Wednesday, January 3, 2018

Drosophila model points to involvement of potassium channel in aging hearts

Klassen MP, Peters CJ, Zhou S, Williams HH, Jan LY, Jan YN. Age-dependent diastolic heart failure in an in vivo Drosophila model. Elife. 2017 Mar 22;6. pii: e20851. PMID: 28328397; PMCID: PMC5362267.

The abstract: "While the signals and complexes that coordinate the heartbeat are well established, how the heart maintains its electromechanical rhythm over a lifetime remains an open question with significant implications to human health. Reasoning that this homeostatic challenge confronts all pulsatile organs, we developed a high resolution imaging and analysis toolset for measuring cardiac function in intact, unanesthetized Drosophila melanogaster. We demonstrate that, as in humans, normal aging primarily manifests as defects in relaxation (diastole) while preserving contractile performance. Using this approach, we discovered that a pair of two-pore potassium channel (K2P) subunits, largely dispensable early in life, are necessary for terminating contraction (systole) in aged animals, where their loss culminates in fibrillatory cardiac arrest. As the pumping function of its heart is acutely dispensable for survival, Drosophila represents a uniquely accessible model for understanding the signaling networks maintaining cardiac performance during normal aging."

Drosophila gut as model for uncovering mechanisms of antimicrobial activity

Liu X, Hodgson JJ, Buchon N. Drosophila as a model for homeostatic,antibacterial, and antiviral mechanisms in the gut. PLoS Pathog. 2017 May 4;13(5):e1006277. PMID: 28472194; PMCID: PMC5417715.

This review article includes an illustrated comparison of fly and mammalian guts and their interactions with microbes such as bacteria and viruses.

Tuesday, January 2, 2018

Protocol for testing of candidate heart-disease genes in Drosophila

Zhu JY, Fu Y, Richman A, Han Z. Validating Candidate Congenital Heart Disease Genes in Drosophila. Bio Protoc. 2017 Jun 20;7(12). pii: e2350. PMID: 29276722; PMCID: PMC5739056.

From the abstract: "... A high throughput in vivo model system to validate candidate gene association with pathology is ... useful. We present such a system employing Drosophila to validate candidate congenital heart disease (CHD) genes. The protocols exploit comprehensive libraries of UAS-GeneX-RNAi fly strains ... These protocols were recently used to evaluate more than 100 candidate CHD genes implicated by patient whole-exome sequencing (Zhu et al., 2017)."

Protocol for infection of Drosophila with a parasite for research studies related to leishmaniasis

Okuda K, Silverman N. Drosophila Model of Leishmania amazonensis Infection. Bio Protoc. 2017 Dec 5;7(23). pii: e2640. PMID: 29276726; PMCID: PMC5738924.

The abstract: "This protocol describes how to generate and harvest antibody-free L. amazonensis amastigotes, and how to infect adult Drosophila melanogaster with these parasites. This model recapitulates key aspects of the interactions between Leishmania amastigotes and animal phagocytes."

Drosophila model of polycystic kidney disease leads to mechanistic insights

Gamberi C, Hipfner DR, Trudel M, Lubell WD. Bicaudal C mutation causes myc and TOR pathway up-regulation and polycystic kidney disease-like phenotypes in Drosophila. PLoS Genet. 2017 Apr 13;13(4):e1006694. PMID: 28406902; PMCID: PMC5390980.

The abstract: "Progressive cystic kidney degeneration underlies diverse renal diseases, including the most common cause of kidney failure, autosomal dominant Polycystic Kidney Disease (PKD). Genetic analyses of patients and animal models have identified several key drivers of this disease. The precise molecular and cellular changes underlying cystogenesis remain, however, elusive. Drosophila mutants lacking the translational regulator Bicaudal C (BicC, the fly ortholog of vertebrate BICC1 implicated in renal cystogenesis) exhibited progressive cystic degeneration of the renal tubules (so called "Malpighian" tubules) and reduced renal function. The BicC protein was shown to bind to Drosophila (d-) myc mRNA in tubules. Elevation of d-Myc protein levels was a cause of tubular degeneration in BicC mutants. Activation of the Target of Rapamycin (TOR) kinase pathway, another common feature of PKD, was found in BicC mutant flies. Rapamycin administration substantially reduced the cystic phenotype in flies. We present new mechanistic insight on BicC function and propose that Drosophila may serve as a genetically tractable model for dissecting the evolutionarily-conserved molecular mechanisms of renal cystogenesis."

Monday, December 11, 2017

Studies in Drosophila among those contributing to content included in DrugAge database

Barardo D, Thornton D, Thoppil H, Walsh M, Sharifi S, Ferreira S, Anžič A, Fernandes M, Monteiro P, Grum T, Cordeiro R, De-Souza EA, Budovsky A, Araujo N, Gruber J, Petrascheck M, Fraifeld VE, Zhavoronkov A, Moskalev A, de Magalhães JP. The DrugAge database of aging-related drugs. Aging Cell. 2017 Jun;16(3):594-597. PMID: 28299908; PMCID: PMC5418190.

From the abstract: "Aging is a major worldwide medical challenge. Not surprisingly, identifying drugs and compounds that extend lifespan in model organisms is a growing research area. Here, we present DrugAge (http://genomics.senescence.info/drugs/), a curated database of lifespan-extending drugs and compounds. At the time of writing, DrugAge contains 1316 entries featuring 418 different compounds from studies across 27 model organisms, including worms, flies, yeast and mice. Data were manually curated from 324 publications. ... DrugAge is freely available online for the scientific community and will be an important resource for biogerontologists."

Diet-based Drosophila model of kidney stones

Chung VY, Turney BW. A Drosophila genetic model of nephrolithiasis: transcriptional changes in response to diet induced stone formation. BMC Urol. 2017 Nov 28;17(1):109. PMID: 29183349; PMCID: PMC5706311.

From the abstract: "... We have used Drosophila as a genetic model to study the transcriptional response to stone formation secondary to dietary manipulation. ... Wild-type male flies were raised on standard medium supplemented with lithogenic agents: control, sodium oxalate (NaOx) and ethylene glycol (EG). ... Crystal formation was visualized in 20%(±2.2) of flies on control diet, 73%(±3.6) on NaOx diet and 84%(±2.2) on EG diet. ... Fifty-eight genes were differentially expressed (FDR <0.05, p < 0.05) in NaOx diet and 20 genes in EG diet. ... This genetic model could be potentially used to identify the candidate genes that influence stone risk hence providing more insight to the pathogenesis of human stone disease."