Tuesday, December 17, 2013

Neurofibromatosis and fly studies.

Walker JA, Gouzi JY, Long JB, Huang S, Maher RC, Xia H, Khalil K, Ray A, Van Vactor D, Bernards R, Bernards A. Genetic and Functional Studies Implicate Synaptic Overgrowth and Ring Gland cAMP/PKA Signaling Defects in the Drosophila melanogaster Neurofibromatosis-1 Growth Deficiency. PLoS Genet. 2013 Nov;9(11):e1003958. PMID: 24278035; PMCID: PMC3836801.

Drosophila models of diabetes.

He BZ, Ludwig MZ, Dickerson DA, Barse L, Arun B, Vilhjálmsson BJ, Park SY, Tamarina NA, Selleck SB, Wittkopp PJ, Bell GI, Kreitman M. Effect of Genetic Variation in a Drosophila Model of Diabetes-Associated Misfolded Human Proinsulin. Genetics. 2013 Nov 26. PMID: 24281155.

Park SY, Ludwig MZ, Tamarina NA, He BZ, Carl SH, Dickerson DA, Barse L, Arun B, Williams CL, Miles CM, Philipson LH, Steiner DF, Bell GI, Kreitman M. Genetic Complexity in a Drosophila Model of Diabetes-Associated Misfolded Human Proinsulin. Genetics. 2013 Nov 26. PMID: 24281154.

These studies utilize the Drosophila Genome Reference Panel from the MacKay lab.

DGRP information page at the MacKay lab
DGRP search page
Nature paper describing the resource

Hippo pathway and cancer.

Michaloglou C, Lehmann W, Martin T, Delaunay C, Hueber A, Barys L, Niu H, Billy E, Wartmann M, Ito M, Wilson CJ, Digan ME, Bauer A, Voshol H, Christofori G, Sellers WR, Hofmann F, Schmelzle T. The tyrosine phosphatase PTPN14 is a negative regulator of YAP activity. PLoS One. 2013 Apr 16;8(4):e61916. PMID: 23613971; PMCID: PMC3628344.

Fly heart diease model. Impaired Traponin-T.

Cozhimuttam Viswanathan M, Kaushik G, Engler AJ, Lehman WJ, Cammarato A. A Drosophila Melanogaster Model of Diastolic Dysfunction and Cardiomyopathy Based on Impaired Troponin-T Function. Circ Res. 2013 Nov 12. PMID: 24221941.

Flies & Neurodegeration. Database, recent reports and review.

Na D, Rouf M, O Kane CJ, Rubinsztein DC, Gsponer J. NeuroGeM, a knowledgebase of genetic modifiers in neurodegenerative diseases. BMC Med Genomics. 2013 Nov 14;6(1):52. PMID: 24229347; PMCID: PMC3833180.

Vos M, Lovisa B, Geens A, Morais VA, Wagnières G, van den Bergh H, Ginggen A, De Strooper B, Tardy Y, Verstreken P. Near-Infrared 808 nm Light Boosts Complex IV-Dependent Respiration and Rescues a Parkinson-Related pink1 Model. PLoS One. 2013 Nov 11;8(11):e78562. PMID: 24244323; PMCID: PMC3823844.

Riemensperger T, Issa AR, Pech U, Coulom H, Nguyễn MV, Cassar M, Jacquet M, Fiala A, Birman S. A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease. Cell Rep. 2013 Nov 27;5(4):952-60. PMID: 24239353.

Moran MT, Tare M, Kango-Singh M, Singh A. Homeotic Gene teashirt (tsh) Has a Neuroprotective Function in Amyloid-Beta 42 Mediated Neurodegeneration. PLoS One. 2013 Nov 25;8(11):e80829. PMID: 24282556; PMCID: PMC3840013.

Prüßing K, Voigt A, Schulz JB. Drosophila melanogaster as a model organism for Alzheimer's disease. Mol Neurodegener. 2013 Nov 22;8(1):35. PMID: 24267573.

Friday, November 22, 2013

Hyperlocomotion in flies expressing mutant form of hDAT associated with autism.

Hamilton PJ, Campbell NG, Sharma S, Erreger K, Herborg Hansen F, Saunders C, Belovich AN; NIH ARRA Autism Sequencing Consortium, Sahai MA, Cook EH, Gether U, McHaourab HS, Matthies HJ, Sutcliffe JS, Galli A. De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder. Mol Psychiatry. 2013 Dec;18(12):1315-1323. PMID: 23979605.

From the abstract: "De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution at site 356 (hDAT T356M). ... In Drosophila melanogaster, the expression of hDAT T356M in DA neurons-lacking Drosophila DAT leads to hyperlocomotion, a trait associated with DA dysfunction and ASD."

Accompanying image: Hamilton PJ, Campbell NG, Sharma S, Erreger K, Hansen FH, Saunders C, Belovich AN, Sahai MA, Cook EH, Gether U, McHaourab HS, Matthies HJ, Sutcliffe JS, Galli A. Drosophila melanogaster: a novel animal model for the behavioral characterization of autism-associated mutations in the dopamine transporter gene. Mol Psychiatry. 2013 Dec;18(12):1235. PMID: 24253181

Polarity gene Crumbs & A-beta-42-mediated neurodegeneration. Alzhemier's Disease-related fly study.

Steffensmeier AM, Tare M, Puli OR, Modi R, Nainaparampil J, Kango-Singh M, Singh A. Novel Neuroprotective Function of Apical-Basal Polarity Gene Crumbs in Amyloid Beta 42 (Aβ42) Mediated Neurodegeneration. PLoS One. 2013 Nov 18;8(11):e78717. PMID: 24260128.

Wednesday, November 20, 2013

Light treatment and fly Parkinson's Disease model.

Vos M, Lovisa B, Geens A, Morais VA, Wagnières G, van den Bergh H, Ginggen A, De Strooper B, Tardy Y, Verstreken P. Near-Infrared 808 nm Light Boosts Complex IV-Dependent Respiration and Rescues a Parkinson-Related pink1 Model. PLoS One. PMID: 24244323.

From the abstract:  "Irradiating Drosophila pink1 mutants using a single dose of 808 nm light results in a rescue of major systemic and mitochondrial defects."

Mammalian Parkin protein interaction study uses fly data in assigning confidence.

Zanon A, Rakovic A, Blankenburg H, Doncheva NT, Schwienbacher C, Serafin A, Alexa A, Weichenberger CX, Albrecht M, Klein C, Hicks AA, Pramstaller PP, Domingues FS, Pichler I. Profiling of parkin-binding partners using tandem affinity purification. PLoS One. 2013 PMID: 24244333.

Honing in on specific cells involved in locomotion. Parkinson's Disease-related fly study.

Riemensperger T, Issa AR, Pech U, Coulom H, Nguyễn MV, Cassar M, Jacquet M, Fiala A, Birman S. A Single Dopamine Pathway Underlies Progressive Locomotor Deficits in a Drosophila Model of Parkinson Disease. Cell Rep. 2013 Nov 13. PMID: 24239353.

Wednesday, November 13, 2013

Bisphenol A & obesity.

Williams MJ, Wang Y, Klockars A, Lind PM, Fredriksson R, Schiöth HB. Exposure to Bisphenol A (BPA) Affects Lipid Metabolism in Drosophila melanogaster. Basic Clin Pharmacol Toxicol. 2013 Nov 11. doi: 10.1111/bcpt.12170. PMID: 24215246.

From the abstract:  "Exposure to bisphenol A (BPA) in rodents was shown to induce obesity ... We employed the genetically tractable model organism, Drosophila melanogaster, to test the effects of raising them on food containing various concentrations of BPA. ... we conclude that BPA may inhibit lipid recruitment during starvation in Drosophila."

Fungal compound as possible environmental risk factor for Parkinson's Disease.

Inamdar AA, Hossain MM, Bernstein AI, Miller GW, Richardson JR, Bennett JW. Fungal-derived semiochemical 1-octen-3-ol disrupts dopamine packaging and causes neurodegeneration. Proc Natl Acad Sci U S A. 2013 Nov 11. PMID: 24218591.

From the abstract:  "... To date ... suspected environmental risk factors [for Parkinson's Disease] have been man-made chemicals. In this report, we demonstrate ... that the common volatile fungal semiochemical 1-octen-3-ol reduces dopamine levels and causes dopamine neuron degeneration in Drosophila melanogaster. ..."

Thursday, November 7, 2013

Study in mice and flies implicates Parkin in defense against pathogens. Recent report.

Manzanillo PS, Ayres JS, Watson RO, Collins AC, Souza G, Rae CS, Schneider DS, Nakamura K, Shiloh MU, Cox JS. The ubiquitin ligase parkin mediates resistance to intracellular pathogens. Nature. 2013 Sep 26;501(7468):512-6. PMID: 24005326.

Wednesday, November 6, 2013

Fly assays contribute to study focused on chronic mountain sickness (CMS), also known as Monge disease. Recent rerpot.

Zhou D, Udpa N, Ronen R, Stobdan T, Liang J, Appenzeller O, Zhao HW, Yin Y, Du Y, Guo L, Cao R, Wang Y, Jin X, Huang C, Jia W, Cao D, Guo G, Gamboa JL, Villafuerte F, Callacondo D, Xue J, Liu S, Frazer KA, Li Y, Bafna V, Haddad GG. Whole-genome sequencing uncovers the genetic basis of chronic mountain sickness in Andean highlanders. Am J Hum Genet. 2013 Sep 5;93(3):452-62. PMID: 23954164; PMCID: PMC3769925.

Tuesday, November 5, 2013

Fly assays included in Fragile X study. Top3beta RNA topoisomerase. Recent report.

Xu D, Shen W, Guo R, Xue Y, Peng W, Sima J, Yang J, Sharov A, Srikantan S, Yang J, Fox D 3rd, Qian Y, Martindale JL, Piao Y, Machamer J, Joshi SR, Mohanty S, Shaw AC, Lloyd TE, Brown GW, Ko MS, Gorospe M, Zou S, Wang W. Top3β is an RNA topoisomerase that works with fragile X syndrome protein to promote synapse formation. Nat Neurosci. 2013 Sep;16(9):1238-47. PMID: 23912945.

Monday, November 4, 2013

Fly assay helps confirm relevance of ANK3 disruptions to neurodevelopmental disorders. Recent report.

Iqbal Z, Vandeweyer G, van der Voet M, Waryah AM, Zahoor MY, Besseling JA, Roca LT, Vulto-van Silfhout AT, Nijhof B, Kramer JM, Van der Aa N, Ansar M, Peeters H, Helsmoortel C, Gilissen C, Vissers LE, Veltman JA, de Brouwer AP, Frank Kooy R, Riazuddin S, Schenck A, van Bokhoven H, Rooms L. Homozygous and heterozygous disruptions of ANK3: at the crossroads of neurodevelopmental and psychiatric disorders. Hum Mol Genet. 2013 May 15;22(10):1960-70. PMID: 23390136.

