Fall 2016
Seminars are held at 11:30AM in Cullimore Hall, Room 611, unless noted otherwise. For questions about the seminar schedule, please contact Casey Diekman.
Date: October 25, 2016
Speaker: Arjun Yadaw
Icahn School of Medicine at Mount Sinai,
Title: "A Comprehensive, Multi-Scale Dynamical Model of Cannabionoid (CB1) Receptor Regulated Neurite Outgrowth"
Abstract:
The outgrowth of neurites is a complex whole cell level process by which a neuron starts to acquire the morphological and functional capability for information transmission over a long distance. Such a change in cellular state depends on the coordinated functioning of multiple sub-cellular processes at different levels. A major question is how these subcellular processes act in a coordinated manner to produce this whole cell response.
To identify the sub cellular processes associated with neurite outgrowth, Neuro 2A cells were stimulated with the CB1 cannabinoid receptor agonist with HU210 for multiple time points (2h,4h,6h and 8h), followed by RNA-seq to identify HU2010 triggered differentially expressed genes. The up regulated genes were subjected to Gene Ontology enrichment analysis to predict up regulated sub cellular processes that they belong to. Among the inferred subcellular processes are vesicular transport, microtubule organization and elongation and membrane lipid metabolism.
Based on these inferences, we built a dynamical multicompartment ODE model that integrates models of membrane production at the cell body, membrane delivery to the axonal tip via microtubule based vesicular transport and axonal microtubule growth. We predicted that such a large-scale model should simulate neurite-outgrowth and CB1 receptor stimulation of the processes. We find that we are able to simulate neurite outgrowth using the subcellular processes identified from the mRNA-Seq experiments and incorporating changes in the levels of proteins encoded by upregulated genes leads to significant increases in the rate of neurite outgrowth. Details of the simulations will be presented.