Multiscale Modeling of the Mammalian Circadian Clock: The Role of GABA Signaling

Investigators
Michael A. Henson, Erik D. Herzog, Yannis Kevrekidis
Contact info (email)
yannisk@jhu.edu
1. Define context(s)
reveal new biological insights
Current Conformance Level / Target Conformance Level
Extensive
Primary goal of the model/tool/database

The goal of this project is to combine modeling, experiment and computation to unravel the effects of environmental conditions on the network topology, synchronization behavior and entrainment properties of the mammalian circadian clock. The project leverages our expertise in experimental determination of functional connectivity across circadian neuron populations, multicellular modeling of the circadian clock with heterogeneous networks of coupled neural oscillators and new computational tools for efficiently simulating large populations of networked heterogeneous cells.

Biological domain of the model
Biological oscillators
Structure(s) of interest in the model
Synchronized oscillators
Spatial scales included in the model
Genes to neural population
Time scales included in the model
Minutes to weeks
2. Data for building and validating the model
Data for building the model Published? Private? How is credibility checked? Current Conformance Level / Target Conformance Level
in vitro (primary cells cell, lines, etc.) Yes No Replicates Extensive
ex vivo (excised tissues)
in vivo pre-clinical (lower-level organism or small animal) Yes No Replicates Extensive
in vivo pre-clinical (large animal)
Human subjects/clinical
Other: ________________________
Data for validating the model Published? Private? How is credibility checked? Current Conformance Level / Target Conformance Level
in vitro (primary cells cell, lines, etc.) Yes No Replicates Extensive
ex vivo (excised tissues)
in vivo pre-clinical (lower-level organism or small animal) Yes No Replicates Adequate
in vivo pre-clinical (large animal)
Human subjects/clinical
Other: ________________________
3. Validate within context(s)
Who does it? When does it happen? How is it done? Current Conformance Level / Target Conformance Level
Verification PhD Student Weekly Testing with different scenarios Extensive
Validation PhD Student Monthly Comparison with data Adequate
Uncertainty quantification
Sensitivity analysis PhD Student Monthly Sensitivity calculations Adequate
Other:__________
Additional Comments
4. Limitations
Disclaimer statement (explain key limitations) Who needs to know about this disclaimer? How is this disclaimer shared with that audience? Current Conformance Level / Target Conformance Level
Limited to VIP and GABA neurotransmission and constant darkness conditions Users In papers and code distribution Partial
5. Version control
Current Conformance Level / Target Conformance Level
Adequate
Naming Conventions? Repository? Code Review?
individual modeler Yes No Yes
within the lab Yes No Yes
collaborators No No Yes
6. Documentation
Current Conformance Level / Target Conformance Level
Code commented? Yes
Scope and intended use described? Yes
User’s guide? No
Developer’s guide? No
7. Dissemination
Current Conformance Level / Target Conformance Level
Partial
Target Audience(s): “Inner circle” Scientific community Public
Simulations Private Box folder Papers None
Models Private Box folder Papers now, Biomodels soon None
Software Private Box folder Papers None
Results Private Box folder Papers None
Implications of results Skype meetings Papers None
8. Independent reviews
Current Conformance Level / Target Conformance Level
Adequate
Reviewer(s) name & affiliation: Stephanie Taylor, Colby College
When was review performed? Summers, 2018 and 2019
How was review performed and outcomes of the review? Verbal feedback leading to code changes
9. Test competing implementations
Current Conformance Level / Target Conformance Level
Insufficient
Yes or No (briefly summarize)
Were competing implementations tested? No
Did this lead to model refinement or improvement?
10. Conform to standards
Current Conformance Level / Target Conformance Level
Adequate
Yes or No (briefly summarize)
Are there operating procedures, guidelines, or standards for this type of multiscale modeling? None generally accepted
How do your modeling efforts conform? We use MATLAB