Biological systems, such as those controlling circadian clocks are highly complex and cannot be fully understood without computational methods. Mathematical modeling, simulation, and analysis are important tools in biological discovery. In our lab, we focus on model-building and analysis for oscillators in general and circadian clocks, specifically.
- Neil Sefah and Makoto Kinoshita - Neil and Makoto are using delay differential equations to understand how the timing of the intercellular signal in the mammalian clock and the timing of its receptor affects synchrony.
- SR Taylor, TJ Wang, D Granado-Fuentes, ED Herzog, Resynchronization dynamics reveal that the ventral entrains the dorsal suprachiasmatic nucleus, J. Biol. Rhythm., accepted.
- NJ Kingsbury, SR Taylor, MA Henson, Inhibitory and excitatory networks balance cell coupling in the suprachiasmatic nucleus: a modeling approach, J. Theor. Biol., 397:136-144, 2016.
- PC St John, SR Taylor, JH Abel, FJ Doyle III, Amplitude metrics for cellular circadian bioluminescence reporters, Biophysical Journal, 107:2712-2722, 2014.
- SR Taylor, A Cheever*, SM Harmon*, Velocity response curves demonstrate the complexity of modeling entrainable clocks, Journal of Theoretical Biology, 363:307-317, 2014 (* Colby student)
- SR Taylor, How to Get Oscillators in a Multicellular Clock to Agree on the Right Period, Biophysical Journal, 106:1839-40, 2014
- AB Webb*, SR Taylor*, KA Thoroughman, FJ Doyle III, ED Herzog, Weakly Circadian Cells Improve Resynchrony, PLoS Computational Biology, 8:e1002787, 2012 (*Equal contribution)
- H Mirsky, SR Taylor, RA Harvey, J Stelling, FJ Doyle III, Distribution-Based Sensitivity Metric for Highly-Variable Biochemical Systems, IET Systems Biology, 5:50-57, 2011
- SR Taylor, AB Webb, K Smith*, LR Petzold, FJ Doyle III, Velocity Response Curves Support the Role of Continuous Entrainment in Circadian Clocks, J. Biol. Rhythm., 25:138-49, 2010 (* Colby student)
- SR Taylor, FJ Doyle III, LR Petzold, Oscillator Model Reduction Preserving the Phase Response: Application to the Circadian Clock, Biophys. J., 95:1658-1673, 2008
- N Bagheri*, SR Taylor*, K Meeker, LR Petzold, FJ Doyle III. Synchrony and Entrainment Properties of Robust Circadian Oscillators, J. R. Soc. Interface, 5:S17-28, 2008
- SR Taylor, R Gunawan, LR Petzold, and FJ Doyle III. Sensitivity Measures for Oscillating Systems: Application to Mammalian Circadian Gene Network, IEEE Trans. Automat. Contr., 153:177-188, 2008
- MN Zeilinger*, EM Farre*, SR Taylor, SA Kay, and FJ Doyle III. A novel computational model of the circadian clock in Arabidopsis that incorporates PRR7 and PRR9. Mol. Syst. Biol. 2:58, 2006 (* Equal contribution)
Itrat Akhter (2015-2016) - Itrat expanded the test cases for the network inference projects and began a new project that aimed to understand the light-induced split between the core and shell of the mammalian circadian master clock.
Joseph Malionek (2015) - Joseph modeled the light-induced split between the core and shell of the mammalian circadian master clock.
Olivia Lang (2013-2014) - Olivia combined four previously analyzed models of the fly circadian clock. Her goal was to determine which mechanisms caused the original models to have particular, striking differences.
Devon Cormack (Honors, 2014) - Devon implemented a network inference algorithm to apply to recordings from mammalian brain tissue and evaluated its effectiveness with a mathematical model of the brain tissue.
Audrey Lyman (2014) - Audrey analyzed bioluminescence recordings of slices of mammalian brain tissue.
Roxana Gheorghe (2013) - Roxana simulated networks of circadian oscillators with the goal of infering network connections. She monitored the phase behavior of the cells as they transitioned from disorder to order.
Zachary Cecere (Honors, 2013) - Zack studied networks of circadian oscillators and determined that populations synchronize most readily when cells are capable of altering both their phase sensitivity and amplitude when signaled.
David Quigley (2011) - Dave studied networks of circadian oscillators. In particular, he explored the relationship between the period of an individual pacemaker's oscillation and the period of the synchronized network's oscillation. He showed that the relationship was highly complex and, often, counter-intuitive.
Allyson Cheever and Sarah Harmon (2010-2011) - Allyson and Sarah analyzed the phase response properties of fly circadian clock processes. They compared the behaviors of analagous processes in different mathematical models, looking for the underlying themes in the design. Their work has been published in the Journal of Theoretical Biology.
Andrew Cox (Honors, 2010) - Via parameter optimization, Andrew improved a single cell model of the mammalian circadian clock. Using his parameter set, multi-cell simulations mimick biological experiments that the published set could not capture. Here is his thesis.
Sarah Harmon (2010) - Sarah did interdisciplinary research with psychology, examining the role of gender in human-robot interactions. Presenting this work, Sarah won the second place prize at the ACM undergraduate student research competition at the Grace Hopper Celebration of Women in Computing (Sep 2010).
Hannah Coulson (2010) - Hannah performed a sensitivity analysis of a recent model of the mouse circadian clock. Her analysis should lead to insights into the relative contributions of the various interlocked feedback loops comprising the clock. This is an important endeavor because it is the first anaylsis of a model fit to single cell (rather than tissue data).
Olena Marchenko (2009) - Olena augmented a mathematical model of the circadian clock in the plant Arabidopsis thalian to include a new regulatory loop. Addition of the new loop should improve the predictive capability of the current models.
Katherine Smith (2009) - Katherine has shown that realistic phase-only models of the mouse circadian clock can entrain to natural, highly variable light/dark cycles. Her work has been published in the Journal of Biological Rhythms.