Advanced (epi)genomics

Novel drug targets potentially involved in vulnerability and resilience to disease are being identified by combining animal models for disease with expression profiling analysis in brain nuclei obtained by laser microdissection (LMD). In addition, we analyze the extent to which the DNA of genes involved in resilience to disease is accessible for regulating factors. For this we use whole genome chromatin immunoprecipitation, and analysis of epigenetic DNA modulation by methylation throughpyrosequencing.

We are presently working on identification of targets in psychosis, based on our micro-array mRNA analysis of three different brain areas that play pivotal roles in the brain circuits involved in the responses to psychostimulants (collaboration Lundbeck, Denmark). In other projects experimental type 1 diabetes and also exposure to chronic stressors were identified as conditions in which the transcriptional response to acute glucocorticoidsare compromised in hippocampus, suggesting a decrease in hippocampal resilience (collaboration BS McEwen, Rockefeller U, NY& M Joels, Uinv of Amsterdam). In a HFSP project, we are evaluating the impact of early life stressors on the responsiveness to glucocorticoids in adult life, using the so called ChIP-seq technique, which allows genome wide analysis of genomic target availability for the adaptive glucocorticoid signal (collaboration with the LCTG).