From the abstract:  "... The causality of ANK3 mutations in the two families and the role of the gene in cognitive function were supported by memory defects in a Drosophila knockdown model. ...

Friday, November 1, 2013

TDP-43 in fly neurons and glia. Relevance to ALS. Recent report.

Estes PS, Daniel SG, McCallum AP, Boehringer AV, Sukhina AS, Zwick RA, Zarnescu DC. Motor neurons and glia exhibit specific individualized responses to TDP-43 expression in a Drosophila model of amyotrophic lateral sclerosis. Dis Model Mech. 2013 May;6(3):721-33. PMID: 23471911; PubMed Central PMCID: PMC3634655.

From the abstract: "Here we report the phenotypic consequences of expressing wild-type and four different ALS-linked TDP-43 mutations in neurons and glia. ... These findings support the notion that although motor neurons and glia are both involved in ALS pathology, at the cellular level they can exhibit different responses to TDP-43. In addition, our data suggest that individual TDP-43 alleles utilize distinct molecular mechanisms, which will be important for developing therapeutic strategies."

Plant extracts, reactive oxygen and fly models. Recent reports relevant to neurodegenerative disease.

Ng CF, Ko CH, Koon CM, Xian JW, Leung PC, Fung KP, Chan HY, Lau CB. The Aqueous Extract of Rhizome of Gastrodia elata Protected Drosophila and PC12 Cells against Beta-Amyloid-Induced Neurotoxicity. Evid Based Complement Alternat Med. 2013;2013:516741. PMID: 24174977.

2: Jahromi SR, Haddadi M, Shivanandappa T, Ramesh SR. Neuroprotective Effect of Decalepis hamiltonii in Paraquat-Induced Neurotoxicity in Drosophila melanogaster: Biochemical and Behavioral Evidences. Neurochem Res. 2013 Oct 31. PMID: 24173775.

Thursday, October 31, 2013

Discussions with R. Cagan, editor-in-chief of Disease Models & Mechanisms, freely available online.

Cagan R. Bench to bedside with fruit flies: an interview with Ross Cagan. Dis Model Mech. 2013 May;6(3):567-9. doi: 10.1242/dmm.012443.  PMID: 23616076; PMCID: PMC3634641.

Cagan RL, Justice MJ, Tidmarsh GF. Bridging the gap between basic and applied biology: towards preclinical translation. Dis Model Mech. 2013 May;6(3):559-61.doi: 10.1242/dmm.012450. PMID: 23616075; PMCID: PMC3634639.

Production and testing of a nanocomposite drug using fly models of Parkinson's Disease. Recent report.

Siddique YH, Khan W, Singh BR, Naqvi AH. Synthesis of alginate-curcumin nanocomposite and its protective role in transgenic Drosophila model of Parkinson's disease. ISRN Pharmacol. 2013 Sep 19;2013:794582. PMID: 24171120.

Tuesday, October 29, 2013

New fly model: Autism spectrum disorders. Recent report.

Hahn N, Geurten B, Gurvich A, Piepenbrock D, Kästner A, Zanini D, Xing G, Xie W, Göpfert MC, Ehrenreich H, Heinrich R. Monogenic heritable autism gene neuroligin impacts Drosophila social behaviour. Behav Brain Res. 2013 Sep 1;252:450-7. PMID: 23792025.

From the abstract:  "... Drosophila can thus be used to study the contribution of Neuroligins to synaptic function, social interactions and their implication in ASDs. "

Interplay between diet and cancer. Recent report

Hirabayashi S, Baranski TJ, Cagan RL. Transformed Drosophila cells evade diet-mediated insulin resistance through wingless signaling. Cell. 2013 Aug 1;154(3):664-75. PMID: 23911328; PMCID: PMC3800019.

Flies & booze. Recent review.

Devineni AV, Heberlein U. The evolution of Drosophila melanogaster as a model for alcohol research. Annu Rev Neurosci. 2013 Jul 8;36:121-38. PMID: 23642133.

From the abstract:  "... we describe the ecological relationship between flies and ethanol, the effects of ethanol on fly development and behavior, the use of flies as a model for alcohol addiction, and the interaction between ethanol and social behavior. We discuss ... their utility to help decipher the mechanisms underlying the diverse effects of ethanol, including those that mediate ethanol dependence and addiction in humans."

Flies & frontotemporal dementia (FTD3). New study implicates Notch signaling. Recent report.

Cheruiyot A, Lee JA, Gao FB, Ahmad ST. Expression of mutant CHMP2B, an ESCRT-III component involved in frontotemporal dementia, causes eye deformities due to Notch misregulation in Drosophila. FASEB J. 2013 Oct 24. PMID: 24158394.

Fly study sheds light on Pink1/Parkin pathway. Recent report relevant to Parkinson's Disease.

de Castro IP, Costa AC, Celardo I, Tufi R, Dinsdale D, Loh SH, Martins LM. Drosophila ref(2)P is required for the parkin-mediated suppression of mitochondrial dysfunction in pink1 mutants. Cell Death Dis. 2013 Oct 24;4:e873. PMID: 24157867.

From the abstract:  We conclude that Ref(2)P [the fly ortholog of mammalian sequestrome-1 (p62/SQSTM1)] is a crucial downstream effector of a pathway involving Pink1 and Parkin and is responsible for the maintenance of a viable pool of cellular mitochondria by promoting their aggregation and autophagic clearance.

Fly model & drug development for neurodegenerative disease. Copper chelator. Recent report.

Singh SK, Sinha P, Mishra L, Srikrishna S. Neuroprotective Role of a Novel Copper Chelator against Aβ 42 Induced Neurotoxicity. Int J Alzheimers Dis. 2013;2013:567128. PMID: 24159420; PMCID: PMC3789492.

Friday, October 25, 2013

Using fly models of neurodegenerative disease for drug discovery. Recent review.

Konsolaki M. Fruitful research: drug target discovery for neurodegenerative diseases in Drosophila. Expert Opin Drug Discov. 2013 Oct 23. PMID: 24151920.

From the abstract:  "Expert opinion: Full genome genetic screens in Drosophila can lead to the rapid identification of drug target candidates that can be subsequently validated in a vertebrate system."

Wednesday, October 23, 2013

Fruit flies & Cornelia de Lange syndrome. Recent review.

Dorsett D. What fruit flies can tell us about human birth defects. Mo Med. 2013 Jul-Aug;110(4):309-13. PMID: 24003648.

From the abstract: "Here we describe how understanding a gene's function in fruit flies has illuminated the etiology of Cornelia de Lange syndrome."

Tuesday, October 22, 2013

Cuts & closure. Fly models of wound healing. Recent methods report.

Burra S, Wang Y, Brock AR, Galko MJ. Using Drosophila larvae to study epidermal wound closure and inflammation. Methods Mol Biol. 2013;1037:449-61. PMID: 24029952.

TDP-43 fly model of amyotrophic lateral sclerosis. Recent report.

Choksi DK, Roy B, Chatterjee S, Yusuff T, Bakhoum MF, Sengupta U, Ambegaokar S, Kayed R, Jackson GR. TDP-43 Phosphorylation by Casein Kinase I{epsilon} Promotes Oligomerization and Enhances Toxicity In Vivo. Hum Mol Genet. 2013 Oct 8. PMID: 24105464.

Fly poly-Q disease model and heat-shock proteins. Recent report.

Kuo Y, Ren S, Lao U, Edgar BA, Wang T. Suppression of polyglutamine protein toxicity by co-expression of a heat-shock protein 40 and a heat-shock protein 110. Cell Death Dis. 2013 Oct 3;4:e833. PMID: 24091676.

Autolysosomes & neurodegeneration. Recent review.

Ambegaokar SS, Jackson GR. The downward spiral of tau and autolysosomes: a new hypothesis in neurodegeneration. Autophagy. 2012 Jul 1;8(7):1144-5. PMID: 22635052; PMCID: PMC3429552.

Fly screening & Alzheimer's disease. Recent report.

Shulman JM, Imboywa S, Giagtzoglou N, Powers MP, Hu Y, Devenport D, Chipendo P, Chibnik LB, Diamond A, Perrimon N, Brown NH, De Jager PL, Feany MB. Functional screening in Drosophila identifies Alzheimer's disease susceptibility genes and implicates Tau-mediated mechanisms. Hum Mol Genet. 2013 Oct 9. PMID: 24067533.

Peripheral nerve disease & fly research. Review.

Lloyd TE. Axonal transport disruption in peripheral nerve disease: From Jack's discoveries as a resident to recent contributions. J Peripher Nerv Syst. 2012 Dec;17 Suppl 3:46-51. PMID:

Friday, October 18, 2013

Flies & neurodegenerative diseases. Recent review.

Lenz S, Karsten P, Schulz JB, Voigt A. Drosophila as a screening tool to study human neurodegenerative diseases. J Neurochem. 2013 Sep 12. PMID: 24028575.

Hh signaling & disease. Recent review.

Briscoe J, Thérond PP. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol. 2013 Jul;14(7):416-29. PMID: 23719536.

Anesthesia, Alzheimer's disease & flies. Recent report.

Chen CW, Lin WY, Chen KB, Wu YS, Kuo YC, Liu HP, Li CY. Inhalational Anesthetic Sevoflurane Rescues Retina Function in Alzheimer's Disease Transgenic Drosophila. Curr Alzheimer Res. 2013 Oct 10. PMID: 24117114.

Methylene blue, atxia & flies. Recent report.

Tricoire H, Palandri A, Bourdais A, Camadro JM, Monnier V. Methylene blue rescues heart defects in a Drosophila model of Friedreich's ataxia. Hum Mol Genet. 2013 Oct 8. PMID: 24105471.

Copper, flies and Alzheimer's disease. Recent report.

Lang M, Fan Q, Wang L, Zheng Y, Xiao G, Wang X, Wang W, Zhong Y, Zhou B. Inhibition of human high-affinity copper importer Ctr1 orthologous in the nervous system of Drosophila ameliorates Aβ42-induced Alzheimer's disease-like symptoms. Neurobiol Aging. 2013 Nov;34(11):2604-12.PMID: 23827522; PMCID: PMC3770863.

Flies & neuroblastoma. Recent report.

Chand D, Yamazaki Y, Ruuth K, Schönherr C, Martinsson T, Kogner P, Attiyeh EF, Maris J, Morozova O, Marra MA, Ohira M, Nakagawara A, Sandström PE, Palmer RH, Hallberg B. Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma. Dis Model Mech. 2013 Mar;6(2):373-82. PMID: 23104988; PMCID: PMC3597019.

Flies & Gaucher disease. Recent report.

