Research QuestionsHow do objects move inside cells and what is the correct statistical description of this transport?
How is transport in complex environments affected by the metabolic state of the cell and cell stimulation?
Are the mechanisms of transport designed by evolution to do more than just get "stuff" from here to there and if so are cells optimized for robustness or other qualities?
CRISPR-ed beta cell with expression of a fluorescent protein in insulin granules
We are studying the dynamics of insulin-containing granule transport in beta cells, both in small cell clusters and in larger “pseudoislets” to simulate the islet of Langerhans. We have produced new beta-cell types that are either poor (diabetic) or good (normal) secretors of insulin as a model. This allows us to conduct tracking experiments with a longer view to whether the diabetic disease phenotype is related to transport. Additionally, we have used CRISPR to fluorescently tag insulin to measure cell-to-cell differences in transport.
Stained microtubules and nuclei of beta cells
We have found a new statistics, which combines continuous time random walks with fractional Brownian motion, that describes the granule (vesicle) transport in these cells. We are extending these single granule particle tracking measurements to the dynamics of microtubules in vivo. This is a challenging issue from both the image analysis/tracking perspective and also establishing the correct mechanical description of their string-like motion. We apply chemical and optical perturbations to the cells to change the cell state to understand how transport, as a nonequilibrium process, is altered.