READ-seq · Revealing the gene regulatory networks that govern cell mechanical properties by single cell microfluidics

Changes in mechanical properties of cells are key in a range of processes, including cell migration and development, and are frequently altered in disease states such as cancers. Yet, despite their key role, the gene regulatory networks underlying these processes are currently largely unresolved. Thus, the central aim of my proposed project is to gain a detailed understanding of how cellular mechanical properties are controlled, by developing microfluidic technology to simultaneously measure the mechanical phenotype and transcriptome of single cells in high throughput. The advent of single cell sequencing methods has been transformational for our understanding of biology, and multimodal approaches such as those combining genome and transcriptome measurements of the same cell, are likely to be even more so. The physical dimension, however, remains largely unexplored, and its exploitation offers the prospect of revealing how the biochemical composition of cells relates to their physical properties. I will thus apply my PhD experience to develop a microfluidic platform that combines physical and biochemical cell analysis, using real-time deformability cytometry and droplet-based single cell RNA sequencing. By matching the transcriptomic profile of each cell with its brightfield image, which yields their mechanical and morphological features, I will identify genes involved in the regulation of mechanical properties and their generality across cell types. In addition to elucidating fundamental regulators of cell mechanics, this technology will allow the investigation of their interplay with gene expression during both physiological and pathological cell state changes.