Research 

Dynamics of nuclear signaling

A-kinase anchoring proteins (AKAPs) target the cAMP-dependent protein kinase (PKA) and other signaling molecules to  various subcellular loci for maximum enzyme efficacy. After establishing a role for AKAP149 in RNA binding at mitochondrias, we are focussing on AKAP95's involvement in nuclear signalling. We also study the  Protein Phosphatase 1 (PP1) nuclear targeting subunit PNUTS, which we have newly shown to be a component of the DNA damage response involved in DNA repair.

Figure: Immunofluorescence analysis of AKAP149 (red) in HeLa cells transfected with the mitochondria marker DMDDX28. 

Video - Laser scanning confocal analysis of HeLa cell nuclei showing recruitment of PNUTS (red) to double strand breaks in DNA before recruitment of 53BP1 (green) (O.J.B. Landsverk and O. Bakke).


Nuclear reprogramming

The mechanisms underlying genomic plasticity are poorly understood. Alteration of cell fate involves a reprogramming of nuclear function. Using cellular extract-based approaches, we are exploring the transdifferentiation and dedifferentiation capacities of somatic cells.

Figure: Epithelial 293T cells reprogrammed into embryonic stem-like cells using extract from pluripotent cells.


 

Epigenetics of mesenchymal stem cells

The stromal compartment of mesenchymal tissues harbors multipotent stem or progenitor cells that display proliferative capacity in culture, and multilineage differentiation potential. A recent research axis in our lab is the characterization of the molecular processes that govern ‘stemness’ in freshly isolated and cultured stem cells purified from adipose tissue.

Figure: Adipocytes differentiated from adipose stem cells. Intracellular lipid droplets are stained with Oil Red-O.

 

Chromatin immunoprecipitation assays

Chromatin immunoprecipitation (ChIP) is a powerful technique to map the binding of post-transcriptionally modified histones, transcription factors or other proteins on DNA in the genome. We have developed fast ChIP assays suitable for very small cell numbers, which open doors to epigenetic analyses of cell and tissue samples up to now excluded from such investigations.