Maiken Søndergaard Kristiansen
I did my PhD at Aarhus University in Denmark under the supervision of Professor Torben Heick Jensen, studying interaction partners of the human RNA exosome. After finishing my PhD I worked as a postdoctoral researcher in the laboratory of Dr Natalia Gromak at the University of Oxford studying R-loop interacting proteins. After this, I joined the laboratory of Professor Catherine Porcher and her team to study blood development.
My research in the Porcher group focuses on the molecular mechanisms underlying embryonic blood development, and particularly on the function of the proto-oncogene SCL/TAL1, a regulator at the apex of the haematopoietic transcriptional hierarchy. Unravelling SCL's function is essential for a better understanding of how haematopoietic stem cells (HSCs) are formed during embryonic development.
Whilst SCL's key target genes in this process are now identified, very little is known about the multiprotein complexes that direct their timely transcriptional regulation. Importantly, SCL plays both activating and repressive functions. This strongly suggests that distinct SCL-containing multi-protein sub-complexes exist that contain either activators or repressors. The main aim of my work is to identify SCL's protein interaction partners in blood-fated mesodermal cells to help us understand SCL's dual role, ie specification of blood cells and repression of alternative lineages. This work is performed by affinity purification of SCL-containing complexes followed by mass spectrometry analysis.
In the course of these studies, I use CRISPR-Cas9 to create genomic-engineered cell lines, which enable me to easily make reporter cell lines, knockout models and mutants to help further understand the functions of SCL.
Finally, I also explore the emergence of lineage-fated cells by using highly sensitive single molecule RNA Fluorescent In Situ Hybridisation (FISH) microscopy. With this technique, I can follow the co-expression of single mRNA molecules affiliated to distinct lineages, in single cells and at different stages of development. This allows me to investigate if and at what stage multi-lineage primed cells emerge and to document lineage bi-furcation towards uni-potency.
SCL/TAL1: a multifaceted regulator from blood development to disease.
Porcher C. et al, (2017), Blood, 129, 2051 - 2060
The human cap-binding complex is functionally connected to the nuclear RNA exosome
Andersen PR. et al, (2013), Nature Structural and Molecular Biology, 20, 1367 - 1376
Interaction Profiling Identifies the Human Nuclear Exosome Targeting Complex
Lubas M. et al, (2011), Mol Cell, 43, 624 - 637
The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L
Tomecki R. et al, (2010), The EMBO Journal, 29, 2342 - 2357