Studying historic bacterial DNA

Analysis of genetic material plays a valuable role in characterising diseases. Studying genomic DNA makes it possible to detect genetic variants or epigenetic markers that constitute risk factors for certain diseases, while the study of transcripts paves the way for in-depth understanding of disease mechanisms.

Due to the degradation of nucleic acids over time in what are often suboptimal storage conditions, it can be challenging to apply the molecular pathology methods that are commonly used in clinical practice to specimens from historic tissue collections. Archaeogenetics offers a way to access and analyse historic genetic material.

The purpose of this module is to implement innovative methods for extracting nucleic acids from historic tissues, performing quality control on the extracted genetic material, and deep sequencing of DNA and RNA. We will establish proof of concept by sequencing the genome of the syphilis pathogen (Treponema pallidum) in the brains of patients who had neurosyphilis. Tissue sampling will be guided by the histopathological analysis previously carried out in WP2. The sequencing results will provide insight into the history of the bacterium based on phylogenetic analysis, and will help us investigate the emergence of factors of treatment resistance. The methods developed could then be used in future to study other diseases present in the biobank.