Novel Drug Targets And Reporter Systems

We are searching for novel repair-mediating drug targets from various cell types of the diseased brain with unbiased methods. By implementing RNA sequencing, proteomics, and metabolomics we can find new molecules involved in regenerative processes in various brain cell types.

In addition, we are interested in neurotrophic factors, their signalling and role in the progression of diseases. Our work is highly focused on CDNF (cerebral dopamine neurotrophic factor) and MANF (mesencephalic astrocyte-derived neurotrophic factor) and their molecular and cellular effects. However, genes that are transcribed from the antisense strand of DNA and located opposite to neurotrophic factor genes are also being explored by us. Namely, we are studying glial cell line-derived neurotrophic factor opposite strand (GDNFOS, Airavaara et al., 2011, J BiolCHem). Intriguingly, GDNFOS-3, one of the three GDNFOS transcripts, is a potentially protein-coding gene only in human, chimp and rhesus monkey.

After drug target validation we establish reporter assays for novel drug targets to find novel small molecule ligands. The reporter assays are based on epifluorescence, luciferase or tocolorimetric reactions. We are implementing CRISPR/Cas9 genome editing technology, lentiviral vectors and adeno-associated virus (AAV)-vectors in our studies