Award Abstract #0425762
QSB: Computing Life and the Kinetics of the Cell

NSF Org:	CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems
Initial Amendment Date:	August 10, 2004
Latest Amendment Date:	January 24, 2008
Award Number:	0425762
Award Instrument:	Standard Grant
Program Manager:	Fred G. Heineken CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems ENG Directorate for Engineering
Start Date:	September 1, 2004
Expires:	August 31, 2008 (Estimated)
Awarded Amount to Date:	$499994
Investigator(s):	Jonathan Arnold arnold@arches.uga.edu (Principal Investigator) Heinz-Bernd Schuttler (Co-Principal Investigator)
Sponsor:	University of Georgia Research Foundation Inc 621-630 GRADUATE STUDIES ATHENS, GA 30602 706/542-5939
NSF Program(s):	MSPA-INTERDISCIPLINARY, BIOTECH, BIOCHEM & BIOMASS ENG, GENES AND GENOME SYSTEMS
Field Application(s):	0308000 Industrial Technology
Program Reference Code(s):	BIOT, 9181, 7303, 1757, 1116
Program Element Code(s):	7454, 1491, 1112

ABSTRACT

Arnold

0425762

The main goal of this research is to implement and validate a novel approach towards quantitative functional genomics, referred to as the computing life paradigm, which integrates state-of-the-art experimental probes of the time-dependent intra-cellular kinetics with a recently proposed ensemble-based kinetics modeling technique. Its starting point are quantitative RNA and protein profiling experiments to monitor the cell's responses to controlled external perturbations such as gene knock-outs, protein inhibition and various time-dependent schedules of external food sources and starvation. The ensemble modeling technique then utilizes such time-dependent experimental data to not only constrain the topology and the parameter space of the genetic network model(s) under study; but also to make quantitative predictions and, most importantly, to provide quantitative criteria for the rational design of a "maximally informative next experiment". The full implementation of the computing life paradigm thus results in a workflow cycle wherein rationally designed new experiments further constrain the "ensemble of models" while the model ensemble becomes more and more refined and discriminating in its predictive capabilities. The initial applications of this approach will focus on two previously well explored genetic model systems in fungal organisms, specifically in Neurospora crassa, exhibiting widely different dynamical behavior: the quinic acid (qa) gene cluster, involved in transient responses of the cell's carbon metabolism; and the biological clock, the proto-type of an oscillatory system.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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Deligiannidis, L, TR Taha, B Aleman-Meza, Y Yu, H.-B. Schuttler, & J Arnold.  "GKIN: a graphical user interface for KINSOLVER.,"  Proc. 2005 Inernational Arab Conference on Information Technology(ACIT?2005), Dec. 6-8, 2005, Amman, Jordan,  2005,  p. 245.

Dong, W, X Tang, Y Yu, J Griffith, R. Nilsen, D Choi, J Baldwin, L Hilton, K Kelps, J McGuire, R Morgan, M Smith, M Case, J Arnold, H-B Schuttler, Q Wang, J Liu, J Reeves, and D Logan.  "Systems biology of the Neurospora biological clock,"  IET Systems Biology,  v.1,  2007,  p. 257.

Dong, W, X Tang, Y. Yu, R. Nilsen, J. Griffith, J. Arnold, & H.-B. Schuttler.  "Systems biology of the clock in Neurospora crassa,"  PLoS One,  v.3,  2008,  p. 3105.

J. Arnold, W. Dong, J. Griffith, D. Choi, J. Baldwin, L. Hilton, K. Kelps, J. McGuire, R. Morgan, M. Smith, Q. Wang, J. Liu, J. Reeves, D. Logan, M. E. Case, and H.-B. Schuttler.  "Systems Biology of the Biological Clock,"  Proceedings of the First International Conference on Computational Systems Biology,  2006,  p. 119.

Logan, DA, AL Koch, W Dong, J Griffith, R Nilsen, ME Case, H-B Schuttler and J Arnold.  "Genome-wide expression analysis of genetic networks in Neurospora crassa,"  Bioinformation,  v.1,  2007,  p. 390.

M. Xiong and J. Arnold.  "Do genetic networks obey Kirchoff's and Ohm's Laws?,"  Proc. IASTED International Conference on Computational and SystemsBiology, Dallas, TX, November 13-14, 2006,  v.1,  2006,  p. 13.

Yu, Y, W. Dong, C Altimus, X. Tang, J. Griffith, M. Morello, L Dudek, J. Arnold & H-B Schuttler.  "A genetic network for the biological clock of Neurospora crassa,"  PNAS USA,  v.104,  2007,  p. 2809.

Yu, Yihai.  "Monte Carlo Studies of Genetic Networks with Special Reference to the Biological Clock of Neurospora crassa,"  University of Georgia Ph.D. Dissertation,  2005,  p. 1.


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