Maor G, Rencus-Lazar S, Filocamo M, Steller H, Segal D, Horowitz M. Unfolded protein response in Gaucher disease: from human to Drosophila. Orphanet J Rare Dis. 2013 Sep 11;8(1):140. PMID: 24020503.

Flies & Huntington's Disease. Recent review.

Krench M, Littleton JT. Modeling Huntington disease in Drosophila: Insights into axonal transport defects and modifiers of toxicity. Fly (Austin). 2013 Sep 10;7(4). PMID: 24022020.

Fly study links intellectual disability gene and parkin-dependent mitophagy. Recent report.

Haddad DM, Vilain S, Vos M, Esposito G, Matta S, Kalscheuer VM, Craessaerts K, Leyssen M, Nascimento RM, Vianna-Morgante AM, De Strooper B, Van Esch H, Morais VA, Verstreken P. Mutations in the intellectual disability gene Ube2a cause neuronal dysfunction and impair parkin-dependent mitophagy. Mol Cell. 2013 PMID: 23685073.

From the abstract:  "we identify RAD6A as a regulator of Parkin-dependent mitophagy and establish a critical role for RAD6A in maintaining neuronal function."

Retinal degeneration-related fly study. Recent report.

Lee J, Song M, Hong S. Negative regulation of the novel norpA(P24) suppressor, diehard4, in the endo-lysosomal trafficking underlies photoreceptor cell degeneration. PLoS Genet. 2013 Jun;9(6):e1003559. doi: 10.1371/journal.pgen.1003559. PMID: 23754968; PMCID: PMC3674991.

Fly kidney stone model & juices. Recent report.

Ho CY, Chen YH, Wu PY, Chang CH, Chen HY, Man KM, Shen JL, Tsai FJ, Lin WY, Lee YJ, Chen WC. Effects of commercial citrate-containing juices on urolithiasis in a Drosophila model. Kaohsiung J Med Sci. 2013 Sep;29(9):488-93. PMID: 24018152.

Tuesday, September 24, 2013

Flies & muscle atrophy--recent review

Piccirillo R, Demontis F, Perrimon N, Goldberg AL. Mechanisms of muscle growth and atrophy in mammals and Drosophila. Dev Dyn. 2013 Aug 29. PMID: 24038488.

The fly & retinal degeneration--recent review

Xiong B, Bellen HJ. Rhodopsin homeostasis and retinal degeneration: lessons from the fly. Trends Neurosci. 2013 Sep 5. PMID: 24012059.

From the abstract: "We review here the molecular signals involved in Rh homeostasis and the mechanisms underlying retinal degeneration in flies, and discuss possible links to human diseases."

Fly models & neurodevelopmental disorders--recent review

Okray Z, Hassan BA. Genetic approaches in Drosophila for the study neurodevelopmental disorders. Neuropharmacology. 2013 May;68:150-6. PMID: 23067575.

From GWAS to functional genetics--fly study related to diabetes and metabolism

Pendse J, Ramachandran PV, Na J, Narisu N, Fink JL, Cagan RL, Collins FS, Baranski TJ. A Drosophila functional evaluation of candidates from human genome-wide association studies of type 2 diabetes and related metabolic traits identifies tissue-specific roles for dHHEX. BMC Genomics. 2013 Feb 27;14:136. PMID: 23445342; PMCID: PMC3608171.

Two recent fly reports related to neurodegenerative diseases

Richards RI, Samaraweera SE, van Eyk CL, O'Keefe LV, Suter CM. RNA pathogenesis via Toll-like receptor-activated inflammation in expanded repeat neurodegenerative diseases. Front Mol Neurosci. 2013 Sep 5;6:25. PMID: 24046729; PMCID: PMC3763583.

Lenz S, Karsten P, Schulz JB, Voigt A. Drosophila as a screening tool to study human neurodegenerative diseases. J Neurochem. 2013 Sep 12. PMID: 24028575.

Fly models in action--study related to Fragile X syndrome

Friedman SH, Dani N, Rushton E, Broadie K. Fragile X mental retardation protein regulates trans-synaptic signaling. Dis Model Mech. 2013 Sep 5. PMID: 24046358.

New fly model--Pantothenate Kinase-Associated Neurodegeneration

Varun P, Hagit T, Uriya B, Sagiv S, Sebastian K. A new in vivo model of pantothenate kinase-associated neurodegeneration reveals a surprising role for transcriptional regulation in pathogenesis. Front Cell Neurosci. 2013 Sep 9;7:146. PMID: 24058333.

Monday, September 16, 2013

Relevant review--NF-Y transcription factor & fly model

Ly LL, Yoshida H, Yamaguchi M. Nuclear transcription factor Y and its roles in cellular processes related to human disease. Am J Cancer Res. 2013 Aug 14;3(4):339-46. PMID: 23977444; PMCID: PMC3744014.

Relevant review--fly model & host defense

Ferrandon D. The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: from resistance to resilience. Curr Opin Immunol. 2013 Feb;25(1):59-70. Review. PMID: 23228366.

Expression of Gaucher disease gene in fly eye

Suzuki T, Shimoda M, Ito K, Hanai S, Aizawa H, Kato T, Kawasaki K, Yamaguchi T, Ryoo HD, Goto-Inoue N, Setou M, Tsuji S, Ishida N. Expression of Human Gaucher Disease Gene GBA Generates Neurodevelopmental Defects and ER Stress in Drosophila Eye. PLoS One. 2013 Aug 2;8(8):e69147. PMID: 23936319; PMCID: PMC3732251.

Tuesday, September 10, 2013

Fly studies relevant to spinal muscular atrophy

Garcia EL, Lu Z, Meers MP, Praveen K, Matera AG. Developmental arrest of Drosophila survival motor neuron (Smn) mutants accounts for differences in expression of minor intron-containing genes. RNA. 2013 Sep 4. PMID: 24006466.

Sen A, Dimlich DN, Guruharsha KG, Kankel MW, Hori K, Yokokura T, Brachat S, Richardson D, Loureiro J, Sivasankaran R, Curtis D, Davidow LS, Rubin LL, Hart AC, Van Vactor D, Artavanis-Tsakonas S. Genetic circuitry of Survival motor neuron, the gene underlying spinal muscular atrophy. Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):E2371-80. PMID: 23757500; PMCID: PMC3696827.

Review includes discussion of fly models of fungal infection

Arvanitis M, Glavis-Bloom J, Mylonakis E. Invertebrate models of fungal infection. Biochim Biophys Acta. 2013 Sep;1832(9):1378-83. PMID: 23517918.

From the abstract: "The purpose of this review is to compare several model hosts that have been used in experimental mycology to-date and to describe their different characteristics and contribution to the study of fungal virulence and the detection of compounds with antifungal properties."

"Small organism, big discoveries"--a review and recent neurodegeneration-related studies that include fly models

Debattisti V, Scorrano L. D. melanogaster, mitochondria and neurodegeneration: small model organism, big discoveries. Mol Cell Neurosci. 2013 Jul;55:77-86. PMID: 22940086.

Vashishtha M, Ng CW, Yildirim F, Gipson TA, Kratter IH, Bodai L, Song W, Lau A, Labadorf A, Vogel-Ciernia A, Troncosco J, Ross CA, Bates GP, Krainc D, Sadri-Vakili G, Finkbeiner S, Marsh JL, Housman DE, Fraenkel E, Thompson LM. Targeting H3K4 trimethylation in Huntington disease. Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):E3027-36. PMID: 23872847; PMCID: PMC3740882.

O'Rourke JG, Gareau JR, Ochaba J, Song W, Raskó T, Reverter D, Lee J, Monteys AM, Pallos J, Mee L, Vashishtha M, Apostol BL, Nicholson TP, Illes K, Zhu YZ, Dasso M, Bates GP, Difiglia M, Davidson B, Wanker EE, Marsh JL, Lima CD, Steffan JS, Thompson LM. SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation. Cell Rep. 2013 Jul 25;4(2):362-75. PMID: 23871671.

Beharry C, Alaniz ME, Alonso AD. Expression of Alzheimer-Like Pathological Human Tau Induces a Behavioral Motor and Olfactory Learning Deficit in Drosophila Melanogaster. J Alzheimers Dis. PMID: 23948901.

Mason RP, Casu M, Butler N, Breda C, Campesan S, Clapp J, Green EW, Dhulkhed D, Kyriacou CP, Giorgini F. Glutathione peroxidase activity is neuroprotective in models of Huntington's disease. Nat Genet. 2013 Aug 25. PMID: 23974869.

Friday, September 6, 2013

Study uses fly model of Alzheimer's disease

Park SH, Lee S, Hong YK, Hwang S, Lee JH, Bang SM, Kim YK, Koo BS, Lee IS, Cho KS. Suppressive effects of SuHeXiang Wan on amyloid-β42-induced extracellular signal-regulated kinase hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer's disease. Biol Pharm Bull. 2013;36(3):390-8. PMID: 23238278.

Relevant review--fly models & tauopathies

Cowan CM, Mudher A. Are tau aggregates toxic or protective in tauopathies? Front Neurol. 2013;4:114. PMID: 23964266; PMCID: PMC3741634.

Relevant technique: Injecting drugs into adult Drosophila

Howlett IC, Tanouye MA. Seizure-Sensitivity in Drosophila Is Ameliorated by Dorsal Vessel Injection of the Antiepileptic Drug Valproate. J Neurogenet. 2013 PMID: 23941042.

Glaucoma, the unfolded protein response, and the fly--relevant review

Anholt RR, Carbone MA. A molecular mechanism for glaucoma: endoplasmic reticulum stress and the unfolded protein response. Trends Mol Med. 2013 Jul 19. PMID: 23876925.

Includes discussion of a fly model--transgenic expression of myocilin.

Fly disease model used in Huntingtons disease study

Arribat Y, Bonneaud N, Talmat-Amar Y, Layalle S, Parmentier ML, Maschat F. A Huntingtin Peptide Inhibits PolyQ-Huntingtin Associated Defects. PLoS One. 2013 PMID:
23861941; PMCID: PMC3701666.

New fly model--pythiosis

Zanette RA, Santurio JM, Loreto ES, Alves SH, Kontoyiannis DP. Toll-deficient Drosophila is susceptible to Pythium insidiosum infection. Microbiol Immunol. 2013 Jul 19. PMID: 23865688.

From the abstract: "There is a paucity of animal models of pythiosis, a life-threatening disease of humans and animals that has poorly understood immunopathogenesis. We developed a pythiosis model ..."

Integrated approach to spinocerebellar ataxia includes Drosophila genetic screens

Park J, Al-Ramahi I, Tan Q, Mollema N, Diaz-Garcia JR, Gallego-Flores T, Lu HC, Lagalwar S, Duvick L, Kang H, Lee Y, Jafar-Nejad P, Sayegh LS, Richman R, Liu X, Gao Y, Shaw CA, Arthur JS, Orr HT, Westbrook TF, Botas J, Zoghbi HY. RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature. 2013 Jun 20;498(7454):325-31. PMID: 23719381.

