|
>Rename user script |
| (6 intermediate revisions by 2 users not shown) |
| Line 1: |
Line 1: |
| == Thesis Topic ==
| | #REDIRECT [[Ty Thomson]] |
| | |
| The main objectives of my work is to develop the tools to perform time-dependent stimulation and analysis of signaling pathways, and show that this is more powerful than traditional time-independent or step response analysis. I am using a computational model of the prototype system, the yeast pheromone response pathway, to generate hypotheses about the pathway. In order to test these hypotheses, time-dependent stimuli will be delivered to cells via a microfluidic device, and in vivo fluorescent reporters will be used to observe the system state. In addition to showing the strengths of this new approach to studying biological systems, I would like to use it to further our understanding of the pheromone response pathway.
| |
| | |
| == Research Goals ==
| |
| | |
| My research can be broken down into 4 main goals that follow (for the most part) chronologically).
| |
| | |
| #Build a model of the pheromone response pathway | |
| #*Develop a model of the pheromone response pathway that can be used in conjunction with time-dependent stimulation and analysis of the pathway to propose and test hypotheses. Once completed, this model can be used as a predictive tool for pathway response.
| |
| #**This model is largely already built (with instanced in Matlab and [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15637632&query_hl=1 Moleculizer]). It needs to be further refined using data from the literature, and data that I will generate myself.
| |
| #Build a microfluidic device for time-dependent stimulation of cells
| |
| #*Design, build and characterize a device to allow for rapid variation of extracellular conditions for cells fixed in a microfluidic channel.
| |
| #**This chip has been designed using the technology out of the Quake Lab at Stanford (formerly Caltech). See [[Protocols#Microfluidics| protocols]] for more info on chip design. The most recent design of the [[Stimulator]] is currently being made by the Microfluidic Foundry (Caltech). Previous instances have shown great promise for my purposes. Preliminary tests have shown that I can vary the extracellular environment (with NO cells in the channel) on a sub 100ms timescale. I've also successfully adhered cells to the bottom of the channel, and had them resist detachment under fluid flow, though this needs further characterization.
| |
| #Investigate the pathway with time-dependent stimulation
| |
| #*Examine the frequency filtering characteristics of the pheromone response pathway in order to study the limits of propagation of time-varying signals through the pathway. Use the model to form and test hypotheses generated by studying the response of the pathway to time-dependent stimulation.
| |
| #Identify and apply techniques for non-linear system identification
| |
| #*Identify and apply tools developed for other fields to the analysis of signaling pathways, particularly with respect to time-dependent stimulation.
| |
| #*Notes on [[Parameter Estimation in Matlab]]
| |
