Oltvai Lab - Overview & ProjectsBiomedical research today is conducted largely in the context of an established paradigm that is fundamentally reductionist in nature. Yet, despite the enormous success of this approach, it is increasingly clear that discrete biological function and the astounding complexity of living systems cannot be understood by studying individual molecules. Instead, most biological characteristics arise from complex interactions among the cell's numerous molecular constituents. Thus, a key challenge for 21st century biology is to understand the structure and the dynamics of the complex intracellular web of interactions among the various types of molecules that contribute to the function and the physical entity of a living cell. Together with our collaborators, our laboratory focuses on the understanding of the system-level organization of cellular metabolism, and how environmental cues are processed through regulatory pathways leading to rearranged metabolic activities. In the long run, we are also interested in applying this knowledge to improved disease diagnosis and treatment.
Organization and Function of Metabolic NetworksThe metabolic activity of any cell can be reduced to a complex network of interacting molecules. In a network representation, any two metabolites that can be interconverted are viewed as nodes, and the biochemical reaction (and indirectly the corresponding catalytic enzymes), is the link that connects them. The totality of the metabolic substrate interactions that can be found in a given organism is determined by its genome-encoded enzyme compendium, and is referred to as that organism's metabolic network. Through a combination of experiments and mathematical approaches we aim to understand the principles that underlie the system-level organization of metabolism in the model bacterium, E. coli, and to predict its behavior in various growth environments.
- H. Jeong, B. Tombor, R. Albert, Z. N. Oltvai, and A.-L. Barabási, The large-scale organization of metabolic networks, Nature 407, 651-654 (2000).
- E. Ravasz, A. L. Somera, D. A. Mongru, Z. N. Oltvai, and A.-L. Barabási, Hierarchical organization of modularity in metabolic networks, Science 297, 1551-1555 (2002).
- S. Y. Gerdes, M. Scholle, J.W. Campbell, G. Balazsi, E. Ravasz, et al., Experimental Determination and System Level Analysis of Essential Genes in Escherichia coli MG1655, Journal of Bacteriology 185, 5673-5684 (2003)
- E. Almaas, B. Kovacs, T. Vicsek, Z. N. Oltvai and A.-L. Barabási, Global organization of metabolic fluxes in the bacterium Escherichia coli, Nature 427, 839-843 (2004).
Organization and Function of Transcriptional-regulatory NetworksCells sense and respond to environmental changes and internal cues through the activity of various molecular interaction networks. A characteristic feature of intracellular information transfer is that the components of the various regulatory networks operate over several orders of magnitude in time. The fastest of these comprise the various signal transduction networks, ranging from two-component systems of prokaryotes to the highly complex signal transduction networks of mammalian cells. Fast signaling, however, is frequently followed by slower transcriptional regulatory events, during which regulatory gene products, such as Transcription Factors and regulatory RNAs alter the rate of transcription of other genes, reorganizing gene expression to achieve new metabolic states, or initiate cellular programs, such as the cell cycle or sporulation. Through combined experimental and theoretical approaches we aim to understand the principles that underlie the system-level organization of transcriptional regulation in E. coli, and how it leads to the reorganization of metabolism in various growth environments.
- I. J. Farkas, H. Jeong, T. Vicsek, A.-L. Barabási, and Z.N. Oltvai, The topology of transcription regulatory network in the yeast, Saccharomyces cerevisiae, Physica A 318, 601-612 (2003).
- R. Dobrin, Q.K. Beg, A.-L. Barabási, and Z. N. Oltvai, Aggregation of topological motifs in the E. coli transcriptional regulatory network, BMC Bioinformatics 5: 10 (2004).
- G. Balázsi and Z. N. Oltvai, Sensing your surroundings: How transcription-regulatory networks of the cell discern environmental signals, Science STKE 5, pe20 (2005)
- G. Balázsi, A.-L. Barabási, and Z. N. Oltvai, Topological units of environmental signal processing in the transcriptional regulatory network of Escherichia coli, PNAS 102: 7841-7846. (2005)