Huge leap for small molecules at the museum

Each cell of our body has the same DNA. But how do individual cells then know that they are a muscle cell, a skin cell or any other of the more than 250 different cell-types that we currently know of? Could the comparison to simpler animals, such as flatworms, with a much smaller number cell-types help to understand what goes wrong in diseases, such as cancer?

These questions are the focus of my newly established research group at the Arctic University Museum of Norway – The Fromm lab - that was funded through the Tromsø Research Foundation.

To answer these questions, we focus on really tiny molecules in animal genomes: microRNAs, because the occurrence of these important gene-regulators strongly correlates with the increasing variety of cell-types during animal evolution.

However, in order to be able to ask specific questions regarding the connection of microRNAs with distinct cell-types, a better understanding on how microRNAs are produced in cells, how many microRNAs are found in other animal groups, how they change during dramatic changes in evolution and what happens in cancer cells, was missing.

In a set of four very recent publications, that I co-authored, these four main questions were addressed.

1. The first paper led by Drs. Kang and Friedländer, previous colleagues from the SciLifeLab in Stockholm, was published in the journal Cell Reports. New insights into the cellular production of microRNAs were gained that improve our understanding of how cells can differentiate microRNAs from other RNAs. These novel insights might contribute to produce synthetic microRNAs for therapeutic approaches in the future.

2. The second paper that I led, was published in the journal Nucleic Acids Research where an international team of collaborators significantly expanded the publicly and freely available microRNA database MirGeneDB.org. The work represents an important contribution toward comparative analyses of animal evolution and the evolution of cell-types from relatively simple animals such as sponges and flatworms to more complex animals such as sharks, birds and primates, which will be the subjects of future activities in our lab.

3. Already taking advantage of the wealth of the new data in MirGeneDB, a third paper led by Dr. Peterson (Dartmouth, US), was published in the journal Molecular Biology and Evolution. The study used new insights on vertebrate chromosome evolution and not only nicely reconstructed the details of microRNA evolution in vertebrates, but also showed support for a direct link of microRNAs and animal complexity: the main assumption of our future work.

4. Addressing key question of microRNA cancer biology, co-led by Eirk Høye and conducted in the lab of Dr. Flatmark, previous colleagues from the Oslo Institute for Cancer Research, a fourth paper was published in the journal Nucleic Acids Research Cancer. Applying state of the art knowledge on cellular specificity of many microRNAs, a comprehensive framework for analysis of microRNAs in cancer, was established that also highlights previously overlooked pitfalls in microRNA research.

These four publications cover a lot of important ground for the microRNA field in general and lay the foundation for future work in The Fromm lab, which will move its focus to little studied enigmatic arctic animals, single cells and historic samples from the Museum collection. For this, we are already looking forward to welcoming our recently hired two PhD students and PostDoc at the Arctic University Museum of Norway, who will arrive in Tromsø soon.

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