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Project 2: Spatial transcriptomics - Creating a molecular map of the liver fluke F. hepatica

Most transcriptomics methods lack spatial resolution

 

Classical RNA sequencing (bulk RNAseq), in which the entire RNA from the homogenate of a tissue sample is analyzed, and the innovative single-cell RNAseq method, in which detailed information about the function of individual cells is obtained, lack information about the spatial distribution of transcripts in the sample. Spatial transcriptomics solves this problem and captures the spatial distribution of transcripts in a tissue section.

 

 

 

Spatial transcriptomics workflow

 

 

 

 

A gene expression map of the liver fluke  

 

In this project, we are mapping thousands of transcripts (mRNAs) across the body of the liver fluke Fasciola hepatica. This enables us to draw conclusions about the function of individual organs and tissues and thus contributes to a deeper understanding of the parasite’s biology. With this project, we are one of the first groups to apply the innovative "spatial transcriptomics" technology to a multicellular parasite

 

 

 

 

Spatial gene expression in liver flukes. Left: spatial transcriptomics for a transverse tissue section. Right: in situ hybridization localizing the same gene (a digestive enzyme) in the gut of the parasite.

 

 

 

 

Searching for weak points

 

Information on spatial gene expression is of particular interest when it comes to identifying new target molecules for the development of drugs and vaccines against liver flukes. Particularly promising are targets expressed in the inner and outer surfaces, which are essential for fluke survival. These include the skin-like tegument and the intestine.

 

 

 

Publication:

Gramberg S., Puckelwaldt O., Schmitt T., Lu Z., Haeberlein S. (2023) Spatial transcriptomics of a parasitic flatworm provides a molecular map of drug targets, vaccine candidates and drug resistance genes (under review), Preprint:https://doi.org/10.1101/2023.12.11.571084