Monday, February 25, 2008

ICMSB 2008: Poster Session (N1 to N9)

International Conference on Mollecular Systems Bioloy (ICMSB 2008)
25 -28 February 2008
University of the Philippines-Diliman

Poster Sessions: N1 to N9

Venue: Ateneo de Manila University


[N1]: Regulation of the FNR System
D. Tolla and M. Savageau


The long-term goal of this work is to characterize the relationship between cycling and physiology of the FNR network of Escherichia coli. In this report, we formulate a model of this system, fit its parameters to existing experimental data, and predict results that were not used in the fitting. The results show excellent agreement between predictions and experimental data.

[N2]: Avoiding Catabolite Repression using Systems Biology
A. Sevilla, M. Canovas, C. Gonzalez-Alcon, N.V. Torres-Darias, and J.L. Iborra


Signal transduction pathways are usually avoided when optimizing a biotransformation process since they require complex mathematical formulations. The aim of this work was to use a Systems Biology approach to optimize and monitor the biotransformation of L-carnitine using signal transduction pathways. To this end, a dynamic model was constructed, integrating the metabolic pathways of L-carnitine biosynthesis as well as the expression of this metabolism by means of its regulation by transcription factors such as cAMP-CRP and CaiF. The model was validated using different C-sources as well as different reactor feeding approaches. A linear relationship between the external cellular cAMP and the L-carnitine production levels was predicted before being experimentally confirmed in several scenarios. Moreover, results of the model simulations and subsequent experimental findings demonstrated that the addition of exogenous cAMP was able to restore the L-carnitine production when glucose was used as C-source

[N3]: Mathematical Analysis of the Dynamics of a Single-Strain HIV Model with Multiple Endemic States

L.K. Faina, L. Almocera, and P. Sy


We analyze a third order autonomous, nonlinear system of ordinary differential equations modeling the dynamics of a single-strain HIV. We establish boundedness of
solutions and positive invariance of a certain region Γ in the nonnegative orthant. We show the existence of the disease free equilibrium and the multiple endemic states for a certain range of parameter values. We also compute the basic reproduction number R0 and show its relation to the stability of the steady states. We carry out numerical
simulations to show the possible bifurcations that the system undergoes.

[N4]: Exploring Characteristics of Metabolic Networks Lactococcus lactis IL1403
I-F Chung, S-Y Yang, S-Y Huang, and F-S Wang


In this study, we take lactic acid bacteria (LAB) as an example to explore characteristics of metabolic networks by two processes. Firstly, we adopt inverse flux analysis to obtain the whole internal regulations of LAB metabolic networks. In this way, it is easier to infer the unknown metabolic flux from the known ones and view the flux changes of the integral metabolic networks by interfering with some metabolic flux. Furthermore, we use elementary flux modes (EFMs) combining quadratic programming approach to reconstruct physiological flux distributions of fermented metabolism in LAB, attempting to find out the significant pathways of the main products.

[N5]: Halobacterium salinarum R-1 Metabolism: Reconstruction, Modeling & Analysis
O. Gonzalez, S. Gronau, M. Falb, F. Pfeiffer, E. Mendoza


We present a genome-scale metabolic reconstruction for the extreme halophile Halobacterium salinarum. The reconstruction represents a summary of the knowledge regarding the organism's metabolism and has already led to new research directions and improved the existing annotation. We used the network for computational analysis and studied aerobic growth of the organism using dynamic simulations in media with 15 available carbon and energy sources. Simulations resulted in predictions for the internal fluxes which describe at the molecular level how the organism lives and grows. We found numerous indications that cells maximized energy production even at the cost of longer term concerns such as growth prospects. Simulations showed a very low carbon incorporation rate of only ~15%. All of the supplied nutrients were simultaneously degraded, unexpectedly including five which are essential. These initially surprising behaviors are likely adaptations of the organism to its natural environment where growth occurs in blooms. In addition, we also examined specific aspects of metabolism, including how each of the supplied carbon and energy sources is utilized. Finally, we investigated the consequences of the model assumptions and the network structure on the quality of the flux predictions.

[N6]: Location of Malaria Infection in Cells through Grammatical Evolution of Image Processing Techniques (MICE)
C. Clarin and P. C. Naval


Malaria is one of the most important to address among all the tropical diseases. Over two billion people are at risk of infection and at least a million people die every year cite. Over the years, the most common tool in investigating malaria infection is the blood film examination. This paper proposes a grammatical evolution approach in automatically generating an image analysis JAVA program which effectively detects and locates malaria infection in blood smear images. After detection and location, the system should immediately get the ratio of infected over healthy cells to serve as quantification of parasite density in the blood.
This study is relevant in that it aims to lessen and speed up the labor intensive process of manually analyzing bulk image samples. It should also produce results which are competitive with the efficiency and accuracy of malaria detection operation and reference personnel. Consequently, the JAVA codes from the system should evolve to effectively analyze images subjected under different conditions such as laboratory preparation, image magnification, light orientation etc.

