Tracking virus-induced shifts in cellular ultrastructure: Developing novel 3D correlative imaging pipelines to anticipate and track the effect of viral infections within living cells

About the Project

Ultrastructural analysis of mammalian cells gives important insights into cellular physiology and, most interestingly, cellular heterogeneity.

This project will be part of the recently awarded NanoX ERC Synergy grant with the goal to develop diagnostic capabilities using micron-sized biopsies to assess ultrastructural cellular features. The project will make use of an automated imaging pipeline for correlative ultra-high resolution 3D imaging of mammalian cells developed for the beamline B24 at the UK synchrotron Diamond Light Source to study influenza infection in standardised model cell lines.

We will ask why only some cells in a population get infected by viruses and how cellular features restructure throughout an infection. The spatial resolution across scales will enable to neighbouring cells change their ultrastructure in response to their neighbours’ state of health. Moreover, given that a known factor influencing cellular heterogeneity and infection of cells by viruses is the cell-autonomous circadian clock, we can also map circadian phase variation in ultrastructure to viral infection potency and persistence.

Understanding the effect of infection on cellular ultrastructure will lead to physiologically relevant insights into the life of a prominent human pathogen

This project will bring together ultra-high resolution correlative optical and soft X-ray imaging with infection cell biology and circadian biology based on the background of the supervisors.

The student will combine in vitro experiments (tissue culture and viral infection/propagation), cryo-imaging, advanced 2D and 3D image analysis and circadian paradigms to identify ultrastructural correlates of cellular health and susceptibility to infection.

Further methods will include viral infection and viral quantification assays (e.g., qRT-PCR, plaque assays), fluorescence microscopy, general molecular biology and microbiology techniques.