Söderbom lab

The aim of our research is to understand how non-coding (nc)RNAs regulate gene expression and how this affects evolution of multicellularity. In particular, we focus on micro (mi)RNAs, both their role in the transition from uni- to multicellular life, but also how and when miRNAs appeared during evolution. MicroRNAs are important regulators of most biological processes. These tiny 21 nt RNAs silence genes by guiding effector proteins to specific target (m)RNAs and thereby induce degradation and/or inhibit translation. However, details of their underlying mechanisms are still obscure, especially in organisms not belonging to the animal or plant linages. In our research, we use the social amoeba Dictyostelium discoideum to study functions of miRNAs during growth and development, as well as their involvement in the infectious process when pathogenic bacteria, such as Mycobacteria, attack our cells. In addition to functional studies, we are also interested in the evolution of miRNA, when and where they appeared during evolution. For our studies, we combine experimental wet-lab approaches with computational analysis.

Research

Small RNAs and their role in development and evolution of multicellularity

The main focus of our research is to understand how different biological processes are controlled by non-coding (nc)RNAs, with emphasis on gene regulation by small RNAs such as micro(mi)RNAs. For our functional studies, we mainly use the genetically tractable social amoeba Dictyostelium discoideum, a unicellular organism that upon starvation enters a multicellular developmental program where cells differentiate and communicate.

NcRNAs are RNA molecules that are not translated. Instead, they have intrinsic functions, often executed by binding to complementary (m)RNA sequences to which they guide effector proteins. This can induce cleavage, DNA/RNA modifications, translational inhibition and much more. One class of ncRNAs is miRNAs, only ~21 nt long. These small RNAs bind to mRNAs and induce cleavage and/or translational inhibition and thereby down regulate gene expression. In humans, miRNAs have been estimated to directly regulate about 60% of the genes, underscoring their importance.

One of our research aims is to better understand the biogenesis and function of miRNAs. Although miRNAs previously were believed to be unique to plants and animals, we and others have now shown that they are also present in some unicellular organisms, such as D. discoideum. In order to study the function of miRNAs, we construct knock-out strains of miRNA associated genes and investigate the effects on growth and development. We also use high throughput sequencing of small RNAs and mRNAs, using strains with different genetic backgrounds to nail down miRNA regulated target genes. We are also trying to understand the evolution of miRNAs, i.e. when and where they appeared during the course of evolution. In addition, we are interested in small RNAs involvement during infection by pathogenic bacteria, using D. discoideum as a host model. Another project is to further reveal the function of an abundant class of ~50-90 nt long ncRNAs, that we previously discovered, which seem to play a role during early development in dictyostelid social amoebae.

 

Open position:

Postdoc position in Computational biology/Bioinformatics focusing on eukaryotic RNA biology/RNA regulation/microRNAs at Uppsala University, Sweden

Group members

Research leader: Fredrik Söderbom

People

Current group members

Fredrik Söderbom, PhD
Associate professor

Bart Edelbroek, PhD student

Rooma Mansoor, PhD student

Torgny Lundberg, Master student

Group alumni

Jonas Kjellin, former PhD student
Present: Uppsala Universitet, Sanna Koskiniemi group

Zhen Liao, former PhD student

Maria Pränting, former postdoc
Present: Information Officer at ReAct

Andrea Hinas, former PhD student

Åsa Fransson, former postdoc

Lotta Avesson, former PhD student

Anders Aspegren, former Post-doc

Roshan Vaid, former research assistant

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