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Systems analysis has become a requirement for making sense
of high-throughput data and for characterizing properties of biological
networks. In order to extend these recent developments to medical
applications, there is a pressing need for reconstructing and analyzing the
signaling networks that direct cellular processes. Basically, we need to
quantify how cells communicate with each other, a critical component of many
human health problems as diverse as cancer and infectious disease.
In short, our research goal is the stoichiometric
reconstruction and analysis of large-scale signaling networks and their
application to human disease. Two primary questions drive our research: (1)
How do network properties of a single cell emerge from the collection of
components and interactions, and (2) How does a single cell function in its
multi-cellular context?
Specifically, we have on-going projects in the following
areas:
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Intracellular signaling networks.
We are reconstructing the genome-scale cellular signaling networks of
Saccharomyces cerevisiae and the human B-cell and macrophage. These
reconstructions are critical for our efforts to integrate high-throughput
data like protein-protein interaction maps and gene expression arrays into a
cohesive and quantifiable framework. Diseases of particular interest
include B-cell lymphomas.
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Recent publications |
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Papin, J.A.,
T. Hunter, B.O. Palsson, and S. Subramaniam. 2005. Reconstruction of
cellular signalling networks and analysis of their properties.
Nature Reviews Molecular Cell Biology, 6: 1-13. [PubMed
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Abstract |
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Papin, J.A.,
and B.O. Palsson. 2004. The JAK-STAT signaling network in the human
B-cell: an extreme signaling pathway analysis. Biophysical Journal,
87: 37-46.
[PubMed
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Cell-cell signaling systems.
We are interested in how cellular signaling networks
interact with each other to in multi-cellular systems. In collaborative
work with several colleagues, we are reconstructing the signaling network
critical for vulval development in Caenorhabditis elegans, and developing
computational frameworks for analyzing multi-scale signaling processes (from
cell to tissue-level characterizations). These projects are critical for
tissue engineering applications and understanding cancer and developmental
disorders.
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Pathogen-host interactions.
We are reconstructing the metabolic and signaling networks for human
pathogens involved in polymicrobial disease processes, including Candida
albicans. This work addresses the challenges of how to account for
multiple interacting microbial species, similar to the challenge of
accounting for multiple interacting cells in a multi-cellular organism
described above. Furthermore, we are interested in public health challenges
as it relates to improving drug treatment of infectious disease for these
organisms.
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Recent publications |
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Papin, J.A.,
N.D. Price, J.S. Edwards, and B.O. Palsson. 2002. The genome-scale
metabolic extreme pathway structure in Haemophilus influenzae shows
significant network redundancy. Journal of Theoretical Biology, 215:
67-82. [PubMed] |
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Price, N.D., J.A. Papin, and B.O. Palsson. 2002.
Determination of redundancy and systems properties of Helicobacter pylori’s
metabolic network using genome-scale extreme pathway analysis. Genome
Research, 12: 760-769. [PubMed
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Abstract |
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Tools for network analysis.
Associated with the biological and medical application of
the three research aims above, we develop methods for quantifying cellular
network properties. We are developing approaches to: integrate signaling,
metabolic, and regulatory networks; generate stoichiometric reconstructions
from high-throughput data particular to signaling networks; and analyze
dynamic properties of genome-scale signaling systems.
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Recent publications |
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Gianchandani, E.P.,
J.A. Papin, N.D. Price, A.R. Joyce, and B.O. Palsson. 2006.
Matrix formalism to describe functional states of transcriptional
regulatory systems. PLoS Computational Biology, 2:
e101. [PubMed
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Abstract |
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Papin, J.A.,
J.L. Reed, and B.O. Palsson. 2004. Hierarchical thinking in network
biology: the unbiased modularization of
biochemical networks. Trends
in Biochemical Sciences, 29: 641-647. [PubMed] |
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Papin, J.A.,
N.D. Price, S.J. Wiback, D.A. Fell, and B.O. Palsson. 2003.
Metabolic pathways in the post-genome era. Trends in Biochemical Sciences,
28: 250-258. [PubMed] |
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Papin, J.A.,
J. Stelling, N.D. Price, S. Klamt, S. Schuster, and B.O. Palsson. 2004.
Comparison of network-based pathway analysis methods. Trends in
Biotechnology, 22:
400-405. [PubMed] |
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