Project description:Pilot study on leaves from Papua New Guinea showing soil toxicity, extracted in RNAlater in one case and MQ water in another, also MQ blanks
Project description:SARS-CoV-2 has caused the largest known coronavirus pandemic and is believed to have emerged from insectivorous bats. Little is known about the evolution of these viruses in their reservoir bat species. In this study, we investigated SARS-CoV-2-host interaction using human and bat cells. Bat cells mount a robust and early antiviral response but elicit a dampened pro-inflammatory response upon SARS-CoV-2 infection compared to human cells. Furthermore, an inactivating R685P mutation within the furin cleavage site (FCS) of the SARS-CoV-2 spike protein was naturally selected for in infected bat cells. Taken together, our data demonstrate that insectivorous bat cells have evolved a differential antiviral immune response against SARS-CoV-2 infection, likely to mitigate immunopathology that is observed in humans. Our study sheds light on the evolution of sarbecoviruses in bats and extends molecular evidence to data from field studies that have demonstrated that SARS-CoV-2-related viruses in wild-caught bats lack an intact FCS.
Project description:Bats can harbor many pathogens without showing disease. However, the mechanisms by which bats resolve these infections or limit pathology remain unclear. To illuminate the bat immune response to coronaviruses, viruses with high public health significance, we will use serum proteomics to assess broad differences in immune proteins of uninfected and infected vampire bats (Desmodus rotundus). In contrast to global profiling techniques of blood such as transcriptomics, proteomics provides a unique perspective into immunology, as the serum proteome includes proteins from not only blood but also those secreted from proximal tissues. Here, we expand our recent work on the serum proteome of wild vampire bats (Desmodus rotundus) to better understand CoV pathogenesis. Across 19 bats sampled in 2019 in northern Belize with available sera, we detected CoVs in oral or rectal swabs from four individuals. We used data independent acquisition-based mass spectrometry to profile and compare the undepleted serum proteome of these 19 bats. These results will provide much needed insight into changes in the bat serum proteome in response to coronavirus infection.
Project description:Bats are remarkably long-lived for their size with many species living more than 20-40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigated requirements for malignant transformation in primary bat fibroblasts in four bat species - little brown bat (Myotis lucifugus), big brown bat (Eptesicus fuscus), cave nectar bat (Eonycteris spelaea) and Jamaican fruit bat (Artibeus jamaicensis) – spanning the bat evolutionary tree and including the longest-lived genera. We show that bat fibroblasts do not undergo replicative senescence and express active telomerase. Bat cells displayed attenuated stress induced premature senescence with a dampened secretory phenotype. Unexpectedly, we discovered that bat cells could be readily transformed by only two oncogenic perturbations or “hits”: inactivation of either p53 or pRb and activation of oncogenic RASV12. This was surprising because other long-lived mammalian species require up to five hits for malignant transformation. Additionally, bat fibroblasts exhibited increased p53 and MDM2 transcript levels, and elevated p53-dependent apoptosis. The little brown bat showed a genomic duplication of the p53 gene. We hypothesize that bats evolved enhanced p53 activity through gene duplications and transcriptional upregulation as an additional anti-cancer strategy, similar to elephants. In summary, active telomerase and the small number of oncogenic hits sufficient to malignantly transform bat cells suggest that in vivo bats rely heavily on non-cell autonomous mechanisms of tumor suppression.