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.
Project description:An Infinium microarray platform (GPL28271, HorvathMammalMethylChip40) was used to generate DNA methylation data from several tissues in several bat species. Tissues: skin (wing punches), liver, brain, skeletal muscle.
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:Jamaican fruit bats (Artibeus jamaicensis) naturally harbor a wide range of viruses of human relevance. These infections are typically mild in bats, suggesting unique features of their immune system. To better understand the immune response to viral infections in bats, we infected Jamaican fruit bats with the bat-derived influenza A virus H18N11. Using comparative single-cell RNA sequencing, we generated a single-cell atlas of the Jamaican fruit bat intestine and mesentery, the target organs of infection. Gene expression profiling showed that H18N11 infection resulted in a moderate induction of interferon-stimulated genes and transcriptional activation of immune cells. H18N11 infection was prominent in various leukocytes, including macrophages, B cells, and NK/T cells. Confirming these findings, human leukocytes, particularly macrophages, were also susceptible to H18N11, highlighting the zoonotic potential of this virus. Our study provides insight into the virus-host relationship and thus serves as a fundamental resource for further characterization of bat immunology.
Project description:Denmark has an extraordinarily large and well-preserved collection of archaeological skin garments found in peat bogs, dated to approximately 920 BC - AD 775. These objects provide not only the possibility to study prehistoric skin costume and technologies, but also to investigate the animal species used for production of skin garments. Until recently, species identification of archaeological skin was mainly performed by light and scanning electron microscopy or analysis of ancient DNA. However, the efficacy of these methods can be limited due to the harsh, mostly acidic environment of peat bogs leading to morphological and molecular degradation within the samples. We compared species assignment results of twelve archaeological skin samples from Danish bogs using Mass Spectrometry (MS)-based peptide sequencing, against results obtained using light and scanning electron microscopy
Project description:Fur is known from contemporary written sources to have been a key commodity in the Viking Age. Nevertheless, the fur trade has been notoriously difficult to study archaeologically as fur rarely survives in the archaeological record. In Denmark, fur finds are rare and fur in clothing has been limited to a few reports and not recorded systematically. We were therefore given access to fur from six Danish high status graves dated to the Viking Age. The fur was analysed by aDNA and palaeoproteomics methods to identify the species of origin in order to explore the Viking Age fur trade. Endogenous aDNA was not recovered, but fur proteins (keratins) were analysed by MALDI-TOF and LC-MS/MS. We show that Viking Age skin clothing were often composites of several species, showing highly developed manufacturing and material knowledge. For example, fur was produced from wild animals while leather was made of domesticates. Several examples of beaver fur were identified, a species which is not native to Denmark, and therefore indicative of trade. We argue that beaver fur was a luxury commodity, limited to the elite and worn as an easily recognisable indicator of social status.