PhD student Dina Tekle publishes a research article in PNAS

Reconstructing EBV reactivation and DNA damage response kinetics in morphologic pseudotime

Biological Chemistry PhD student Dina Tekle, her mentor Elliott SoRelle (Microbiology and Immunology), and U-M colleagues Craig Dobry (Microbiology and Immunology) and Jonathan Sexton (Medicinal Chemistry, Internal Medicine) provide new insights into Epstein-Barr Virus (EBV) biology in research recently published in PNAS. The team used single-cell high-content screening (HCS) and morphologic pseudotime analyses to reconstruct host-virus dynamics from fixed cells. Results from their study of EBV reactivation include:

  • Differential responses to physiologic lytic stimuli and clinically relevant drugs observed
  • Quantitative morphologic metrics of treatment-dependent responses and lytic-mediated chromatin reorganization obtained
  • Spatiotemporally dysregulated DNA damage responses (DDR) identified in lytic cells via coordinated changes in nuclear structure, DNA synthesis, viral lytic proteins, and double-stranded break DDR factors

The researchers expect their approach will support high-throughput single-cell virology and be applicable to other intracellular pathogens and cellular dynamics for which live-cell imaging is challenging or technically intractable.

Research article in PNAS


diagram of experimental workflow for systematic single-cell analysis across B cell models for EBV lytic infection
Experimental workflow to characterize host ­cell responses to EBV lytic induction and progression

For more U-M Biological Chemistry news, please visit our News & Stories page. Send questions or comments to [email protected].

In This Story

headshot Dina Tekle

Dina Tekle

PhD Student, Biological Chemistry | Elliott SoRelle Lab

Elliott SoRelle

Elliott SoRelle, PhD

Assistant Professor

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