Thursday, July 19, 2018

New fly model of FUS toxicity

Bogaert E, Boeynaems S, Kato M, Guo L, Caulfield TR, Steyaert J, Scheveneels W, Wilmans N, Haeck W, Hersmus N, Schymkowitz J, Rousseau F, Shorter J, Callaerts P, Robberecht W, Van Damme P, Van Den Bosch L. Molecular Dissection of FUS Points at Synergistic Effect of Low-Complexity Domains in Toxicity. Cell Rep. 2018 Jul 17;24(3):529-537.e4. PMID: 30021151.

From the abstract: "RNA-binding protein aggregation is a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). To gain better insight into the molecular interactions underlying this process, we investigated FUS, which is mutated and aggregated in both ALS and FTLD. We generated a Drosophila model of FUS toxicity ..."

Wednesday, July 18, 2018

Review -- Fruit Flies in the study of Human Genetic Disease

Oriel C, Lasko P. Recent Developments in Using Drosophila as a Model for Human Genetic Disease. Int J Mol Sci. 2018 Jul 13;19(7). pii: E2041. PMID: 30011838.

Abstract: "Many insights into human disease have been built on experimental results in Drosophila, and research in fruit flies is often justified on the basis of its predictive value for questions related to human health. Additionally, there is now a growing recognition of the value of Drosophila for the study of rare human genetic diseases, either as a means of validating the causative nature of a candidate genetic variant found in patients, or as a means of obtaining functional information about a novel disease-linked gene when there is little known about it. For these reasons, funders in the US, Europe, and Canada have launched targeted programs to link human geneticists working on discovering new rare disease loci with researchers who work on the counterpart genes in Drosophila and other model organisms. Several of these initiatives are described here, as are a number of output publications that validate this new approach."

Tuesday, July 17, 2018

Drosophila research a highlight in a review article about obesity-related research

Mirth CK, Piper MD. Matching complex dietary landscapes with the signalling pathways that regulate life history traits. Curr Opin Genet Dev. 2017 Dec;47:9-16. doi: 10.1016/j.gde.2017.08.001. PMID: 28822885.

From the abstract: "The rise in obesity in human populations has reinvigorated research focused on how nutrition impacts life history traits, including body size, lifespan, reproductive success, stress resistance and propensity for disease. ... Here, we offer our perspective on how to integrate insights from the cellular to the whole organism to understand the regulation of life history traits."

Wednesday, July 11, 2018

Fly model of cholera used to explore cellular mechanisms of disease

Fast D, Kostiuk B, Foley E, Pukatzki S. Commensal pathogen competition impacts host viability. Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):7099-7104. PMID: 29915049.

From the abstract: "While the structure and regulatory networks that govern type-six secretion system (T6SS) activity of Vibrio cholerae are becoming increasingly clear, we know less about the role of T6SS in disease. Under laboratory conditions, V. cholerae uses T6SS to outcompete many Gram-negative species, including other V. cholerae strains and human commensal bacteria. ... We used the Drosophila melanogaster model of cholera to define the contribution of T6SS to V. cholerae pathogenesis. ... interactions between T6SS and host commensals impact pathogenesis. Inactivation of T6SS, or removal of commensal bacteria, attenuates disease severity. Reintroduction of the commensal, Acetobacter pasteurianus, into a germ-free host is sufficient to restore T6SS-dependent pathogenesis in which T6SS and host immune responses regulate viability. Together, our data demonstrate that T6SS acts on commensal bacteria to promote the pathogenesis of V. cholerae."

Review article: "Insights from intoxicated Drosophila"

Petruccelli E, Kaun KR. Insights from intoxicated Drosophila. Alcohol. 2018 Mar 21. pii: S0741-8329(18)30040-5. doi: 10.1016/j.alcohol.2018.03.004. PMID: 29980341.

The abstract: "Our understanding of alcohol use disorder (AUD), particularly alcohol's effects on the nervous system, has unquestionably benefited from the use of model systems such as Drosophila melanogaster. Here, we briefly introduce the use of flies in alcohol research, and highlight the genetic accessibility and neurobiological contribution that flies have made to our understanding of AUD. Future fly research offers unique opportunities for addressing unresolved questions in the alcohol field, such as the neuromolecular and circuit basis for cravings and alcohol-induced neuroimmune dysfunction. This review strongly advocates for interdisciplinary approaches and translational collaborations with the united goal of confronting the major health problems associated with alcohol abuse and addiction."

Review: Fly models in the study of Friedreich's Ataxia

Monnier V, Llorens JV, Navarro JA. Impact of Drosophila Models in the Study and Treatment of Friedreich's Ataxia. Int J Mol Sci. 2018 Jul 7;19(7). PMID: 29986523.

From the abstract: "Drosophila melanogaster has been for over a century the model of choice of several neurobiologists to decipher the formation and development of the nervous system as well as to mirror the pathophysiological conditions of many human neurodegenerative diseases. The rare disease Friedreich’s ataxia (FRDA) is not an exception. Since the isolation of the responsible gene more than two decades ago, the analysis of the fly orthologue has proven to be an excellent avenue to understand the development and progression of the disease, to unravel pivotal mechanisms underpinning the pathology and to identify genes and molecules that might well be either disease biomarkers or promising targets for therapeutic interventions. In this review, we aim to summarize the collection of findings provided by the Drosophila models but also to go one step beyond and propose the implications of these discoveries for the study and cure of this disorder. ..."

Study investigates impact of human LAMP2A in Drosophila model of Parkinsons disease

Issa AR, Sun J, Petitgas C, Mesquita A, Dulac A, Robin M, Mollereau B, Jenny A, Chérif-Zahar B, Birman S. The lysosomal membrane protein LAMP2A promotes autophagic flux and prevents SNCA-induced Parkinson disease-like symptoms in the Drosophila brain. Autophagy. 2018 Jul 10. PMID: 29989488.

From the abstract: "The autophagy-lysosome pathway plays a fundamental role in the clearance of aggregated proteins and protection against cellular stress and neurodegenerative conditions. Alterations in autophagy processes, including macroautophagy and chaperone-mediated autophagy (CMA), have been described in Parkinson disease (PD). CMA is a selective autophagic process that depends on LAMP2A (Lysosomal associated membrane protein 2A), a mammal and bird-specific membrane glycoprotein that translocates cytosolic proteins containing a KFERQ-like peptide motif across the lysosomal membrane. Drosophila reportedly lack CMA and use endosomal microautophagy (eMI) as an alternative selective autophagic process. Here we report that neuronal expression of human LAMP2A protected Drosophila against starvation and oxidative stress, and delayed locomotor decline in aging flies without extending their lifespan. LAMP2A also prevented the progressive locomotor and oxidative defects induced by neuronal expression of PD-associated human SNCA (synuclein alpha) with alanine-to-proline mutation at position 30 (SNCAA30P). ... These results indicate that LAMP2A can promote autophagosome formation and potentiate autophagic flux in the Drosophila brain, leading to enhanced stress resistance and neuroprotection."