From the abstract: "We have developed a strategy to identify therapeutic entry points ... this approach, which integrates parallel cell-based and Drosophila genetic screens, ... revealed that downregulation of several components of the RAS-MAPK-MSK1 pathway decreases ATXN1 levels and suppresses neurodegeneration in Drosophila and mice."

Study includes fly assays relevant to fragile X-associated tremor ataxia syndrome

Todd PK, Oh SY, Krans A, He F, Sellier C, Frazer M, Renoux AJ, Chen KC, Scaglione KM, Basrur V, Elenitoba-Johnson K, Vonsattel JP, Louis ED, Sutton MA, Taylor JP, Mills RE, Charlet-Berguerand N, Paulson HL. CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome. Neuron. 2013 May 8;78(3):440-55. PMID: 23602499.

From the abstract: "In Drosophila, CGG repeat toxicity is suppressed by eliminating RAN translation and enhanced by increased polyglycine protein production. These studies expand the growing list of nucleotide repeat disorders in which RAN translation occurs and provide evidence that RAN translation contributes to neurodegeneration."

Thursday, September 5, 2013

Flies & infection.

Ben-Ami R, Watson CC, Lewis RE, Albert ND, Arias CA, Raad II, Kontoyiannis DP. Drosophila melanogaster as a model to explore the effects of methicillin-resistant Staphylococcus aureus strain type on virulence and response to linezolid treatment. Microb Pathog. 2013 Feb;55:16-20. PMID: 23232438.

Diaz L, Kontoyiannis DP, Panesso D, Albert ND, Singh KV, Tran TT, Munita JM, Murray BE, Arias CA. Dissecting the mechanisms of linezolid resistance in a Drosophila melanogaster infection model of Staphylococcus aureus. J Infect Dis. 2013 Jul;208(1):83-91. PMID: 23547139; PMCID: PMC3666140.

See also this post.

Fly model of Alzheimer's disease is used to explore links to copper homeostasis.

Lang M, Fan Q, Wang L, Zheng Y, Xiao G, Wang X, Wang W, Zhong Y, Zhou B. Inhibition of human high-affinity copper importer Ctr1 orthologous in the nervous system of Drosophila ameliorates Aβ42-induced Alzheimer's disease-like symptoms. Neurobiol Aging. 2013 Nov;34(11):2604-12. PMID: 23827522.

From the abstract:  "These results imply that copper may play a causative role in developing AD ... Early manipulation of brain copper uptake can have a great effect on Aβ pathology."

Fly cells and in vivo assays used in Huntingtons study.

Lu B, Al-Ramahi I, Valencia A, Wang Q, Berenshteyn F, Yang H, Gallego-Flores T, Ichcho S, Lacoste A, Hild M, Difiglia M, Botas J, Palacino J. Identification of NUB1 as a suppressor of mutant Huntington toxicity via enhanced protein clearance. Nat Neurosci. 2013 May;16(5):562-70. PMID: 23525043.

New fly model related to neurodegeneration--DRPLA fly model--linking neurodegeneration with autophagy

Charroux B, Fanto M. The fine line between waste disposal and recycling: DRPLA fly models illustrate the importance of completing the autophagy cycle for rescuing neurodegeneration. Autophagy. 2010 Jul;6(5):667-9. PMID: 20543566.

Wednesday, August 14, 2013

Understanding PARK15 (Fbxo7). Parkinson's-related study includes assays in flies.

Burchell VS, Nelson DE, Sanchez-Martinez A, Delgado-Camprubi M, Ivatt RM, Pogson JH, Randle SJ, Wray S, Lewis PA, Houlden H, Abramov AY, Hardy J, Wood NW, Whitworth AJ, Laman H, Plun-Favreau H. The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nat Neurosci. 2013 Aug 11. PMID: 23933751.

Fly model of Gaucher disease. Human protein expressed in fly eye.

Suzuki T, Shimoda M, Ito K, Hanai S, Aizawa H, Kato T, Kawasaki K, Yamaguchi T, Ryoo HD, Goto-Inoue N, Setou M, Tsuji S, Ishida N. Expression of Human Gaucher Disease Gene GBA Generates Neurodevelopmental Defects and ER Stress in Drosophila Eye. PLoS One. 2013 Aug 2;8(8):e69147. PMID: 23936319.

Monday, August 5, 2013

Pre-clinical drug trial for disease with currently "no disease-modifying treatments" includes Drosophila studies

This study focuses on Spinocerebellar ataxia type 3 (SCA3), which the authors indicate is also known as Machado-Joseph Disease (MJD).

Yi J, Zhang L, Tang B, Han W, Zhou Y, Chen Z, Jia D, Jiang H. Sodium valproate alleviates neurodegeneration in SCA3/MJD via suppressing apoptosis and rescuing the hypoacetylation levels of histone H3 and H4. PLoS One. 2013;8(1):e54792. PMID: 23382971; PMCID: PMC3557284.

Using the fly to follow up on GWAS. Heart rate study.

den Hoed et al. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nat Genet. 2013 Jun;45(6):621-31. PMID: 23583979; PMCID: PMC3696959.

From the abstract: "Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. ... Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets."

Wednesday, July 31, 2013

New fly model: Primary Ciliary Dyskinesia

Moore DJ, Onoufriadis A, Shoemark A, Simpson MA, Zur Lage PI, de Castro SC, Bartoloni L, Gallone G, Petridi S, Woollard WJ, Antony D, Schmidts M, Didonna T, Makrythanasis P, Bevillard J, Mongan NP, Djakow J, Pals G, Lucas JS, Marthin JK, Nielsen KG, Santoni F, Guipponi M, Hogg C, Antonarakis SE, Emes RD, Chung EM, Greene ND, Blouin JL, Jarman AP, Mitchison HM. Mutations in ZMYND10, a Gene Essential for Proper Axonemal Assembly of Inner and Outer Dynein Arms in Humans and Flies, Cause Primary Ciliary Dyskinesia. Am J Hum Genet. 2013 Jul 24. PMID: 23891471.

From the abstract: "Using a fly model of PCD [primary ciliary dyskinesia], we conclude that ZMYND10 is a cytoplasmic protein required for IDA [inner dynein arm] and ODA [outer dynein arm] assembly and that its variants cause ciliary dysmotility and PCD with laterality defects."

Tuesday, July 30, 2013

DIOPT-DIST online software tool updated

The DRSC recently updated the back-end database supporting our ortholog-human gene-human disease search tool, for example to add new GWAS data sets. If it's been a while since you checked a favorite fly gene or genes at DIOPT-DIST, might be time to check again.

Wednesday, July 10, 2013

Flies & cancer research. Recent review.

Tipping M, Perrimon N. Drosophila as a model for context-dependent tumorigenesis. J Cell Physiol. 2013 Jul 9. PMID: 23836429.

From the abstract: "We review the organs and tissues that have been used to model tumor formation, and propose new strategies to maximize the potential of Drosophila in cancer research."

Dystonia models. Recent review.

Caldwell KA, Shu Y, Roberts NB, Caldwell GA, O'Donnell JM. Invertebrate models of dystonia. Curr Neuropharmacol. 2013 Jan;11(1):16-29. PMID: 23814534; PMCID: PMC3580786.

From the abstract: "Despite the substantial advances resulting from the identification of these loci, the function of many DYT gene products remains unclear. ... [Worm and fly] models are particularly amenable to large-scale genetic screens for modifiers or additional alleles, which are bolstering our understanding of the molecular functions associated with these gene products. Moreover, the use of invertebrate models for the evaluation of DYT genetic loci and their genetic interaction networks has predictive value and can provide a path forward for therapeutic intervention."

Mycobacterium can infect flies. Recent report.

Oh CT, Moon C, Jeong MS, Kwon SH, Jang J. Drosophila melanogaster model for Mycobacterium abscessus infection. Microbes Infect. 2013 Jul 4. PMID: 23831804.

Wednesday, July 3, 2013

New fly model: αB-crystallin-related cardiomyopathy. Recent report.

Xie HB, Cammarato A, Rajasekaran NS, Zhang H, Suggs JA, Lin HC, Bernstein SI, Benjamin IJ, Golic KG. The NADPH Metabolic Network Regulates Human αB-crystallin Cardiomyopathy and Reductive Stress in Drosophila melanogaster. PLoS Genet. 2013 PMID: 23818860.

Monday, July 1, 2013

RNA binding & neurodegeneration. Recent report.

Ihara R, Matsukawa K, Nagata Y, Kunugi H, Tsuji S, Chihara T, Kuranaga E, Miura M, Wakabayashi T, Hashimoto T, Iwatsubo T. RNA binding mediates neurotoxicity in the transgenic Drosophila model of TDP-43 proteinopathy. Hum Mol Genet. 2013 Jun 25. PMID: 23804749.

From the abstract: "... our results suggest that RNA-binding is key to the neurodegeneration caused by overexpression of TDP-43, and that abnormalities in RNA processing may be crucial to the pathogenesis of TDP-43 proteinopathy."

Also relevant (Update):

Daigle JG, Lanson NA Jr, Smith RB, Casci I, Maltare A, Monaghan J, Nichols CD, Kryndushkin D, Shewmaker F, Pandey UB. RNA-binding ability of FUS regulates neurodegeneration, cytoplasmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations. Hum Mol Genet. 2013 Mar 15;22(6):1193-205. PMID: 23257289; PMCID: PMC3578413.

Friday, June 28, 2013

Flies & aging. Recent review.

Demontis F, Piccirillo R, Goldberg AL, Perrimon N. The influence of skeletal muscle on systemic aging and lifespan. Aging Cell. 2013 Jun 26. PMID: 23802635.

From the abstract: "... we review recent studies in mammals and Drosophila highlighting how nutrient- and stress-sensing in skeletal muscle can influence lifespan and overall aging ..."

Thursday, June 27, 2013

Copper homeostasis, Alzheimer's, Presenilin and fly models. Recent report.

Southon A, Greenough MA, Ganio G, Bush AI, Burke R, Camakaris J. Presenilin promotes dietary copper uptake. PLoS One. 2013 May 7;8(5):e62811. PMID: 23667524; PMCID: PMC3646984.

Nutrition, leucine and a new fly model of Birt-Hogg-Dubé syndrome. Recent report.

In this paper, the authors describe disruption of Drosophila BHD (Folliculin), an ortholog of a tumor suppressor gene associated with the inherited skin disorder Birt-Hogg-Dubé Syndrome. They go on to characterize the mutant phenotype and look at the impact of nutritional interventions on phenotype severity.