[N7]: In Silico Dynamical Analysis of Cellular Systems: A Molecular Perturbation Approach
T.M. Perumal, W. Yan, and R. Gunawan


The complexity of a typical cellular network limits the use of human intuition in understanding how functional regulation is accomplished in a cell. Mathematical modeling and analysis in systems biology offer a quantitative approach in tackling such problem. A novel dynamical analysis based on sensitivities to molecular perturbation is introduced. The result of this analysis can illustrate a dynamical picture on how regulation and/or signalling is accomplished in a given network. The analysis is then applied to a model of cell death regulation in jurkat T-cell line to show the usefulness of this new method.

[N8]: Identification of the biochemical response variables to glycerol pulse in E. coli by a multivariate approach
D.V. Guebel, M. Canovas, N.V. Torres-Darias


In a previous communication we presented some evidences (1) that glycerol uptake in E. coli under aerobic-batch culture conditions could occur through a membrane channel. Herein, by using a multivariate approach, we have analyzed the cellular response in terms of twelve biochemical variables after perturbation by a glycerol pulse of a steady, continuous E.coli culture operated in anaerobiosis, with high biomass density (2).
We concluded that in anaerobiosis glycerol is not taken-up by a Michaelian mechanism, but instead, shows a biphasic pattern with a sharp reduction in the influx rate (137 folds) despite the high glycerol external availability. This finding provides additional support to our previous claim that glycerol transport might be subjected to some kind of biochemical control rather than controlled by the instantaneous glycerol availability (i.e., the hysteresis effect).
Moreover, by using partial least squares regression (PLS) and Orthogonal Least Squares (OLS) correction –and in spite that all variables experienced significant variations after the pulse– we have identified which variables are primarily responsive to the glycerol perturbation. The most relevant findings arising from this analysis are: a) E. coli response does not imply a constant responsive structure along the monitored response period (120 min); b) At the early response step (0-5 min), after the extraction of the OLS, we detected 3 independent PLS factors; c) From these, only the first one has a close linear relationship with the glycerol input while the remaining behaved with an oscillatory, glycerol-independent pattern; d) Acetate production cannot be explained by the glycerol pulse, which implies that the overflow metabolism should be discarded as the cause of the acetate production; e) The NADH/NAD ratio showed a dual control: it is mainly glycerol-independent while in a lesser proportion is associated to the glycerol input; f) ATP strongly correlates with the glycerol input as well as ACS, ICL, ICDH enzyme activities and the formate yield. We conclude thus that at early response, ATP is mainly produced at the substrate level rather than from NADH oxidation. Moreover, given that the NADH/NAD ratio remained constant around 0.6, its behavior seems to be dissociated from the ATP dynamics; g) CHR enzyme showed also a dual pattern control since most of its changes are disconnected from the glycerol pulse, but a minor fraction it does; h) Carnitine biosynthesis shows also no correlation with the glycerol consumption rate, nor with the required CHR enzyme; i) Carnitine (which requires ATP for its synthesis) appears as independent of both, glycerol and ATP, whereas CHR has a strong correlation with ATP. Thus, CHR and ATP could not be limiting under the testing conditions; j) During early response, ethanol and lactate dynamics seems to be mutually independent being both also independent of the glycerol perturbation.
The next step in this investigation will be to integrate the obtained evidences in a general picture of E. coli physiology through its mathematical modeling, enabling thus a more rational manipulation of this microorganism.

[N9]: Agent-based models for biochemical systems
T-Y. Wang, K-C. Chen, D.F. Hsu, C-Y Kao


Motivation: Mathematical models in molecular systems biology are based on quantitative methods to describe the integrated behavior of complex biochemical networks. Such approaches often use variables and equations to model multiple components of the systems and their evolvements over time. Agent-based models provide another framework for complex biological systems, focusing on how individuals behave and what integrated behavior emerges. We are motivated to construct agent models for S-systems and explore the relations between them.
Results: To model a complex biochemical network, the
dynamics of integrated behavior is characterized by an S-system as a whole, and a large number of individual entities are considered as autonomous decision-making agents separately. Our goal is to establish the generalized birth-death processes of agents dominated by probabilistic rules such that the integrated influxes and effluxes can be expressed as multivariate power-law functions. Our agent-based models for biochemical systems are basic and provide an intuitive approach to complex systems more completely, including the process of integrated behavior emerges from individual interactions. It implies that advanced applications of mathematical models with agent-based modeling might be well suited to portray complex biochemical networks.

For more information, contact:

Dr. Rafael P. Saldaña
ICMSB 2008
Chair, Workshop on Systems Biology of Rice

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