Although it is known that the exceptional ability of bats to harbour and tolerate serious viral pathogens without experiencing severe pathological outcomes is extraordinary. Bats are recognized as important zoonotic reservoirs for emerging viral pathogens, including filoviruses (Ebola), lyssaviruses (Rabies), henipaviruses (Nipah/Hendra), and coronaviruses (SARS/MERS). The underlying mechanisms governing how bats can tolerate such harmful pathogens is hindered by limited human understanding of bat biology. Intriguingly, bats possess unique physiological adaptations, such as enhanced oxygen transport potential, altered iron homeostasis, and higher metabolic rates compared to other mammals. How cells sense and respond to variations in local oxygen tension is a fundamental pillar of cellular physiology. This response is controlled by the hypoxic-inducible-factor (HIF) signalling pathway which regulates a broad range of transcriptional targets impacting multiple levels of cellular biology to enable a cell to adapt to changing oxygen availability.
The importance and significance of carrying out this research lie in the fact that Increasing our understanding of bat biology and how this contributes to their role as a zoonotic reservoir of viral pathogens is critical for an integrated understanding of health across our ecosystem. Elucidating the molecular mechanisms underlying bat-specific adaptations in oxygen homeostasis, could have broader impacts to mammalian cellular biology. Given their unique physiological adaptations, characterising oxygen sensing in bats will result in new discoveries in hypoxia biology with broad implications to multiple disciplines beyond infection biology.
This work brings together a collection of researchers across the University of Oxford, including members of the pandemic science institute (Prof. Miles Carroll), Edinburgh University (Richard Sloan and Aaron Irving), Yale University (Craig Wilen), as well as UKHSA (Lorraine Mcelhinney and Saumya Thomas), providing critical access to bat-derived tissue from established viral surveillance programs.
The project leader, Dr. Peter Wing, said after receiving the award: “This award aims to bridge our understanding of both oxygen biology and host-pathogen interactions in a highly relevant zoonotic reservoir for serious viral pathogens. I am enormously grateful to both the BBSRC for their generous support in this endeavour and the amazing research environment at the CAMS Oxford Institute (COI) to make this research a reality.”