Bree Aldridge
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 Bree Aldridge ([BE] doctoral)
Ph.D. Advisors: Douglas Lauffenburger (Biological Engineering, MIT) and Peter Sorger (Department of Systems Biology, Harvard Medical School) Education Ph.D Biological Engineering, Massachusetts Institute of Technology, 2008, Research My research goals focus on understanding the mechanisms which make cellular signaling networks precise yet flexible by combining experiments with mathematical analysis and interpretable modeling. Computational models of signaling pathways are tools that help us quantitatively explore complex signaling networks. One method to decipher entangled signals is to characterize the signals that influence cell decisions. For ordinary differential equation-based models, several methods exist to study steady state signals that lead to different cell fates. However, some signal transduction networks influence cell decisions through transient signals before the network returns to its steady state. We employ computational methodologies augmented from dynamical systems and fluid mechanics to quantitatively analyze transient signals and relate them to different cell fates. Complexity is another obstacle in understanding signaling pathways. Often, a mechanistic model is too large and intertwined to interpret, even with the aid analysis tools. We are developing modeling techniques aimed at improving modeling usability and interpretability. We employ logic-based and hyrbid modeling methods that are quantitative, easy to manipulate, and incorporate known and hypothesized signaling interactions. Another project involves using mathematics and modeling to interpret quantitative data in studying chormosome segregation. My part of the collaboration involved developing an analysis technique using singular value decomposition and Shannon entropy to quantify orderliness of kinetochore-kinetochore axes in dividing cells. Publications "Quantitative analysis of pathways controlling extrinsic apoptosis in single cells." Albeck, J. G., Burke, J. M., Aldridge, B., Zhang, M. S., Lauffenburger, D. A., and Sorger, P. K. Molecular Cell (2008). 30: 11-25. [full text] "Physicochemical modelling of cell signalling pathways." B. Aldridge, J. Burke, D. Lauffenburger, P. Sorger. Nature Cell Biology. (2006) 8, 1195-2003. [full text] [podcast] "Direct Lyapunov Exponent Analysis Enables Parametric Study of Transient Signaling Governing Cell Behavior." B. Aldridge, G. Haller. P. Sorger, D. Lauffenburger. Systems Biology (2006) 6, 425-432. full text. [Supplementary materials] [SIAM news article] "Misorientation and reduced stretching of aligned sister kinetochores promote choromosome missegregation in EB1 or APC-depleted cells." V. Draviam, I. Shapiro, B. Aldridge, P. Sorger. EMBO J. (2006) 25, 2814–2827. [full text] [MIT news story] Funding [DOE Computational Science Graduate Fellowship] Collaborators |
