CCAM at UConn Health
CCAM integrates new microscope technologies for making quantitative in vivo live cell measurements with new physical formulations and computational tools that will produce spatially realistic quantitative models of intracellular dynamics.
To investigate the relationships between experimental and compuational worlds, we use a tripartite approach described as:
- Measure - develop new tools for measuring spatially resolved dynamic behavior of molecules in cells.
- Model - develop new methods for spatial modeling of biological systems.
- Manipulate - develop new techniques for manipulating the spatial distribution of molecules in living cells.
These three analytical approaches, (measurement, modeling and manipulation) are integrated and interdependent, e.g. models generate predictions that can be validated with new measurements, as well as experimental approaches that manipulate intracellular signals and structures. These approaches allow us to tackle fundamental questions of how the spatial organization of molecules in cell is established and how it is utilized to control cell function. CCAM hosts a confluence of expertise in physics, chemistry, experimental cell biology and software engineering immersed in a biomedical research setting that values interdisciplinary collaborations, and our Training Program in Cell Analysis and Modeling provides a new model for interdisciplinary training in cell biology. CCAM is the home of the Virtual Cell, a computational environment for cell biological modeling developed as a NIH-designated National Resource, and also hosts a variety of projects in biophotonics and live cell microscope imaging methods as well as a state-of-the-art user microscopy facility for nonlinear, confocal, and widefield microscopy.
Upcoming Events
CCAM Seminar Series - Froehlich
Thursday, October 17th, 2019
12:00 PM - 01:00 PM
UConn HealthCGSB, CCAM Conference Room, R1673, 400 Farmington Ave
Speaker: Fabian Froehlich Ph.D., Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School
Title: "Thermodynamic Modeling of ERK and EGFR signaling reconciles apparent drug interactions with molecular mechanisms"
Host: Dr. Michael Blinov
Abstract:Allosteric interactions are at the core of many signal transduction processes and provide robustness and enable context dependency for the underlying molecular mechanisms. In the context of RAF inhibitors allosteric interactions give rise to paradoxical activation, a clinically observed phenomenon where RAF inhibitors effectively decrease tumor growth in BRAF mutant cancers but promote tumor growth in BRAF wild-type cancers. Energy based formalisms to describe such allosteric effects in kinetic models have been developed, but are so far rarely applied in practice, which is likely to be a result from the high complexity of the generated models.
Here we demonstrate the use of a thermodynamic, energy-balanced rule-based formalism to describe allosteric interactions. We tackle the numerical challenges of large kinetic models by using state of the art simulation tools and address the conceptual challenge of analyzing large kinetic models by exploiting the strong structure imposed on the model by the rule-based formalism and energy balance.
We apply these methods to an ordinary differential equation model of adaptive resistance in melanoma (EGFR and ERK pathways, >1k state variables, >10k reactions). We trained the model on absolute proteomic and phospho-proteomic as well as time-resolved immunofluorescence data, both in dose-response to small molecule inhibitors. We identify and explain a time-scale separation between transcriptional feedbacks and phospho-signaling. Moreover, we illustrate how kinetic models can extrapolate from single drug treatments to drug combinations.
Contact Information: Tiffany Jespersen
MoreCAM Presentation - Li
Friday, October 18th, 2019
12:00 PM - 01:00 PM
UConn HealthCGSB, Demo Room, R1401, 400 Farmington Ave
Speaker: Yuezhe Li
Title: TBA
Contact Information: Tiffany x6103
MoreCAM Presentation - Blinov
Friday, October 25th, 2019
12:00 PM - 01:00 PM
UConn HealthCGSB, Demo Room, R1401, 400 Farmington Ave
Speaker: Michael Blinov
Title: TBA
Contact Information: Tiffany x6103
MoreCAM Presentation - Cauble
Friday, November 1st, 2019
12:00 PM - 01:00 PM
UConn HealthCGSB, Demo Room, R1401, 400 Farmington Ave.
Speaker: Meagan Cauble
Title: TBA
Contact Information: Tiffany x6103
MoreCAM Presentation - Yan
Friday, November 8th, 2019
12:00 PM - 01:00 PM
UConn HealthCGSB, Demo Room, R1401
Speaker: Ping Yan
Title: TBA
Contact Information: Tiffany x6103
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