Liu W, Chen Z, Ma Y, Wu X, Jin Y, Hou S. Genetic Characterization of the Drosophila Birt-Hogg-Dubé Syndrome Gene. PLoS One. 2013 Jun 17;8(6):e65869. PMID: 23799055.

From the abstract: "Our work provides a new animal model of the BHD syndrome and suggests that modulation of the local nutrient condition might be a potential treatment of the BHD lesions."

Fly models of sleep disorders. Recent review.

Freeman AA, Syed S, Sanyal S. Modeling the genetic basis for human sleep disorders in Drosophila. Commun Integr Biol. 2013 Jan 1;6(1):e22733. PMID: 23802043.

From the abstract: "Sleep research in Drosophila is ... making impressive strides towards helping us understand the biological basis for and the purpose of sleep ..."

Wednesday, June 26, 2013

New fly model of epilepsy. Sodium channels. Recent report.

Howlett IC, Rusan ZM, Parker L, Tanouye MA. Drosophila as a Model for Intractable Epilepsy: gilgamesh Suppresses Seizures in parabss1 Heterozygote Flies. G3 (Bethesda). 2013 Jun 24. PMID: 23797108.

Fly models, oxidative stress, cell death, and Parkinson's disease. Recent report.

Hwang S, Song S, Hong YK, Choi G, Suh YS, Han SY, Lee M, Park SH, Lee JH, Lee S, Bang SM, Jeong Y, Chung WJ, Lee IS, Jeong G, Chung J, Cho KS. Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO. PLoS Genet. 2013 Apr;9(4):e1003412. PMID: 23593018; PMCID: PMC3616925.

Fly study related to Rett syndrome and Angelman syndrome. Recent report.

Kim S, Chahrour M, Ben-Shachar S, Lim J. Ube3a/E6AP is involved in a subset of MeCP2 functions. Biochem Biophys Res Commun. 2013 Jun 19. PMID: 23791832.

Tuesday, June 25, 2013

New approach for study of learning and memory in flies. Relevance to disease-related study. Recent report.

The authors indicate relevance to "neurological pathologies such as Parkinson's disease, Alzheimer's disease, addiction, epilepsy and autism spectrum disorders."

Mejia M, Heghinian MD, Marí F, Godenschwege TA. New Tools for Targeted Disruption of Cholinergic Synaptic Transmission in Drosophila melanogaster. PLoS One. 2013 May 30;8(5):e64685. PMID: 23737994; PMCID: PMC3667824.

Genetic modifiers related to spinal muscular atrophy. Recent report.

Sen A, Dimlich DN, Guruharsha KG, Kankel MW, Hori K, Yokokura T, Brachat S, Richardson D, Loureiro J, Sivasankaran R, Curtis D, Davidow LS, Rubin LL, Hart AC, Van Vactor D, Artavanis-Tsakonas S. Genetic circuitry of Survival motor neuron, the gene underlying spinal muscular atrophy. Proc Natl Acad Sci U S A. 2013 Jun 11. PMID: 23757500.

From the abstract: "... we applied in vivo, in vitro, and in silico approaches to identify genetic and biochemical interactors of the Drosophila SMN homolog."

The physiology of alcohol dependence. Recent review.

From the abstract: "... Drosophila show conserved alcohol tolerance and withdrawal phenotypes indicating that Drosophila genetics can now be used ..." Robinson BG, Khurana S, Atkinson NS. Drosophila larvae as a model to study physiological alcohol dependence. Commun Integr Biol. 2013 Mar 1;6(2):e23501. PMID: 23750304; PMCID: PMC3609852.

Wednesday, June 12, 2013

Retinal degeneration/dystrophy & the fly. Recent report.

Lee J, Song M, Hong S. Negative Regulation of the Novel norpA(P24) Suppressor, diehard4, in the Endo-lysosomal Trafficking Underlies Photoreceptor Cell Degeneration. PLoS Genet. 2013 un;9(6):e1003559. Epub 2013 Jun 6. PMID: 23754968.

From the abstract:  "Our results demonstrate the existence of negative regulation in vesicular traffic between endosomes and lysosomes. We anticipate that the identification of additional components and an in-depth description of this specific molecular machinery will aid in therapeutic interventions of various retinal dystrophies and GPCR-related human diseases."

Using flies to study drug-resistant Staphylococcus aureus.

This report is freely available at PubMed Central.

Wu K, Conly J, Surette M, Sibley C, Elsayed S, Zhang K. Assessment of virulence diversity of methicillin-resistant Staphylococcus aureus strains with a Drosophila melanogaster infection model. BMC Microbiol. PMID: 23176146; PMCID: PMC3539928.

Methods Report: Purification of Fragile-X protein ortholog complexes from Drosophila cells

Miyoshi K, Ogino A, Siomi MC, Siomi H. Purification of dFMR1-Containing Complexes Using Tandem Affinity Purification. Methods Mol Biol. 2013;1010:111-21. PMID: 23754222.

Monday, June 10, 2013

New fly model: VCP mutation-dependent degeneration. Recent report.

Kim NC, Tresse E, Kolaitis RM, Molliex A, Thomas RE, Alami NH, Wang B, Joshi A, Smith RB, Ritson GP, Winborn BJ, Moore J, Lee JY, Yao TP, Pallanck L, Kundu M, Taylor JP. VCP is essential for mitochondrial quality control by PINK1/Parkin and this function is impaired by VCP mutations. Neuron. 2013 Apr 10;78(1):65-80. PMID: 23498974.

From the abstract: "Mutations in VCP cause multisystem degeneration impacting the nervous system, muscle, and/or bone. Patients may present with ALS, Parkinsonism, frontotemporal dementia, myopathy, Paget's disease, or a combination of these. The disease mechanism is unknown. We developed a Drosophila model of VCP mutation-dependent degeneration."

A related paper using human cells appears in the same issue of the journal. Bartolome et al. Pathogenic VCP mutations induce mitochondrial uncoupling and reduced ATP levels. Neuron. 2013 Apr 10;78(1):57-64. PMID: 23498975.

Friday, June 7, 2013

Oxidative stress & a GALT-null Drosophila model of classic galactosemia. Recent report.

Jumbo-Lucioni PP, Hopson ML, Hang D, Liang Y, Jones DP, Fridovich-Keil JL. Oxidative stress contributes to outcome severity in a Drosophila melanogaster model of classic galactosemia. Dis Model Mech. 2013 Jan;6(1):84-94. PMID: 22773758; PMCID: PMC3529341.

From the Translantion Impact statement:  "These findings indicate that oxidative stress and/or the physiological response to oxidative stress might play a role in classic galactosemia in humans, opening up new opportunities for diagnosis, prognosis and treatment."

Thursday, June 6, 2013

Injury, the gut and cancer. Recent report.

Guo Z, Driver I, Ohlstein B. Injury-induced BMP signaling negatively regulates Drosophila midgut homeostasis. J Cell Biol. 2013 Jun 3. PMID: 23733344.

From the abstract: "Loss of BMP signaling pathway members ...  resulted in phenotypes similar to those described for juvenile polyposis syndrome ... Our data ... may provide insight into how BMP signaling mutations drive formation of human intestinal cancers."

Fly model of calcium overload-induced necrosis. Relevance to several diseases. Recent methods report.

Liu K, Li Y, Liu L. Modeling calcium-overload mediated necrosis in Drosophila. Methods Mol Biol. 2013;1004:203-13. PMID: 23733579.

Flies, sleep & Alzheimers. Recent report.

From the abstract:  "Our findings reveal a novel mechanism for Tip60 mediated sleep-wake regulation ... and provide insight into epigenetic-based regulation of sleep disturbances observed in neurodegenerative diseases like Alzheimer's disease."

Pirooznia SK, Chiu K, Chan MT, Zimmerman JE, Elefant F. Epigenetic regulation of axonal growth of Drosophila pacemaker cells by histone acetyltransferase tip60 controls sleep. Genetics. 2012 Dec;192(4):1327-45. PMID: 22982579; PMCID: PMC3512142.

See also this post on a related paper from the same lab group.

Fly models & Alzheimers disease. Regulation of PAR-1. Recent report.

From the abstract:  "Our results provide new insights ... and offer new therapeutic strategies for diseases involving PAR-1/MARK deregulation."

Lee S, Wang JW, Yu W, Lu B. Phospho-dependent ubiquitination and degradation of PAR-1 regulates synaptic morphology and tau-mediated Aβ toxicity in Drosophila. Nat Commun. 2012;3:1312. PMID: 23271647.

Recent review: Fly models of fragile X syndrome

From the abstract: "Several clinical trials are in progress now that were motivated by this research."

McBride SM, Holloway SL, Jongens TA. Using Drosophila as a tool to identify Pharmacological Therapies for Fragile X Syndrome. Drug Discov Today Technol. 2012 Sep 24;10(1):e129-e136. PMID: 23730322.

Related blog posts include this one.

Tuesday, June 4, 2013

Fly models of ALS and frontotemporal lobar degeneration. Links to glutamate transport. Recent report.

Diaper DC, Adachi Y, Lazarou L, Greenstein M, Simoes FA, Di Domenico A, Solomon DA, Lowe S, Alsubaie R, Cheng D, Buckley S, Humphrey DM, Shaw CE, Hirth F. Drosophila TDP-43 dysfunction in glia and muscle cells cause cytological and behavioral phenotypes that characterize ALS and FTLD. Hum Mol Genet. 2013 May 31. PMID: 23727833.

Monday, June 3, 2013

Using the fly to find genetic modifiers of polyglutamine-induced toxicity

VoSSfeldt H, Butzlaff M, PrüSSing K, Ní Chárthaigh RA, Karsten P, Lankes A, Hamm S, Simons M, Adryan B, Schulz JB, Voigt A. Large-scale screen for modifiers of ataxin-3-derived polyglutamine-induced toxicity in Drosophila. PLoS One. 2012;7(11):e47452. PMID: 23139745; PMCID: PMC3489908.

Recent review: Flies as a model to study aging.

Brandt A, Vilcinskas A. The Fruit Fly Drosophila melanogaster as a Model for Aging Research. Adv Biochem Eng Biotechnol. 2013 Apr 19. PMID: 23604209.

New fly model of mitochondrial diseases related to tRNA synthetases

Guitart T, Picchioni D, Piñeyro D, Ribas de Pouplana L. Human mitochondrial disease-like symptoms caused by a reduced tRNA aminoacylation activity in flies. Nucleic Acids Res. 2013 May 15. PMID: 23677612.

Mammalian Itpr1 can provide function in IP(3)R mutant flies. Recent report related to spinocerebellar ataxia.

Chakraborty S, Hasan G. Functional complementation of Drosophila itpr mutants by rat Itpr1. J Neurogenet. 2012 Sep;26(3-4):328-37. PMID: 22817477.

Sunday, June 2, 2013

Flies, sugar and heart disease. Recent report.

