Projects

While a tissue forms, its cells constantly push and pull on each other. Young cells that have not yet chosen what to become, called progenitors, add forces of their own as they move into place. We want to know how these forces work together to build a tissue that does its job.

In the skin of frog embryos, new ciliated cells squeeze up into the outer layer and feel how stiff it is with thin, finger-like protrusions. We film this in living embryos and measure the forces with open-source tools that read them from the shapes of the cells.

A mucociliary epithelium is a tissue like the lining of our airways: a carpet of cells that make mucus and cells that sweep it away with cilia. As it develops, it is stretched and squeezed by the growing body around it.

We ask whether such forces change what young cells become, and whether timing matters: the same push or pull may do nothing at one stage of development and redirect cells at another. To find out, we stretch or compress the developing tissue at chosen moments and follow which cells it produces.

Each new cell in a developing airway lining becomes one of a few types, such as cells that grow cilia and cells that make mucus. Two kinds of data describe how. Movies show how every cell changes shape and moves. Single-cell RNA sequencing (scRNAseq) reads which genes each cell is using.

We combine the two into one model of how cells choose their fate. Our movies already show that the way a cell changes shape predicts which type it will become, and our sequencing of frog skin shows that the cell types emerge gradually from shared early cells, not down a fixed family tree.

Organoids are small three-dimensional tissues grown in the lab. From tiny samples of airway tissue donated by patients, we grow organoids with the same carpet of ciliated and mucus-making cells that lines our lungs.

They let us study respiratory diseases such as asthma in human tissue, and test there what we learn in the frog.