User:Ty M. Thomson

Thesis Topic

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).

1. 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.
2. 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.
3. 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.
4. 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.