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:Bats as the only flying mammals incur a high metabolic cost during extended powered flight, which results in febrile-like temperatures without injury. Herein, we investigate the in vivo heat shock response (HSR) in the cave nectar bat Eonycteris spelaea. We demonstrate that E. spelaea exhibits enhanced physiological heat resistance, marked by reduced lethality, tissue damage and serum corticosterone levels in comparison to mice upon heat challenge. Additionally, E. spelaea did not exhibit an acute transcriptional response observed heat stress in mice. Instead, bats displayed a delayed and non-canonical HSR that did not involve the activation of classical heat shock related genes and pathways. This altered response in E. spelaea is attributed to the elevated basal expression of heat shock proteins, which we demonstrate to be a common characteristic exhibited by bats from diverse sub-orders, families and diets. Taken together, we demonstrate a distinct HSR in E. spelaea relative to the conventional model organism, mouse, which may provide insights to understand novel regulatory targets and effector proteins that underlie the mammalian heat shock response.
Project description:Single-cell transcriptome analysis of the in-vivo response to viral infection in the cave nectar bat Eonycteris spelaea [scRNA-seq]
Project description:Single-cell transcriptome analysis of the in-vivo response to viral infection in the cave nectar bat Eonycteris spelaea [Bulk RNA-seq]
Project description:To examine the fundamental immunity in bats, particularly the status of their innate immune system in the basal healthy state, we profile Eonycteris spelaea bat tissue with Deep NGS coverage. This is coupled to a paired experiment where bats were stimulated in vivo with various PRR ligands to activate immune pathways.
Project description:Floral nectar proteins (nectarins) are mainly enzymes and play important roles in inhibiting microbial growth in nectar and tailoring nectar chemistry before or after secretory. Nectar proteomes are usually small, but only very few plant species have had their nectar proteomes thoroughly investigated. Nectarins from Nicotiana tabacum (NT) were separated using two-dimensional gel electrophoresis, and then analyzed using mass spectrometry. Glycoproteins were isolated from raw NT nectar, separated by SDS-PAGE, and identified by mass spectrometry. All eight identified nectarins and four invertase genes’ expression were analysed by qPCR. Sugars composition, total sugar concentration, protein content, polyphenol content and hydrogen peroxide content were compared at different time intervals in extracted nectar and nectar in situ after secretion. Totally, eight nectarins were detected in NT nectar in which only two are glycoproteins, beta-xylosidase and a protein with unknown function. All of the eight nectarin genes expression was not nectary-specific and not synchronous along with the nectary development. After secretion, NT nectar in flower tube changed from sucrose–rich to hexose-rich type even though no free invertase or its activity was detected in NT nectar. No sugar composition changes observed in extracted nectar after incubating at 30 ℃ up to 48 hours in plastic tubes. Our results indicate that nectar post-secretory changes could be a complex process and tissue closely contact with nectar might function in it.