Project description:Strategies that promote functional organ growth with minimal adverse effects are the ultimate goal of regenerative medicine but no single approach is currently available for organ level repair. Here, using an evolutionary adapted in vivo infection model - Mycobacterium leprae, with host cell reprogramming ability and its natural animal host, the nine-banded armadillo (Dasypus novemcinctus) that harbor bacteria in the highly regenerative liver - we present an in vivo model for promoting adult liver growth at organ level without adverse effects. Experimentally infected armadillos harboring bacteria in the liver, but not infection-resistant or drug-treated animals, showed a significantly increased total liver: body weight ratio, indicative of bacterial-driven liver organ growth in living animals. The machine-learning approach revealed an increase in healthy liver lobule number with a proportionate expansion of the hepatocyte mass with integrating vasculature and biliary networks responsible for functional liver growth. Intriguingly, infected enlarged livers show intact microarchitecture but without evidence of hepatocellular damage, fibrosis/scarring or tumorigenesis. Reactivation of armadillo liver progenitor and developmental genes/proteins, as well as upregulation of growth-, metabolism- and differentiation-associated markers with minimal change in oncogenes or tumor suppressor genes, suggests that bacteria have adapted dynamic regenerative, homeostasis and reprogramming mechanisms to promote de novo organogenesis while maintaining tissue integrity and tumor preventive strategies for host-dependent bacterial propagation. Thus, our model may facilitate the unravelling of in vivo endogenous regenerative pathways that effectively re-engage liver organ growth, with broad implications.
Project description:The project aims at unraveling the venom repertoire of the lesser banded hornet (Vespa affinis) and investigate the regimes of natural selection underpinning their venom evolution. The study also sheds light on the clinical repercussions of the V. affinis venom.
Project description:Variation in gene expression may underlie many important evolutionary traits. However, it is not known at what stage in organismal development changes in gene expression are most likely to result in changes in phenotype. One widely held belief is that changes in early development are more likely to results in changes in downstream phenotypes. In order to discover how much genetic variation for transcript level is present in natural populations, we studied zygotic gene expression in nine inbred lines of Drosophila melanogaster at two time points in development. We find abundant variation for transcript level both between lines and over time: close to half of all expressed genes show a significant line effect at either time point. We examine the contribution of maternally-loaded genes to this variation, as well as the contribution of variation in upstream genes to variation in their downstream targets in two well-studied gene regulatory networks. Finally, we estimate the dimensionality of gene expression in these two networks and find that despite large numbers of varying genesthere only appear to be two factors controlling this variation. Experiment Overall Design: Two chips for each of nine isogenic lines sampled at two time points (=36 arrays).
Project description:Natural epigenetic variation provides a source for the generation of phenotypic diversity, but to understand its contribution to phenotypic diversity, its interaction with genetic variation requires further investigation. MethylC-seq from naturally-occurring Arabidopsis accessions
