Brandon Invergo

Exploring the rate-limiting steps in visual phototransduction recovery by bottom-up kinetic modeling

Recently we published an article in Cell Communication and Signaling entitled "Exploring the rate-limiting steps in visual phototransduction recovery by bottom-up kinetic modeling". This work was done in collaboration with Dr. Daniele Dell'Orco from the University of Verona and Dr. Karl-Wilhelm Koch of the University of Oldenburg, who graciously hosted me in his lab for 3 months at the end of 2011.

In this article, we extended and improved a dynamic model of the visual phototransduction pathway originally implemented by Dr. Dell'Orco. Most notably, we replaced a somewhat wonky description of the interaction between the protein Rhodopsin Kinase and Recoverin, a protein that regulates its activity. The new representation is much more realistic and clear and is based on the latest biochemical knowledge. We further extended the model with a dynamic homo-oligomerization mechanism of the protein Arrestin.

We used this updated model to explore the dynamics of the recovery mechanisms of a phototrasduction response. We did this by recapitulating several experiments, showing that the model could accurately predict the majority of different mutant states previously generated in the lab. We also took advantage of the unique ability to model the states of specific proteins over time during a response, in particular to find that Arrestin oligomerization plays a role in delaying the availability of its monomeric form for shutting down Rhodopsin. And all of this was done without having to generate and experiment on any mutant animals!

The article is open-access, so you do not have to have access to a fancy university library to check it out, so have at it!

(Note: at the time of writing, only a provisional PDF is available. This file contains some typographical errors of which we are already aware. You may want to check back after they make available the final format)