Primary fields of research
I have a mechanistic interest into genome-wide and locus specific regulation and fine-tuning of tissue-specific gene expression. We are interested in the 3D-organization of genome within the nuclear space, non-coding RNAs and epigenetic modifications especially methylation and hydroxymethylation. The interaction of these linear and 3-dimentional mechanisms in gene regulation within the healthy brain and the neurodegenerative diseases is the primary interest.
For a very long time we have been working on a specific familial balanced translocation t(8;20) segregating with early onset cerebellar ataxi and use this translocation in learning about the organization and the function of the genome around the breakpoints. The synapse associated DLGAP4 gene which spans one of the breakpoints became my favorite gene over the years.
I do not like being limited by the technical short-comings when I need to find answers to biological questions. Therefore, I have a great interest in developing novel methods based on in situ hybridization both at RNA and DNA level, and I try novel probe technologies and develop new nuclear preparation methods in order to study the genome organization by pushing the resolution limits from different sides . We think multidiciplinary projects are always exciting. Over the years, we have been collaborating with DTU Nanotech in developing lab-on-a-chip devices for genetic analyses.
- Is distrupted genomic architecture the cause or the effect in the neurodegenerative diseases? The organization of the genome in territories, domains and loops is essential for normal development and function. This non-random organization provides a new layer of fine transcriptional regulation especially in the brain. The role of spatial genome organization in normal and diseased brain cells is being investigated and it is suggested as a potential tool for presymptomatic diagnosis in neurodegenerative diseases.
- Using a balanced translocation t(8;20) segregating with Early Onset Cerebellar ataxia, we have found DLGAP4 gene at one breakpoint as the candidate for the ataxia phenotype. We are characterizing the function of DLGAP4 and some of the novel non-coding RNAs found in the vicinity of the breakpoints.
- Developing tools for high resolution visual analysis of the genome has always been a great interest. We are working on chromatin spreading techniques in collaboration with Niels Tommerup as well as collaborating with Jesper Wengel, SDU on locked nucleic acid based new probe technologies for possibilities of hybridization without the need for denaturation which is suggested to change the genomic architecture.
- In collaboration with DTU Nanotech, we are developing a work flow for sequencing of long DNA molecules as a supplementary method for next generation sequencing. The method is based on obtaining megabase-sized single DNA Molecules from a specific region of the genome for optical mapping in a nanofluidic device.