Research problem

What is the response for mRNA vaccines in mice at the single-cell level? Are there any differences in gene expression between the cell types? What is the localization and longevity of the vaccine mRNA in vivo?

Approach

The COVID-19 pandemic significantly accelerated the development of mRNA-based therapeutics. Newly generated mRNA vaccines for SARS-CoV-2 have been administered to billions of people. It is a starting point for much broader use of mRNAs therapeutics in medicine. However, our knowledge about the distribution, stability, and effects of therapeutic mRNA on the host transcriptome at the single-cell level in vivo is very limited.
Preliminary data obtained in the laboratory of Prof. Dziembowski, based on bulk analysis of RNA samples collected from experiments on animal models, strongly suggest a high variability in the stability of therapeutic mRNAs in different tissues and cell types. The cellular responses also vary. Therefore to understand the action of mRNA therapeutics and design new generations rationally, it is essential to gain a better understanding of such phenomena. The understanding of heterogeneous responses at the cellular level can be achieved due to modern single-cell analysis techniques. This project aims to set up dedicated single-cell RNA-seq protocols and apply them to analyze the cellular distribution and the effect on the transcriptome of mRNA therapeutics in vivo.