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Nick Flann is an Associate Professor in the Department of Computer Science at Utah State University (USU) and in 2010 completed a sabbatical at ISB in the Shmulevich lab.
Systems biology has been successful in understanding cell components and their complex interactions through the integration of high throughput data sources with computational analysis. The challenge is to extend systems biology over multiple scales to comprehend how subcellular processes control cell behavior and in turn, how interactions among cells lead to large scale organization at the tissue level. Such knowledge is key to unlocking the genetic foundations of morphological development and disease.
Dr. Flann's research interests lie in developing mechanistic multiscale models that bridge the gap between regulatory network dynamics and morphological outcomes. The work focuses on applying high-fidelity methods that implement the diversity of cell physiology, not directly as high level descriptions, but as combinations of modular subcellular mechanisms. One such modeling approach is the Cellular Potts Model (CPM) that represents 2D and 3D cellular systems as lattices of simple mesoscopic particles and model components as additive energy terms over cell and sub-cell configurations. The advantage for multiscale modeling is in its simplicity and realism since, just as in living systems, organization at the cell, multicell and tissue scale emerges through the complex interaction of lower-level mechanisms.
Areas of Research:
Research in Dr. Flann's lab is directed to the development and application of multiscale models to significant biological subsystems in cancer, immunity and yeast colony development. Through active collaboration with multiple labs at ISB, common application-independent methodologies are being developed and applied to these specific domains as pilots systems. Some of the questions driving the research are:
Key collaborations within ISB:
Ilya Shmulevich: Projects include: (a) a multidisciplinary study of how glioma development is influenced by the interactions among the immune, vascular and micro-tumor systems. This work is in collaboration with Dr. Wei Zhang at MD Anderson Cancer Center and involves the integrated of in vitro experimentation, image analysis and multiscale modeling; (b) understanding criticality at multiple scales in morphological and disease development; and (c) the designing of new methods for model fitting and validation from multiscale images.
Aímee Dudley: Projects include: (a) the development of computational frameworks that tightly integrate whole yeast colony simulation with high-throughput experimentation; and (b) the application of multiscale models to understand sub-colony structure formation including carbohydrate matrix and its role in the development of complex and distinct colony features such as ridges, folds and aerial tubes.
Adrian Ozinsky: Projects include model-based cell tracking from in vitro time-lapse images of epithelial to mesenchymal cell transitions to understand mechanisms of transition and discover possible precursor morphology and physiology clues that predict state changes.
Flann, N. S., Mahoney, A. W., and Podgorski, G. J. (2010) A Multi-Objective Optimization Based-Approach for Discovering Novel Cancer Therapies, IEEE/ACM Transactions on Computational Biology and Bioinformatics, May. 2010. IEEE Computer Society, http://doi.ieeecomputersociety.org/10.1109/TCBB.2010.39
Calmelet C., Flann N. S., & Sepich D., (2010) Notochord Development in Zebrafish. In Proceedings of 10th International Symposium on Mathematical and Computational Biology, 2010.
Flann N. S., Mahoney A. W., & Smith B. G., and Podgorski G. J. (2008). Evaluating Cancer Interventions by Simulating Tumor-Induced Angiogenesis, Blood Flow and Oxygen Delivery. In European Conference on Mathematical and Theoretical Biology.
Flann N. S., Mahoney A. W., Podgorski G. J., and Smith B. G. (2008). Discovering Novel Cancer Therapies: A Computational Modeling and Search Approach. In IEEE Conference on Computational Intelligence in Bioinformatics and Bioengineering, pp 233 - 240, November 2008. DOI: 10.1109/CIBCB.2008.4675785
Bansal, M., Podgorski, G. J., and Flann, N. S. (2007). Regular Mosaic Pattern Formation: A Study of the Interplay between Lateral Inhibition, Apoptosis, and Differential Adhesion. In Journal of Theoretical Biology and Medical Modeling, 2007, Volume 4:43 doi: 10.1186/1742-4682-4-43.
Dhanasekaran, R., Flann, N. S., and Podgorski, G. (2007). Co-option and Irreducibility in Regulatory Networks for Cellular Pattern Development. In Proceedings of First IEEE Symposium on Artificial Life 2007, Honolulu, Hawaii. DOI: 10.1109/ALIFE.2007.367794
Bansal M., Flann N. S., Hu J., Patel V., and Podgorski G. J. (2005). Biological Development of Cell Patterns: Characterizing the Space of Cell Chemistry Genetic Regulatory Networks, Eighth European Conference on Artificial Life, Canterbury, Kent, UK, September 2005. DOI: 10.1007/11553090_7