Not all fly models of disease start with a genetic mutation or disruption. Some start with a treatment or nutritional change--in this case, a high-sugar diet.

Na J, Musselman LP, Pendse J, Baranski TJ, Bodmer R, Ocorr K, Cagan R. A Drosophila model of high sugar diet-induced cardiomyopathy. PLoS Genet. 2013;9(1):e1003175. PMID: 23326243; PMCID: PMC3542070.

From the abstract:  "Our data establish Drosophila as a useful system for exploring specific aspects of diet-induced heart dysfunction and emphasize enzymes within the hexosamine biosynthetic pathway as candidate therapeutic targets."

Friday, May 31, 2013

Recent report: Parallel work in mouse and fly related to facioscapulohumeral muscular dystrophy

Neguembor MV, Xynos A, Onorati MC, Caccia R, Bortolanza S, Godio C, Pistoni M, Corona DF, Schotta G, Gabellini D. FSHD muscular dystrophy region gene 1 binds Suv4-20h1 histone methyltransferase and impairs myogenesis. J Mol Cell Biol. 2013 May 29. PMID: 23720823.

Four recent papers related to flies and neurodegeneration.

The recent paper have in common that they relate to neurodegenerative diseases.

Samaraweera SE, O'Keefe LV, van Eyk CL, Lawlor KT, Humphreys DT, Suter CM, Richards RI. Modeling and Analysis of Repeat RNA Toxicity in Drosophila. Methods Mol Biol. 2013;1017:173-192. PMID: 23719916.

Song W, Smith MR, Syed A, Lukacsovich T, Barbaro BA, Purcell J, Bornemann DJ, Burke J, Marsh JL. Morphometric Analysis of Huntington's Disease Neurodegeneration in Drosophila. Methods Mol Biol. 2013;1017:41-57. PMID: 23719906.

Ju H, Kokubu H, Todd TW, Kahle JJ, Kim S, Richman R, Chirala K, Orr HT, Zoghbi HY, Lim J. Polyglutamine Disease Toxicity Is Regulated by Nemo-like Kinase in Spinocerebellar Ataxia Type 1. J Neurosci. 2013 May 29;33(22):9328-9336. PMID: 23719801.

Park J, Al-Ramahi I, Tan Q, Mollema N, Diaz-Garcia JR, Gallego-Flores T, Lu HC, Lagalwar S, Duvick L, Kang H, Lee Y, Jafar-Nejad P, Sayegh LS, Richman R, Liu X, Gao Y, Shaw CA, Arthur JS, Orr HT, Westbrook TF, Botas J, Zoghbi HY. RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature. 2013 May 29. PMID: 23719381.

Tuesday, May 28, 2013

Screen in fly model of the myopathy Myotonic Dystrophy Type 1

This study related to Myotonic Dystrophy Type 1 crosses the bridge from fly screen (eye phenotype readout) to mammalian cell follow-up studies.

de Haro M, Al-Ramahi I, Jones KR, Holth JK, Timchenko LT, Botas J. Smaug/SAMD4A Restores Translational Activity of CUGBP1 and Suppresses CUG-Induced Myopathy. PLoS Genet. 2013 Apr;9(4):e1003445. PMID: 23637619; PMCID: PMC3630084.

Monday, May 27, 2013

Catching up--recent papers on brain-related studies

Shaltiel-Karyo R, Frenkel-Pinter M, Rockenstein E, Patrick C, Levy-Sakin M,Schiller A, Egoz-Matia N, Masliah E, Segal D, Gazit E. A BBB Disrupter is also a Potentalpha-Synuclein (alpha-syn) Aggregation Inhibitor: A Novel Dual Mechanism of Mannitol for the Treatment of Parkinson's Disease (PD). J Biol Chem. 2013 May 1. PMID: 23637226.

Esposito G, Vos M, Vilain S, Swerts J, De Sousa Valadas J, Van Meensel S, Schaap O, Verstreken P. Aconitase Causes Iron Toxicity in Drosophila pink1 Mutants. PLoS Genet. 2013 Apr;9(4):e1003478. PMID: 23637640; PMCID: PMC3636082.

Haddad DM, Vilain S, Vos M, Esposito G, Matta S, Kalscheuer VM, Craessaerts K, Leyssen M, Nascimento RM, Vianna-Morgante AM, De Strooper B, Van Esch H, Morais VA, Verstreken P. Mutations in the Intellectual Disability Gene Ube2a Cause Neuronal Dysfunction and Impair Parkin-Dependent Mitophagy. Mol Cell. 2013 May 14. PMID: 23685073.

Soldano A, Okray Z, Janovska P, Tmejová K, Reynaud E, Claeys A, Yan J, Atak ZK, De Strooper B, Dura JM, Bryja V, Hassan BA. The Drosophila Homologue of the Amyloid Precursor Protein Is a Conserved Modulator of Wnt PCP Signaling. PLoS Biol. 2013 May;11(5):e1001562. PMID: 23690751; PMCID: PMC3653798.

Saturday, May 25, 2013

Using Drosophila to study blast injury. Recent report.

Hockey KS, Hubbard WB, Sajja VS, Sholar CA, Thorpe C, Vandevord PJ, Rzigalinski BA. A new model for mild blast injury utilizing Drosophila melanogaster - biomed 2013. Biomed Sci Instrum. 2013;49:134-40. PubMed PMID: 23686192.

Wednesday, May 15, 2013

Sneak Preview: TRiP VAL20 in vivo RNAi fly stocks corresponding to highest-confidence fly disease gene orthologs

The DRSC/TRiP has launched a new web page that lists highest confidence fly orthologs of disease genes (DIOPT scores of 8, 9 or 10 at the time of analysis). This list is limited to human genes associated with disease at the NCBI Online Mendelian Inheritance in Man database (DIOPT-DIST search results will also report associations based on GWAS data).

The page lets you see if there are TRiP VALIUM20 fly stocks for these genes at the Bloomington Drosophila Stock Center. With links to details about the fly genes, human genes, etc. All of the genes on this list have been nominated and are in production for VAL20 TRiP fly stocks.

This resource should help you look at the reduction-of-function RNAi knockdown phenotypes of disease gene orthologs to develop new disease models or otherwise study gene function.

Expert tip:  To view the specific disease or diseases associated with a gene, click the DIOPT score. If you want to then expand the gene candidates list, you can use DIOPT-DIST to search for more genes that match the same disease term or use DIOPT to search for more orthologs of the human gene.

Tuesday, April 23, 2013

Classic Galactosemia (aka Type I Galactosemia) and long-term outcomes. Characterization of a fly model. Recent report.

Ryan EL, DuBoff B, Feany MB, Fridovich-Keil JL. Mediators of a long-term movement abnormality in a Drosophila melanogaster model of classic galactosemia. Dis Model Mech. 2012 Nov;5(6):796-803. doi: 10.1242/dmm.009050. PMID: 22736462; Now freely available at PMCID: PMC3484862.

From the abstract:  "... our results confirm that, like human patients, GALT-null Drosophila experience significant long-term complications that occur independently of galactose exposure, and serve as a proof of principle demonstrating utility of the GALT-null Drosophila model as a tool for exploring genetic and environmental modifiers of long-term outcome in GALT deficiency."

See this post for comments from Annette Parks regarding galactosemia model fly stocks at BDSC.

Monday, April 22, 2013

Human SOD in flies. Consequences of expression in motorneurons. Relevance to ALS. Recent report.

Petrosyan A, Gonçalves OF, Hsieh IH, Phillips JP, Saberi K. Enhanced Optomotor Efficiency by Expression of the Human Gene Superoxide Dismutase Primarily in Drosophila Motorneurons. J Neurogenet. 2013 Apr 18. PubMed PMID: 23597337.

Wednesday, April 17, 2013

The Fly & Physiology. Recent review.

Neckameyer WS, Argue KJ. Comparative approaches to the study of physiology: Drosophila as a physiological tool. Am J Physiol Regul Integr Comp Physiol. 2013 Feb;304(3):R177-88.  PMID: 23220476.

In the summary, the authors state that "The contributions of the Drosophila model to our understanding of numerous diverse physiological pathways cannot be overemphasized ... so much of what we now realize to be of critical significance in the etiology of human disease can trace its lineage to genetic mutations identified in Drosophila."

Effects of a microtubule-stabilizing drug on fly model of tauopathy. Recent report.

Quraishe S, Cowan CM, Mudher A. NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy. Mol Psychiatry. 2013 Apr 16. PMID: 23587881.

Tuesday, April 16, 2013

Mitochondrial disorders. New fly disease model. Recent report.

Studies in Drosophila contribute to characterization of a human gene newly implicated in disease. Table 2 of the paper presents a comparison of the human disease and fly knockdown phenotypes.

van Bon BW, Oortveld MA, Nijtmans LG, Fenckova M, Nijhof B, Besseling J, Vos M, Kramer JM, de Leeuw N, Castells-Nobau A, Asztalos L, Viragh E, Ruiter M, Hofmann F, Eshuis L, Collavin L, Huynen MA, Asztalos Z, Verstreken P, Rodenburg RJ, Smeitink JA, de Vries BB, Schenck A. CEP89 is required for mitochondrial metabolism and neuronal function in man and fly. Hum Mol Genet. 2013 Apr 10. PMID: 23575228.

Hippo pathway in mice vs. flies. Relevant to cancer and cancer models. Recent report.

Bossuyt W, Chen CL, Chen Q, Sudol M, McNeill H, Pan D, Kopp A, Halder G. An evolutionary shift in the regulation of the Hippo pathway between mice and flies. Oncogene. 2013 Apr 8. PubMed PMID: 23563179.

Cardiac hypertrophy. Ras mutant forms. Recent report.

Yu L, Daniels J, Glaser AE, Wolf MJ. Raf-mediated cardiac hypertrophy in adult Drosophila. Dis Model Mech. 2013 Apr 4. PubMed PMID: 23580199.

Flies & Worms & Spinal Myscular Atrophy. Recent report.

Dimitriadi M, Kye MJ, Kalloo G, Yersak JM, Sahin M, Hart AC. The Neuroprotective Drug Riluzole Acts via Small Conductance Ca2+-Activated K+ Channels to Ameliorate Defects in Spinal Muscular Atrophy Models. J Neurosci. 2013 Apr 10;33(15):6557-62. PubMed PMID: 23575853.

From the abstract: "... parallel genetic screens were undertaken in Drosophila and Caenorhabditis elegans SMA models to identify modifiers of the SMN loss of function phenotypes ... We examine here the impact of riluzole in two different SMA models. ... We propose that riluzole improves motor neuron function by acting on SK channels and suggest that SK channels may be important therapeutic targets for SMA patients."

Monday, April 15, 2013

Relevance of fly model of Friedreich's ataxia to drug discovery. Recent report.

