Thursday, December 20, 2012

iMAD approach to host-pathogen interaction detection. Recent report.

These authors report a strategy for simultaneous genetic manipulation of the host cell model (Drosophila cells) and pathogen genes (Legionella pneumophila) to identify interactions.

O'Connor TJ, Boyd D, Dorer MS, Isberg RR. Aggravating genetic interactions allow a solution to redundancy in a bacterial pathogen. Science. 2012 Dec 14;338(6113):1440-4. doi: 10.1126/science.1229556. PubMed PMID: 23239729.

Tuesday, December 18, 2012

Lowering A-beta. Recent report.

These authors report a study in flies that led to identification of a conserved protein that is a potential therapeutic target for neurodegenerative disease.

Page RM, Münch A, Horn T, Kuhn PH, Colombo A, Reiner O, Boutros M, Steiner H,
Lichtenthaler SF, Haass C. Loss of PAFAH1B2 Reduces Amyloid-β Generation by Promoting the Degradation of Amyloid Precursor Protein C-Terminal Fragments. J Neurosci. 2012 Dec 12;32(50):18204-18214. PubMed PMID: 23238734.

Monday, December 17, 2012

Pain and the fly. Recent report.

Neely GG, Rao S, Costigan M, Mair N, Racz I, Milinkeviciute G, Meixner A, Nayanala S, Griffin RS, Belfer I, Dai F, Smith S, Diatchenko L, Marengo S, Haubner BJ, Novatchkova M, Gibson D, Maixner W, Pospisilik JA, Hirsch E, Whishaw IQ, Zimmer A, Gupta V, Sasaki J, Kanaho Y, Sasaki T, Kress M, Woolf CJ, Penninger JM. Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception. PLoS Genet. 2012 Dec;8(12):e1003071. doi: 10.1371/journal.pgen.1003071. PMID: 23236288.

ALS study includes tests in new fly models. Recent report.

This study includes report of findings with "a series of transgenic [Drosophila] lines that expressed human WT and mutant EWSR1" developed for the study.

Couthouis J, Hart MP, Erion R, King OD, Diaz Z, Nakaya T, Ibrahim F, Kim HJ, Mojsilovic-Petrovic J, Panossian S, Kim CE, Frackelton EC, Solski JA, Williams KL, Clay-Falcone D, Elman L, McCluskey L, Greene R, Hakonarson H, Kalb RG, Lee VM, Trojanowski JQ, Nicholson GA, Blair IP, Bonini NM, Van Deerlin VM, Mourelatos Z, Shorter J, Gitler AD. Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis. Hum Mol Genet. 2012 Jul 1;21(13):2899-911. PMID: 22454397; PMCID: PMC3373238.

Death, aging and the gut. Recent report.

Rera M, Clark RI, Walker DW. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci U S A. 2012 Dec 12. PMID: 23236133.

Friday, December 14, 2012

LRRK2 in the fly model. Recent report.

These authors report findings with potential impact on treatment of Parkinson's Disease. Use the search box (top right-ish of this page) with "LRRK2" to find additional related posts.

Yang D, Li T, Liu Z, Arbez N, Yan J, Moran TH, Ross CA, Smith WW. LRRK2 kinase activity mediates toxic interactions between genetic mutation and oxidative stress in a Drosophila model: suppression by curcumin. Neurobiol Dis. 2012 Sep;47(3):385-92. doi: 10.1016/j.nbd.2012.05.020. PubMed PMID: 22668778.

Fat flies. New Model. Recent report.

Liu J, Li T, Yang D, Ma R, Moran TH, Smith WW. Synphilin-1 alters metabolic homeostasis in a novel Drosophila obesity model. Int J Obes (Lond). 2012 Dec;36(12):1529-36. doi: 10.1038/ijo.2012.111. PMID: 22828940. Corrigendum: Liu J, Li T, Yang D, Ma R, Moran TH, Smith WW. Synphilin-1 alters metabolic homeostasis in a novel Drosophila obesity model. Int J Obes (Lond). 2012 Dec;36(12):1592. doi: 10.1038/ijo.2012.187. PMID: 23229758.

