Research & Projects

In addition to diffusive signals, cells in tissue also communicate via long, thin cellular protrusions, such as airinemes in zebrafish. Before establishing communication, cellular protrusions must find their target cell. In this project, we demonstrate that the shapes of airinemes in zebrafish are consistent with a finite persistent random walk model. The probability of contacting the target cell is maximized for a balance between ballistic search (straight) and diffusive search (highly curved, random). We find that the curvature of airinemes in zebrafish, extracted from live-cell microscopy, is approximately the same value as the optimum in the simple persistent random walk model. We also explore the ability of the target cell to infer direction of the airineme’s source, finding that there is a theoretical trade-off between search optimality and directional information. This provides a framework to characterize the shape, and performance objectives, of non-canonical cellular protrusions in general.

https://doi.org/10.7554/eLife.75690

Many signaling cascades involve dynamic relocalization of signaling molecules at the primary cilium. Mislocalization of signaling molecules is associated with a class of diseases called ciliopathies. Numerous studies have been focusing on identifying different molecular factors which affect the distribution of signaling molecules in the primary cilium; however, even for the most well studied pathway, such as Hedgehog signaling pathway, the mechanism which selectively controls the localization of signaling molecules is still debated. Furthermore, there is much prior evidence for a diffusive barrier at the base of the cilium, but 'diffusive barrier' can mean several distinct biophysical phenomena, e.g., a mechanical barrier or an increase in local viscosity. 

In this project, we propose a primary cilium signaling molecule transport model with consideration of different molecular and biophysical factors which are hypothesized to be important for its coordinated transport and selectivity. With this model, we predict the distribution of signaling molecules upon various perturbations of biophysical factors. We further develop a method which uses single particle tracks to distinguish local changes in viscosity versus local elastic barriers. Moreover, our method can distinguish how much of the movement is due to membrane heterogeneity versus cytoplasmic (or cilioplasmic) structures. This method is based on advances in Bayesian statistical learning to detect subtle differences between biophysical forces which are difficult to be experimentally identified. 

Expansion microscopy is a technology which enables the acquisition of high-resolution images by physically expanding biological samples using a swellable hydrogel. I have been working on development of a new type of expansion microscopy, and I am currently finalizing the manuscript submission to peer reviewed journal. I will provide more detailed information about the project, and update the image soon. In the meantime, I have used expansion microscopy to obtain the above image, which shows the structures of microtubules (green) and clathrin coated pits (magenta) in high resolution (~30nm resolution).