Beruflich Dokumente
Kultur Dokumente
Ziomara P. Gerdtzen, J. Cristian Salgado, Axel Osses, Juan Asenjo, Ivan Rapaport and Barbara Andrews
RIB2008 Pontificia Universidad Catolica October 15, 2008
Millennium Institute for Cell Dynamics and Biotechnology (ICDB) Department of Chemical Engineering and Biotechnology
University of Chile
Millennium Institute for Cell Dynamics and Biotechnology (ICDB) Department of Chemical Engineering and Biotechnology
University of Chile
The goal of our Institute is to conduct frontier research in cell function and dynamics and to develop models of important biological systems using a modern Systems Biology approach This holistic approach is being conducted by a multidisciplinary team of bioengineers, cell and molecular biologists, mathematicians, biochemists, chemists and computer scientists
The development of novel approaches in the field of Systems Biology that should result in original solutions to more traditional biological problems To have an impact on scientific problems of national as well as international importance
The application of the knowhow existing in the different groups of the Institute to the solution of problems of importance in Chile and abroad (Applied Research)
http://www.icdb.uchile.cl
Cyanobacteria
Aquatic and photosynthetic (blue-green algae) Can form colonies (filaments) Cell types:
Anabaena catenula
Differentiation to Heterocysts
One of every ten vegetative cells differentiates into nitrogen-fixing heterocyst Triggered by absence of a fixed nitrogen source Genes involved:
NtcA stimulates HetR expression HetR phosphorylated by PatA Indirect activation of genes for heterocyst development HetR protease, acts on PatS PatS peptide inhibits PatA
Time
Effect of D
Relationship between diffusion coefficients for PatS and Nitrogen, and the systems behavior
The average distance between heterocysts LH in the absence of nitrogen for wild type
Expression Profiles
Inhibitory action of neighboring cells on ntcA expression is reduced as LH increases Eventually, this expression is high enough to trigger cell differentiation
Effect of Perturbations
The systems response to disturbances on nitrogen levels, knock out of patS and over expression of hetR was studied Results were compared with experimental observations
A: High N
Some cells differentiate into heterocysts in the absence of nitrogen, with an LH ~10 cells
For patS knockouts the inhibitory effect of PatS is reduced, decreasing LH and allowing the formation of heterocyst clusters
HetR over expression leads the formation of heterocyst clusters, with a pattern similar to the one observed for patS knock outs
Over expression of hetR leads to the formation of heterocysts under normally repressing conditions
Conclusions
In presence of Nitrogen each cell has only one attractor (vegetative cell) In absence of Nitrogen there are several attractors where some cells differentiate (to heterocyst) The model allows quantification, computation of the differentiation distance as a function of the diffusion coefficient Captures key feature: LH ~10 cells between heterocysts
Conclusions
The model reproduces experimental results for over expression and knock out of patS and hetR Expression profiles are consistent with experimental data No assumptions on the range of action of the differentiation activator HetR and the inhibitor PatS
References
Adams, D.G. (2000). Heterocyst Formation in Cyanobacteria. Current opinion in microbiology 3(6): 618. Golden, J.W. and Yoon, H.S. (2003). Heterocyst Development in Anabaena. Current opinion in microbiology 6(6): 557. Hammel, M. and Prusinkiewicz, P. (1996). Visualization of Developmental Processes by Extrusion in Space-Time. Proceedings of Graphics Interface: 246. Haselkorn, R. (1998). How Cyanobacteria Count to 10. Science (New York, N.Y 282(5390): 891. Yoon, H.S. and Golden, J.W. (1998). Heterocyst Pattern Formation Controlled by a Diffusible Peptide. Science (New York, N.Y 282(5390): 935.
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