What Although disentangling the effects of demography vs natural selection is a critical prerequisite for understanding patterns of diversity in disease-associated genes, we have been limited to the use of theory and/or extrapolation from observations on contemporary population diversity, when attempting to understand the impact pathogen pandemics had on the human gene pool. Today an alternative approach is possible - directly observing the genomic consequences of these catastrophes through genome scale analysis of historic human specimens. This project will leverage on the power of population palaeogenomics in the context of historical, archaeological, and medical genomic information, to explore the consequences of the second plague pandemic on Northern Europe's populations. Why Human palaeogenomic studies have principally focussed on reconstructing human migration history. In contrast, this project represents one of the first applications of ancient population genomic data to directly characterize how selection has shaped the whole genome. As such, we hope that our study will act as a beacon that showcases the use of palaeogenomic data as a powerful new tool with which to better understand how selection has shaped modern genetic variation – something relevant to both the basic and applied (medical genetic) research communities. Furthermore if we find any evidence for genetic variants that conferred resistance to the plague, these may be of future medical interest. How We will generate population scale genomic, epigenomic and bacterial metagenomic data using the extensive skeletal records at 9 Northern European locations. The samples studied are chosen specifically to date to either before, or after the plague pandemic, and we will also generate modern control reference data from each location. The data generated will be analysed using population genomic techniques, to both explore how the pandemic affected population movement into the cities through time, but also for any signals that certain genetic variants conferred resistance to the plague. SSR Europe's human skeletal archives hold enormous potential for improving our understanding of the past. Given their incalculable value, we are ethically bound to maximise the knowledge gained from them, while minimising destruction to this invaluable resource. Through the methods developed during this project, and by showcasing how genomic data from such samples can be used to study questions relating not only to human migration history, but questions of direct medical relevance, we will be meeting this need.