Descrizione del progetto
Conoscere la regolazione genica relativa alle proprietà meccaniche delle cellule
Le cellule interagiscono con il loro ambiente generando e sostenendo forze meccaniche. Le proprietà meccaniche delle cellule influenzano una pletora di funzioni cellulari, tra cui l’adesione, la migrazione e la polarizzazione, e sono fondamentali durante lo sviluppo e il differenziamento. Tuttavia, le reti di regolazione sottostanti responsabili del controllo delle proprietà meccaniche delle cellule rimangono in gran parte poco studiate. Il progetto READ-seq, finanziato dal programma di azioni Marie Skłodowska-Curie, si propone di risolvere questo problema sviluppando una piattaforma microfluidica che combina analisi fisiche e biochimiche delle cellule. La piattaforma misurerà simultaneamente le caratteristiche meccaniche e morfologiche delle singole cellule e le assocerà al loro profilo molecolare, fornendo un collegamento senza precedenti tra espressione genica e meccanica cellulare.
Obiettivo
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.
Campo scientifico
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-AG-UN - HORIZON Unit GrantCoordinatore
80539 Munchen
Germania