Soriano S, Llorens JV, Sobero LB, Gutiérrez L, Calap-Quintana P, Morales MP, Moltó MD, Martínez-Sebastián MJ. Deferiprone and idebenone rescue frataxin depletion phenotypes in a Drosophila model of Friedreich's ataxia. Gene. 2013 Mar 28. PubMed PMID: 23542074.

From the abstract: "These results validate the use of our Drosophila model of FRDA to screen for therapeutic molecules to treat this disease."

Drosophila Alzheimer's disease model & Tip60 HAT activity. Recent report.

Pirooznia SK, Sarthi J, Johnson AA, Toth MS, Chiu K, Koduri S, Elefant F. Tip60 HAT activity  mediates APP induced lethality and apoptotic cell death in the CNS of a Drosophila  Alzheimer's disease model. PLoS One. 2012;7(7):e41776. PubMed PMID: 22848598; PubMed Central PMCID: PMC3406101.

RNA expansion-induced neurodegeneration. Fly model. Recent report.

Samaraweera SE, O'Keefe LV, Price GR, Venter DJ, Richards RI. Distinct roles for Toll and  autophagy pathways in double-stranded RNA toxicity in a Drosophila model of expanded repeat neurodegenerative diseases. Hum Mol Genet. 2013 Mar 29. PubMed PMID: 23525903.

PINK1, Parkin & TRAP. Flies & Parkinson's Disease. Recent report.

Zhang L, Karsten P, Hamm S, Pogson JH, Müller-Rischart AK, Exner N, Haass C, Whitworth AJ, Winklhofer KF, Schulz JB, Voigt A. TRAP1 rescues PINK1 loss-of-function phenotypes. Hum Mol Genet. 2013 Apr 7. PubMed PMID: 23525905.

NF kappa B activation & neurodegeneration. Recent report.

Petersen AJ, Katzenberger RJ, Wassarman DA. The Innate Immune Response Transcription Factor Relish is Necessary for Neurodegeneration in a Drosophila Model of Ataxia-telangiectasia. Genetics. 2013 Mar 15. PubMed PMID: 23502677.

See also a previous post on the innate immune response pathway & neurodegenerative disease.

Friday, April 12, 2013

Huntington's Disease. Validation of a fly model. Recent report.

Zala D, Hinckelmann MV, Saudou F. Huntingtin's Function in Axonal Transport Is Conserved in Drosophila melanogaster. PLoS One. 2013;8(3):e60162. PubMed PMID: 23555909; PubMed Central PMCID: PMC3610688.

From the abstract: "These results suggest that the function of HTT in axonal transport is conserved between flies and mammals. Our study therefore validates Drosophila melanogaster as a model to study HTT function, and its dysfunction associated with HD."

Huntington's Disease & the fly. Wingless signaling & therapeutics.

Dupont P, Besson MT, Devaux J, Liévens JC. Reducing canonical Wingless/Wnt signaling pathway confers protection against mutant Huntingtin toxicity in Drosophila. Neurobiol Dis. 2012 Aug;47(2):237-47. doi: 10.1016/j.nbd.2012.04.007. PubMed PMID: 22531500.

From the abstract: "Our findings highlight that restoring canonical Wg/Wnt signaling may be of therapeutic value."

Liebenberg syndrome & the fly.

Now freely available at PMC: 

Spielmann M, Brancati F, Krawitz PM, Robinson PN, Ibrahim DM, Franke M, Hecht J, Lohan S, Dathe K, Nardone AM, Ferrari P, Landi A, Wittler L, Timmermann B, Chan D, Mennen U, Klopocki E, Mundlos S. Homeotic arm-to-leg transformation associated with genomic rearrangements at the PITX1 locus. Am J Hum Genet. 2012 PubMed PMID: 23022097; PubMed Central PMCID: PMC3484647.

For a link to a general-audience piece on this topic, see this past post.

Understanding neurodegeneration in ALS. Recent report.

Forrest S, Chai A, Sanhueza M, Marescotti M, Parry K, Georgiev A, Sahota V, Mendez-Castro R, Pennetta G. Increased levels of phosphoinositides cause neurodegeneration in a Drosophila model of amyotrophic lateral sclerosis. Hum Mol Genet. 2013 Mar 29. PubMed PMID: 23492670.

Two reports involving human tau-based fly disease models. Recent report.

Xiong Y, Zhao K, Wu J, Xu Z, Jin S, Zhang YQ. HDAC6 mutations rescue human tau-induced  microtubule defects in Drosophila. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4604-9. doi: 10.1073/pnas.1207586110. PubMed PMID: 23487739; PubMed Central PMCID: PMC3606981.

Wu TH, Lu YN, Chuang CL, Wu CL, Chiang AS, Krantz DE, Chang HY. Loss of vesicular dopamine release precedes tauopathy in degenerative dopaminergic neurons in a Drosophila model expressing human tau. Acta Neuropathol. 2013 Mar 15. PubMed PMID: 23494099.

Cinnamon, flies & neuronal degeneration. Recent report.

Shaltiel-Karyo R, Davidi D, Frenkel-Pinter M, Ovadia M, Segal D, Gazit E. Differential inhibition of α-synuclein oligomeric and fibrillar assembly in parkinson's disease model by cinnamon extract. Biochim Biophys Acta. 2012 Oct;1820(10):1628-35. doi: 10.1016/j.bbagen.2012.04.021. PubMed PMID: 22575665.

Identification of "a previously unknown causative factor for metabolic syndrome in humans" using flies. Recent report.

Subramanian M, Metya SK, Sadaf S, Kumar S, Schwudke D, Hasan G. Altered lipid homeostasis in Drosophila InsP3 receptor mutants leads to obesity and hyperphagia. Dis Model Mech. 2013 Mar 15. PubMed PMID: 23471909.

New Fly Model of Myotonic Dystrophy. Recent Report.

Picchio L, Plantie E, Renaud Y, Poovthumkadavil P, Jagla K. Novel Drosophila model of myotonic dystrophy type 1: phenotypic characterization and genome-wide view of altered gene expression. Hum Mol Genet. 2013 Apr 3. PubMed PMID: 23525904.

From the abstract: "we found the calcium pump dSERCA as a Mbl splice target and show that the membrane dSERCA isoform is sufficient to rescue a DM1-induced hypercontraction phenotype in a Drosophila model."

Thursday, April 4, 2013

ALS & the fly. Human disease-associated SOD1 mutations in the fly. Recent report.

Kumimoto EL, Fore TR, Zhang B. Transcriptome Profiling Following Neuronal and Glial Expression of ALS-Linked SOD1 in Drosophila. G3 (Bethesda). 2013 Mar 11. PMID: 23550139.

Friday, March 22, 2013

Drosophila & kidney stones. Recent review.

Miller J, Chi T, Kapahi P, Kahn AJ, Kim MS, Hirata T, Romero MF, Dow JA, Stoller ML. Drosophila Melanogaster as an Emerging Translational Model of Human Nephrolithiasis. J Urol. 2013 Mar 7. doi:pii: S0022-5347(13)03645-8. PubMed PMID: 23500641.

From the abstract:  "The ability to readily manipulate and quantify stone formation in D. melanogaster models of human nephrolithiasis presents the urologic community with a unique opportunity to increase our understanding of this enigmatic disease."

To view more blog posts on kidney stones (nephrolithiasis) click here.

Thursday, March 7, 2013

TBI, SCI & the fly. Recent review.

Nerve injury includes traumatic brain injury (TBI) and spinal cord injury (SCI).

Fang Y, Bonini NM. Axon degeneration and regeneration: insights from Drosophila models of nerve injury. Annu Rev Cell Dev Biol. 2012;28:575-97. doi: 10.1146/annurev-cellbio-101011-155836. Review. PubMed PMID: 22831639.

From the abstract: "Genetically approachable model organisms such as Drosophila melanogaster, the fruit fly, have proven exceptionally successful in modeling human neurodegenerative diseases. More recently, this success has been extended into the field of acute axon injury and regeneration."

Flies & Alcoholism. Recent review.

Robinson BG, Atkinson NS. Is alcoholism learned? Insights from the fruit fly. Curr Opin Neurobiol. 2013 Feb 22. PubMed PMID: 23462335.

Troyer syndrome. New fly model. Recent report.

Troyer syndrome is one of several hereditary spastic paraplegias.

Nahm M, Lee MJ, Parkinson W, Lee M, Kim H, Kim YJ, Kim S, Cho YS, Min BM, Bae YC, Broadie K, Lee S. Spartin Regulates Synaptic Growth and Neuronal Survival by
Inhibiting BMP-Mediated Microtubule Stabilization. Neuron. 2013 Feb 20;77(4):680-95. doi: 10.1016/j.neuron.2012.12.015. PubMed PMID: 23439121.

Wednesday, March 6, 2013

Uncoupling of snRNPs from SMA. Recent report.

This paper is now freely available in PubMed Central.

Praveen K, Wen Y, Matera AG. A Drosophila model of spinal muscular atrophy uncouples snRNP biogenesis functions of survival motor neuron from locomotion and viability defects. Cell Rep. 2012 Jun 28;1(6):624-31. PMID: 22813737; PMCID: PMC3405901.

From the abstract: "These findings have major implications for SMA etiology because they show that SMN's role in snRNP biogenesis can be uncoupled from the organismal viability and locomotor defects."

See also this posted paper on splicing & SMA.
Or all blog posts on SMA.

Fly models & Alzheimers. Recent report.

Hopkins PC. Neurodegeneration in a Drosophila Model for the Function of TMCC2, an Amyloid Protein Precursor-Interacting and Apolipoprotein E-Binding Protein. PLoS One. 2013;8(2):e55810. doi: 10.1371/journal.pone.0055810. PubMed PMID: 23409049; PubMed Central PMCID: PMC3567013.

Aiming to kill mosquitoes, not flies (or people). Recent Report.

The health relevance of Drosophila as a model system extends beyond conserved human genes. This report describes testing compounds in mosquito, Drosophila and human cells in an effort to identify compounds that kill mosquitoes without affecting related insects like fruit flies, or humans.

O'Neal MA, Posner BA, Coates CJ, Abrams JM. A Cell-Based Screening Platform Identifies Novel Mosquitocidal Toxins. J Biomol Screen. 2013 Feb 13. PubMed PMID: 23407365.

Thursday, February 21, 2013

Cardiomyopathies & the fly. Recent review.

This review provides background on key aspects of using Drosophila as a model system and discusses how the fly can be used to model cardiomyopathies. See especially Fig. 2.

From the review: "Drosophila genetics provides a powerful system to identify genes and pathways that potentially contribute to cardiomyopathies and serves as a platform to validate candidate human polymorphisms associated with cardiomyopathies."

Wolf MJ. Modeling dilated cardiomyopathies in Drosophila. Trends Cardiovasc Med. 2012 Apr;22(3):55-61. doi: 10.1016/j.tcm.2012.06.012. PubMed PMID: 22863366.

