a means to represents biological pathways and multi-component protein complexes in a rapidly- revised, reusable form suitable (2) Optimizing numerical analysis tools for calib ration of biological models with a sophisticated workflow and new algorithms for adjoint-based sensitivity analysis and global parameter estimation (3) Methods for validating models and applying key findings to significant problems in systems pharmacology and drug discovery.

* information listed above is at the time of submission.

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