Dr Katharina Scherer

Determinants of efficient assembly to optimise LAIV vaccines

AstraZeneca’s FluMist which is a live attenuated influenza vaccine (LAIV) must be optimised every year due to the mutations in the influenza strains. However, to date it cannot be well predicted how the introduced changes in the vaccine affect its efficacy.

We work together with AstraZeneca to find the molecular interactions that determine when LAIV assembly is efficient. Effective assembly has been shown to be a requirement for a good vaccine in previous studies. We compare LAIV strains that are representatives of good and bad vaccines with known differences in their genome. In order to probe for differences in gene segment interactions - one known important driver for virus particle assembly -, we employ RNA FISH in combination with expansion microscopy for 4x increased spatial precision. By specifically labelling the eight different genes of the virus with fluorescent probes, we also screen for variation in gene expression and transport kinetics in the different strains.

Dynamics of SARS-CoV-2 infection using pseudotemporal single cell mapping

Despite being the target of extensive research efforts due to the COVID-19 pandemic, relatively little was known about the dynamics of SARS-CoV-2 replication within cells. We have investigated and characterised the tightly orchestrated sequence of events during replication. Our data provide new insights into the spatiotemporal regulation of SARS-CoV-2 assembly and refine current understanding of SARS-CoV-2 replication. Our study has recently been accepted in Science Advances.

As I have previously shown for herpes simplex virus 1 (HSV-1), viral protein expression patterns can serve as an intrinsic timestamp. We used this inherent property for single cell-based classification and pseudotemporal mapping of host cell remodelling and SARS-CoV-2 assembly. Since a high degree of cell-to-cell variability in infection is expected and has been observed for a range of mammalian viruses, such a single cell-based analysis is more informative than the population average.

Mechanism of HSV-1 envelopment

Herpesviruses are widespread human pathogens that establish life-long latent infections. In collaboration with Dr Colin Crump, I investigate the molecular mechanisms of the final step of herpes simplex virus 1 (HSV-1) assembly, the envelopment of capsid and tegument into the membrane envelope. Little is known about the dynamics of this process and the roles of different viral proteins are still unresolved. We hypothesise that genetically engineered mutants of viruses that have defective or delayed secondary envelopment exhibit very distinct mobility patterns compared to the wildtype. By recording videos with fast acquisition rate, we perform a motion analysis by tracking single viral particles.