Tuesday, February 12, 2013

LRRK2 and PD. Recent reports.

Macleod DA, Rhinn H, Kuwahara T, Zolin A, Di Paolo G, Maccabe BD, Marder KS, Honig LS, Clark LN, Small SA, Abeliovich A. RAB7L1 Interacts with LRRK2 to Modify Intraneuronal Protein Sorting and Parkinson's Disease Risk. Neuron. 2013 Feb 6;77(3):425-39. doi: 10.1016/j.neuron.2012.11.033. PubMed PMID: 23395371.

From the Abstract:  "Deficiency of the PARK16 locus gene RAB7L1 in primary rodent neurons, or of a RAB7L1 ortholog in Drosophila dopamine neurons, recapitulated degeneration observed with expression of a familial PD mutant form of LRRK2, whereas RAB7L1 overexpression rescued the LRRK2 mutant phenotypes."


Hindle S, Afsari F, Stark M, Middleton CA, Evans GJ, Sweeney ST, Elliott CJ. Dopaminergic expression of the Parkinsonian gene LRRK2-G2019S leads to non-autonomous visual neurodegeneration, accelerated by increased neural demands for energy. Hum Mol Genet. 2013 Feb 7. PubMed PMID: 23396536.

From the abstract:  "We investigated the effect of LRRK2 mutations (the most common cause of inherited PD) on Drosophila electroretinograms (ERGs). We reveal progressive loss of photoreceptor function in flies expressing LRRK2-G2019S in dopaminergic neurons."

Monday, February 11, 2013

X-linked Infantile Spinal Muscular Atrophy. Fly model. Recent report.

Liu HY, Pfleger CM. Mutation in e1, the ubiquitin activating enzyme, reduces Drosophila lifespan and results in motor impairment. PLoS One. 2013;8(1):e32835. doi: 10.1371/journal.pone.0032835. Epub 2013 Jan 29. PubMed PMID: 23382794; PubMed Central PMCID: PMC3558519.

High-throughput compound screen with follow-up in fly model. Relevance to Alzheimer's disease. Recent report.

McKoy AF, Chen J, Schupbach T, Hecht MH. A novel inhibitor of amyloid β (Aβ) peptide aggregation: from high throughput screening to efficacy in an animal model of Alzheimer disease. J Biol Chem. 2012 Nov 9;287(46):38992-9000. PMID: 22992731; PMCID: PMC3493940.

Fly research and malignancy. Recent Review.

This review provides historical perspective and contemporary critique regarding the impact of fly research on understanding cancer biology and developing new treatments.

Gonzalez C. Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics. Nat Rev Cancer. 2013 Feb 7. doi: 10.1038/nrc3461. PubMed PMID: 23388617.

Friday, January 25, 2013

Tau protein and neuronal network hyperexcitability. Fly and mouse model study. Recent report.

Holth JK, Bomben VC, Reed JG, Inoue T, Younkin L, Younkin SG, Pautler RG, Botas J, Noebels JL. Tau loss attenuates neuronal network hyperexcitability in mouse and Drosophila genetic models of epilepsy. J Neurosci. 2013 Jan 23;33(4):1651-9. PubMed PMID: 23345237.

Tuesday, January 22, 2013

Drosophila loss-of-function study of neurodegeneration-associated TDP-43 gene. Recent report.

Vanden Broeck L, Naval-Sánchez M, Adachi Y, Diaper D, Dourlen P, Chapuis J, Kleinberger G, Gistelinck M, Van Broeckhoven C, Lambert JC, Hirth F, Aerts S, Callaerts P, Dermaut B. TDP-43 Loss-of-Function Causes Neuronal Loss Due to Defective Steroid Receptor-Mediated Gene Program Switching in Drosophila. Cell Rep. 2013 Jan 15. doi:pii: S2211-1247(12)00459-7. 10.1016/j.celrep.2012.12.014.PubMed PMID: 23333275.

Protein granules in fly model of Fragile X. Recent report.

Gareau C, Martel D, Coudert L, Mellaoui S, Mazroui R. Characterization of Fragile X Mental Retardation Protein granules formation and dynamics in Drosophila. Biol Open. 2013 Jan 15;2(1):68-81. PubMed PMID: 23336078.

Wednesday, January 16, 2013

Loss versus gain of TDP-43 study. Recent report.

Diaper DC, Adachi Y, Sutcliffe B, Humphrey DM, Elliott CJ, Stepto A, Ludlow ZN, Broeck LV, Callaerts P, Dermaut B, Al-Chalabi A, Shaw CE, Robinson IM, Hirth F. Loss and gain of Drosophila TDP-43 impair synaptic efficacy and motor control leading to age-related neurodegeneration by loss-of-function phenotypes. Hum Mol Genet. 2013 Jan 10. PMID: 23307927.

Leaf extract test with fly model of Parkinson's disease. Recent report.

Siddique YH, Mujtaba SF, Jyoti S, Naz F. GC-MS analysis of Eucalyptus citriodora leaf extract and its role on the dietary supplementation in transgenic Drosophila model of Parkinson's disease. Food Chem Toxicol. 2013 Jan 11. doi:pii: S0278-6915(12)00901-5. 10.1016/j.fct.2012.12.028. PubMed PMID: 23318758.

Evidence that beta blockers extend life in mice and flies. Recent report.

Spindler SR, Mote PL, Li R, Dhahbi JM, Yamakawa A, Flegal JM, Jeske DR, Li R, Lublin AL. β1-Adrenergic receptor blockade extends the life span of Drosophila and long-lived mice. Age (Dordr). 2013 Jan 15. PubMed PMID: 23314750.

Parallel mouse and fly study points to EGFR target in A-beta-mediated memory loss. Recent report.

Wang L, Chiang HC, Wu W, Liang B, Xie Z, Yao X, Ma W, Du S, Zhong Y. Epidermal growth factor receptor is a preferred target for treating amyloid-β-induced memory loss. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16743-8. doi: 10.1073/pnas.1208011109. PubMed PMID: 23019586; PubMed Central PMCID: PMC3478595.

Saturday, January 12, 2013

Tick-borne pathogen studied in fly. Recent report.

Drosophila has been called "the model model organism" as it can be used not only as a model of human diseases and pathways but also as a model of arthropod pests and disease vectors.

In the introduction of this paper the authors state that "Although genetic tools for working with ticks are currently being developed (Pagel Van Zee et al., 2007), the available tools do not begin to approach those that are available in other arthropods such as Drosophila melanogaster."

Drolia R, Von Ohlen T, Chapes SK. Ehrlichia chaffeensis replication sites in adult Drosophila melanogaster. Int J Med Microbiol. 2013 Jan 7. doi:pii: 1438-4221(12)00094-X. PMID: 23306065.

E. chaffeensis is the causitive agent of the tick-borne disease human monocytic ehrlichiosis. You can read about this disease online at the NORD website.

Friday, January 11, 2013

Studying obesity in model systems. Recent review.

From the abstract: "... we searched biological databases and discovered 33 additional genes associated with human obesity ... We find that the majority have orthologues in distant species, such as D. melanogaster ..." DIOPT finds additional putative fly orthologs not listed in their Table 1.

Williams MJ, Almén MS, Fredriksson R, Schiöth HB. What model organisms and interactomics can reveal about the genetics of human obesity. Cell Mol Life Sci. 2012 Nov;69(22):3819-34. doi: 10.1007/s00018-012-1022-5. Review. PubMed PMID: 22618246.

Wednesday, January 9, 2013

Disease-associated mutations in Actin. New fly models. Recent report.

These authors report introducing six different mutant forms of actin associated with myopathies in humans into the fly indirect flight muscle, as well as characterization of the resulting phenotypes.

Sevdali M, Kumar V, Peckham M, Sparrow J. Human congenital myopathy actin mutants cause myopathy and alter Z-disc structure in Drosophila flight muscle. Neuromuscul Disord. 2013 Jan 4. doi:pii: S0960-8966(12)00698-0. 10.1016/j.nmd.2012.11.013. PMID: 23294764.

Tuesday, January 8, 2013

Why not work on ... ?

The human gene TMCO1 ("transmembrane and coiled-coil domains 1") is associated with "Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome" (NCBI OMIM Entry 614132). The summary at NCBI Entrez Gene suggests the gene is also associated with "open angle glaucoma blindness" (it  looks like this is based on GWAS data).

The fly gene CG10470 scores a 10 out of 10 for ortholog match to TMCO1 (i.e. 10 out of 10 tools/algorithms represented at DIOPT predict an ortholog relationship between TMCO1 and CG10470). Screenshots of the DIOPT-DIST results and alignment are shown below.

Currently, it looks like little is known about the normal function of the human or fly genes. Will you be the person who sheds light on function of this disease-relevant gene?

Monday, January 7, 2013

Flies and fish contribute to study on SMA. Recent report.

Lotti F, Imlach WL, Saieva L, Beck ES, Hao le T, Li DK, Jiao W, Mentis GZ, Beattie CE, McCabe BD, Pellizzoni L. An SMN-dependent U12 splicing event essential for motor circuit function. Cell. 2012 Oct 12;151(2):440-54. doi: 10.1016/j.cell.2012.09.012. PubMed PMID: 23063131; PubMed Central PMCID: PMC3474596.

Fly eye assay included in leukemia study. Recent report.

Expression of the Notch signaling ligand Delta in the fly eye creates a sensitized background exploited as part of follow-up on gene identified in this exome sequencing study aimed at understanding T-cell acute lymphoblastic leukemia.

De Keersmaecker K, Atak ZK, Li N, Vicente C, Patchett S, Girardi T, Gianfelici V, Geerdens E, Clappier E, Porcu M, Lahortiga I, Lucà R, Yan J, Hulselmans G, Vranckx H, Vandepoel R, Sweron B, Jacobs K, Mentens N, Wlodarska I, Cauwelier B, Cloos J, Soulier J, Uyttebroeck A, Bagni C, Hassan BA, Vandenberghe P, Johnson AW, Aerts S, Cools J. Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. Nat Genet. 2012 Dec 23. doi: 10.1038/ng.2508. PMID: 23263491.

Lipids & the fly. Recent review.

Liu Z, Huang X. Lipid metabolism in Drosophila: development and disease. Acta Biochim Biophys Sin (Shanghai). 2013 Jan;45(1):44-50. doi: 10.1093/abbs/gms105. PMID: 23257293.

From the abstract: "Some recent progresses of lipid metabolic regulation during Drosophila development and in Drosophila models of human diseases will be discussed in this review."

Ortholog search tools updated

A 10th tool, OrthoDB, has now been incorporated into results from the DIOPT and DIOPT-DIST tools for ortholog identification, including disease gene ortholog identification. Check it out.