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HEIndividual fellowship2023–2025

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

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-09-01 → 2025-08-31
EU contribution
€173,847
Participants
3
Scheme
HORIZON-TMA-MSCA-PF-EF

Lines connect the coordinator with its partners.

Results in brief

Revealing the gene regulatory networks that govern cell mechanical properties by single cell microfluidics

Our bodies are formed of microscopic cells, which underpin all our bodily functions, from white blood cells which recognise and destroy pathogens, to muscle cells which enable movement and brain cells which store memories. One of the central aims of biology is therefore to understand how cells achieve their numerous functions. However, cells are incredibly complex, and even individual cells within populations exhibit significant heterogenity, rendering this endeavour extremely challenging. In order to address these challenges and disentangle cellular function, we need to study large numbers of individual cells in high detail. Recent technology advances mean that we now have a plethora of methods for studying the molecular components of cells, at the single cell level. For example, for each cell, we can determine gene sequences and their corresponding expression levels. We are also able to rapidly profile single cell behaviour and physical properties, such as their size, shape, and mechanical stiffness. However, the link between the molecular composition and the physical, functional properties of cells remains heavily underexplored, due to a lack of suitable methods. This project therefore aimed to establish new technology which simultaneously profiles both the physical properties and molecular components of individual cells in high-throughput. This will allow us to understand how molecular composition determines physical properties, such as identifying genes which regulate cell size and mechanical stiffness. This technology can then be used in a range of scientific areas, from understanding the fundamental processes behind embryo development to probing mechanisms of cancer pathology.

Data: CORDIS, © European Union

Project objective

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.

Original text from CORDIS.

Participants

  • MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV · MUNCHENCoordinatorGermany
  • EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH · ZuerichSwitzerland
  • UNIVERSITY OF WASHINGTON · Seattle WaUnited States

Links

Data: CORDIS, © European Union