WP2 – Neural cell localization of brain disorder-relevant genes

Researchers: Elly Hol (co-leader), Jeroen Pasterkamp (co-leader), Alexander van den Oudenaarden, Guus Smit, Onur Basak.

The neural cell diversity of the brain is astonishing, and we are still discovering cell types with new function. In WP2, we aim to reveal the molecular profiles and spatial distribution of neural cells with the aim of finding cell types relevant for brain dysfunction. For this, we will

  1. Generate mRNA expression profiles of single human and rodent cells, including non-coding RNAs, spliced RNAs, as well as epigenetic profiles, including DNA modifications, DNA accessibility, and histone modifications
  2. Develop novel technologies for single cell omics and single cell protein/mRNA analyses optimized for brain research, e.g. methods for detection of multiple transcripts in situ, single cell omics approaches for RNA splicing, editing, epigenetic analysis, 3D light sheet microscopy and image analysis.
  3. Generate spatial localization maps of the different types of neural cells in the meso-cortical system and prefrontal cortex in relation to cell circuitry function and behaviour, studied in WP3 and WP4.

In the long run, our results will aid determining which neural cells, including neuronal and glial subtypes, express genes indicated by GWAS, in the human and mouse brain and to determine which transcriptomic and epigenomic changes in neural cells are relevant for brain dysfunction.