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Anthropology Professor, Hendrik Poinar

Anthropology Professor, Hendrik Poinar, is a recipient of the New Frontiers in Research Fund - Exploration 2019 Grant

The grant is for Poinar's research, which is called Ancient memory: "Reconstructing the antibody repertoires of ancient humans to probe infectious diseases of the past"

Apr 27, 2021

Infectious diseases have exacted high morbidity and mortality on humans throughout history and continue to do so today in a disproportionate manner for those of lower socioeconomic status and with insufficient access to health care and proper sanitation.

A better and perhaps more nuanced comprehension of the tightly linked association between infectious disease and the human condition helps us better contextualize the emergence (and re-emergence) of pathogens in the past as well as today.  We have been attempting to chronicle the types of infectious agents in the past to address questions about disease burden, during well-known pandemics (i.e Black Death), but also as a consequence of transitions, such as the adoption of agriculture (the Neolithic transition). Unfortunately, most infectious diseases with acute onset, like the plague, don’t leave diagnostic lesions in bones but can, in a few rare cases, leave their DNA. However, it is likely that chronic and enteric (i.e. non-acute) infections –such as dysentery –which leave neither were the predominant causes of morbidity and mortality in the past. Finally, many viruses carry RNA genomes, which precludes preservation in ancient samples. Therefore, we underestimate the relative frequency of disease, leaving many unresolved questions about syndemic processes and disease origins.

A possible solution is to look at the human “memory” response to an infection via the antibody repertoire. Bone marrow is an important niche for antibody-producing cells that have been generated by prior infections. B cell antibodies that are good ‘fits’ to a particular antigen are recombined, amplified, and hypermutated and thus the sequence of the B-cell VDJ chains can be linked to the antigen from a particular pathogen. By sequencing the repertoire of an individual’s antibodies, we gain access to the history of infection over the course of their life span. Sequences from these repertoires can be used to synthesize the antibody in vitro, which can then be screened against a broad array of pathogen antigens (>100) to link the antibody to the pathogen.

We plan to use ancient DNA from bones and teeth of victims of pandemics (6th-18th C), to enrich for B-cell VDJ combinations, sequence, and bioinformatically reconstruct them, guiding the in-vitro synthesis of ‘ancient’ antibodies. By leveraging the immunological “memory” of ancient humans, our novel approach holds the promise of transforming our understanding of infectious disease burdens of the past.

This research summary is taken from the New Frontiers in Research Fund

Read more about the other recipients of the Fund.