Our group is exploring several research lines to address fundamental questions in RNA biology. Many of the concrete ongoing projects center around microRNAs and gene regulation in single cells – for instance studying alternative microRNA functions in regulating gene expression variation (noise) and covariation (synchronicity). Besides the concrete ongoing projects listed here, we engage in collaborations where we can in particular apply our expertise in advanced transcriptomics and custom sequence analyses.
Paleotranscriptomics

Today, sequencing of DNA from ancient samples is a standard method in Paleogenomics, however, RNA is generally unstable due to the ubiquitous presence of RNases in the environment. In collaboration with Love Dalén (Center for Palaeogenetics) and Tom Gilbert (Centre for Evolutionary Hologenomics) we have recently shown that RNA can be detected and sequenced from ancient canid samples >14,000 years old, and we provide evidence for the authenticity of these samples in three different ways. First, some of the sequences originate from canid-specific microRNAs, that never evolved in other species. Second, the sequences display characteristic damage patterns of ancient nucleic acids. Third, the transcriptome profiles of the ancient samples resemble those of corresponding modern tissues – for instance ancient canid liver resembles modern dog liver. We are now sequencing more ancient samples, with the purpose of discovering new species-specific microRNAs that may give insights into the physiology, adaption and extinction of ancient megafauna. In a parallel research line, we also study RNA from recently extinct animal species such as the Thylacine (Tasmanian tiger).
Argonaute TRIBE
Antibody-based methods such as CLIP can detect direct interactions between microRNAs and their mRNA targets in cell populations with nucleotide resolution. However, these methods typically require millions of cells, and cannot be applied to study the single cells where the interactions occur. We have developed a new method to detect microRNA targeting in single cells using the so-called TRIBE approach, where an RNA-binding protein of interest is fused to an editing-capable protein domain. In effect, Argonaute-loaded microRNAs guide the fusion protein to its targets, and the editing domain leaves irreversible marks that can be detected using single-cell RNA sequencing. We foresee that Argonaute TRIBE will be useful to the wider research community – both as a new single-cell method, but also as a bulk method that circumvents the need for laborious immunoprecipitation and high-quality antibodies.
SPARC-seq
Currently there exist methods to profile the entire transcriptome along with either surface proteins (CITE-seq) or nuclear proteins (inCITE-seq) in single cells. We are expanding a method (SPARC-seq, developed by Caroline Gallant) to profile the entire transcriptome along with cellular proteins of any localization, in single cells. We will apply this method to unresolved questions in the microRNA field – for instance if any microRNA biogenesis or effector proteins constitute bottle-necks in microRNA function, or how microRNAs affect the expression variation and covariation of their targets at the transcriptome and proteome level.
Gene expression covariances
We have previously studied gene expression covariances in single cells, and found that thousands of gene pairs appear to be carefully synchronized (Tarbier et al., 2020). These covariances appear to be induced by regulators such as transcription factors and microRNAs, and can function to ensure stoichiometry between proteins that are part of the same complex. We are further exploring the roles of microRNAs in regulating gene expression variation and covariation, and we are also investigating covariation patterns to find new regulatory relationships. For instance, we find that the Malat1 long non-coding RNA covaries with many mRNAs, and we find evidence in orthogonal Omics data that Malat1 is indeed regulating these genes.