...Mark A. Hanson; Bruno Lemaitre ABSTRACT Antimicrobial peptides (AMPs) are innate immune effectors first studied for their role in host defence. Recent studies have implicated these peptides in the clearance of aberrant cells and in neurodegenerative syndromes. In Drosophila , many AMPs are produced...

...Rebeka Popovic; Yizhou Yu; Nuno Santos Leal; Giorgio Fedele; Samantha H. Y. Loh; L. Miguel Martins ABSTRACT Eukaryotic Tribbles proteins are pseudoenzymes that regulate multiple aspects of intracellular signalling. Both Drosophila melanogaster and mammalian members of this family of pseudokinases...

... on mutations in dishevelled 1 (DVL1), an intracellular adaptor protein that is required for both canonical (β-catenin-dependent) or non-canonical (requiring small GTPases and JNK) Wnt signaling. We expressed human wild-type DVL1 or DVL1 variants alongside the endogenous genome of chicken and Drosophila...

... effects and to drug resistance. Thus, identifying compounds that synergise with Ras pathway inhibitors would enable lower doses of the Ras pathway inhibitors to be used and also decrease the acquisition of drug resistance. Here, in a specialised chemical screen using a Drosophila model of Ras-driven...

... P-cadherin Drosophila model. We report that actin nucleators, Mrtf and Srf, are main P-cadherin effectors in fly. We validated these findings in a human mammary epithelial cell line with conditional activation of the SRC oncogene. We show that, prior to promoting malignant phenotypes, SRC induces...

... in multiple signaling pathways, demonstrating an important function in gene expression regulation. To advance disease diagnostics and treatment strategies, we strive to understand the genetic pathways that are perturbed by DGC mutations. Here, we utilized a Drosophila model to investigate the transcriptomic...

... dysfunction is a hallmark of PD, and mutations in PINK1 , a gene necessary for mitochondrial fitness, cause PD. Drosophila melanogaster flies with pink1 mutations exhibit mitochondrial defects and dopaminergic cell loss and are used as a PD model. To gain an integrated view of the cellular changes caused...

... and aggregation is key to understanding disease progression and developing targeted therapeutic approaches. In this study, we identified String (Stg)/Cdc25 phosphatase as a suppressor of abnormal Tau phosphorylation and associated toxicity. Using a Drosophila model of tauopathy, we showed that Tau...

.... Here, using Drosophila as a model system, we observed that the phosphodeficient SREBP proteins (SREBP-Thr390Ala) were more stable and more potent in stimulating the expression of lipogenic genes and promoting lipogenesis in vivo than wild-type SREBP. In addition, starvation blocked the effects of wild...

... to regulate their intrinsic excitability, offers an attractive opportunity to prevent seizures. However, to date, no drug-based interventions have been reported that manipulate this type of neuronal homeostatic mechanism. Here, we used a combination of Drosophila and mouse, and, in the latter, both...

..., but its effect in the context of Barth syndrome has not been examined. We demonstrate, for the first time, that nicotinamide riboside can rescue exercise tolerance and mitochondrial respiration in a Drosophila Tafazzin mutant and that the beneficial effects are dependent on sir2 and spargel...

... whether known neurotoxic modifiers can suppress circadian dysfunction. We performed a screen of neurotoxicity-modifier genes to suppress circadian behavioural arrhythmicity in a Drosophila circadian HD model. The molecular chaperones Hsp40 and HSP70 emerged as significant suppressors in the circadian...

... certain disadvantages in that obtaining results is time-consuming, owing to relatively long lifespans, and these results have low statistical resolution because sample sizes are usually small. Here, we report a targeted genetic screening of 5698 RNAi lines encompassing 4135 Drosophila genes with human...

... how changes in host metabolism contribute to host defence. Using Drosophila as a model system, we identify induction of intestinal target-of-rapamycin (TOR) kinase signalling as a key adaptive metabolic response to enteric infection. We find that enteric infection induces both local and systemic...

... (officially known as Thor in Drosophila and EIF4EBP2 in humans), an ATF4 transcriptional target. Lastly, mutations in human PrP (N159D, D167S, N174S) showed partial protective activity, revealing its high propensity to misfold into toxic conformations. Constructs carrying human PrP-M129, human PrP-V129...

... by producing local and systemic signals that are relayed to the body and that maintain intestinal and organismal homeostasis. Consequently, disruption of intestinal homeostasis and signalling are associated with systemic diseases and multi-organ dysfunction. In recent years, the fruit fly Drosophila...

... to replicate in animal models and are, in part, responsible for the failures in translational cancer research. In this Perspective, we highlight the fruit fly, Drosophila melanogaster , as a powerful model organism to investigate multimorbidity and tumour diversity. We also highlight how harnessing...

... of cachexia, our understanding of how tumors interact with host tissues and how they affect metabolism is limited. Among the challenges of studying tumor–host tissue crosstalk are the complexity of cancer itself and our insufficient knowledge of the factors that tumors release into the blood. Drosophila...

...Jun-yi Zhu; Xiaohu Huang; Yulong Fu; Yin Wang; Pan Zheng; Yang Liu; Zhe Han ABSTRACT Oncogenic Ras mutations are highly prevalent in hematopoietic malignancies. However, it is difficult to directly target oncogenic RAS proteins for therapeutic intervention. We have developed a Drosophila acute...

... proteostasis network extends lifespan and prevents age-related diseases. However, how proteostasis is regulated in different tissues throughout the aging process remains unclear. Here, we show that Drosophila homologs of Cubilin- and Amnionless (dCubilin and dAMN, respectively)-mediated protein reabsorption...