||The exploration of gene expression is necessary to understand the function of cells, organs and organisms, and it serves as basis for developing and adapting treatment strategies. The techniques currently in use rely on the homogenization of the samples, therefore the contextual information, such as localization and the associated cell types, are lost. We have been working, together with our collaborators, on an image-based method for sequencing RNA fragments in preserved cells and tissues. I will talk about this method and discuss its virtues and shortcomings. In the second part I will give some updates on our “homemade” optical projection tomography system. Besides imaging in 3D zebrafish embryos we have tested the possibility to image 3D cell cultures, which are believed to represent more accurately the living tissues and expected to have an important impact on the future drug discovery research.