Andreas Moor, Prof. Dr., Simona Baghai, Costanza Borrelli, Kristina Handler, Atefeh Lafzi, Dr., Jonas Kretz, Martin Mikl, Dr., Laura de Vargas Roditi, Dr., Christiane König, Karelia Vélez
Our research focusses on exploring the way in which single cells collaborate within tissues to achieve their common functions. A thorough comprehension of these tissue components is crucial for advancing our knowledge of normal homeostasis and pathophysiology; disrupted cellular interactions can lead to decreased tissue function or even carcinogenesis.
Collaboration happens not only across historically defined cell types, there is also significant heterogeneity within cell types and even within cytoplasmic compartments of polar single cells. We are making use of quantitative approaches to study cellular and subcellular heterogeneity while preserving information about the spatial tissue context.
Spatial division of labor in the murine intestinal epithelium. Blue Ada mRNA, Red Slc2a2 mRNA, green Reg1 mRNA.
Cellular interactions in cancer
Tumors are not a homogenous mass of cells but consist of heterogeneous tumor cell types, invading immune cells and connective tissue. The last years have brought promising therapies that act on infiltrating immune cells in tumors. However, we are still lacking a detailed understanding of all the interactions that occur among different individual cells within a tumor. Conventional analysis methods of bulk samples are blind to cellular heterogeneity and spatial tumor information, which is a major obstacle in the field.
We are addressing this gap by combining single cell genomics and single molecule RNA imaging to study spatial single cell heterogeneity in cancer pathophysiology. Our approach will yield a colon cancer single cell atlas that characterizes the molecular state and the corresponding spatial location of all the heterogeneous tumor and stromal cells. This will uncover novel pathways that mediate intra-tumor interactions. We will then target these potential weak spots to assess their therapeutic potential in functional studies in cancer organoids.
We develop novel methods to analyze how spatial position is related to function in homeostasis and pathophysiology. We are interested in such relationships across different biological scales: how is the position of an intracellular organelle related to its function within the cell? If we zoom out, how is the location of a cell within a tissue determining its microenvironment and do cells at different locations perform differing tasks for the tissue?
Intracellular mRNA localization
In previous work we have assessed the whole transcriptome of a mammalian epithelium in regard to subcellular RNA distribution. Our study revealed a novel layer of spatial gene regulation through localized translation in mammalian epithelia and opened many interesting research questions. It is still unclear how this large-scale RNA localization is achieved in a sequence-specific manner and if it is involved in intestinal pathophysiology. The abundance of localized transcripts in the intestinal epithelium and their dynamic adaptation in physiology imply localization as a tightly regulated process. We aim to understand how this regulation occurs in a transcript-specific manner, if it enables this tissue to perform its tasks more efficiently and if the disruption of localization patterns can be causally linked to cellular phenotypes.
Intracellular mRNA localization in the intestinal epithelium. Red: Apob mRNA, green: Net1 mRNA, blue: DAPI.