Animal models of Angelman syndrome. Recent review.

Section five of this freely available article covers fly models of Angelman syndrome. 
 Jana NR. Understanding the pathogenesis of Angelman syndrome through animal models. Neural Plast. 2012;2012:710943. doi: 10.1155/2012/710943. Review. PubMed PMID: 22830052; PubMed Central PMCID: PMC3399338.

Thursday, December 13, 2012

Fumble helps researchers score. Recent review.

This review mentions how research with a fly fumble disease model contributed to the development of potential therapeutic treatments reportedly slated for clinical trial in 2012. Pantothenate kinase-associated neurodegeneration is a type of NBIA.

Hartig MB, Prokisch H, Meitinger T, Klopstock T. Pantothenate kinase-associated neurodegeneration. Curr Drug Targets. 2012 Aug;13(9):1182-9. Review. PMID: 22515741.

"Spiteful behaviour," opportunistic infections & fly model. Recent report.

Lutter EI, Purighalla S, Duong J, Storey DG. Lethality and cooperation of Pseudomonas aeruginosa quorum-sensing mutants in Drosophila melanogaster infection models. Microbiology. 2012 Aug;158(Pt 8):2125-32. doi:10.1099/mic.0.054999-0. PubMed PMID: 22628480.

Check out this YouTube video on P.a. (aimed at a non-expert audience).

Tau oligomers and disease. Recent review.

This recent review includes information from fly and mammalian models.
Cowan CM, Quraishe S, Mudher A. What is the pathological significance of tau oligomers? Biochem Soc Trans. 2012 Aug;40(4):693-7. doi: 10.1042/BST20120135. PMID: 22817718.

Fly polarity genes and cancer. Recent review.

Elsum I, Yates L, Humbert PO, Richardson HE. The Scribble-Dlg-Lgl polarity module in development and cancer: from flies to man. Essays Biochem. 2012;53:141-68. doi: 10.1042/bse0530141. Review. PubMed PMID: 22928514.

Wednesday, December 12, 2012

Mitchondria, Parkinsons and flies. Recent review.

Koh H, Chung J. PINK1 as a molecular checkpoint in the maintenance of mitochondrial function and integrity. Mol Cells. 2012 Jul;34(1):7-13. doi: 10.1007/s10059-012-0100-8. Review. PubMed PMID: 22610403.

Tumor progression. Recent report.

These authors use Drosophila as a model to look at tumor progression. They state that the results "provide a mechanistic basis for interclonal tumour progression driven by mitochondrial dysfunction and oncogenic Ras."

Ohsawa S, Sato Y, Enomoto M, Nakamura M, Betsumiya A, Igaki T. Mitochondrial defect drives non-autonomous tumour progression through Hippo signalling in Drosophila. Nature. 2012 Oct 25;490(7421):547-51. doi: 10.1038/nature11452. PubMed PMID: 23023132.

New fly models for ALS. Recent report.

These authors report "new Drosophila transgenic models expressing a full-length wild-type isoform of human FUS protein" and related findings.

Miguel L, Avequin T, Delarue M, Feuillette S, Frébourg T, Campion D, Lecourtois M. Accumulation of insoluble forms of FUS protein correlates with toxicity in Drosophila. Neurobiol Aging. 2012 May;33(5):1008.e1-15. doi:10.1016/j.neurobiolaging.2011.10.008. PubMed PMID: 22118902.

The aging heart. Recent review.

Kaushik G, Zambon AC, Fuhrmann A, Bernstein SI, Bodmer R, Engler AJ, Cammarato A. Measuring passive myocardial stiffness in Drosophila melanogaster to investigate diastolic dysfunction. J Cell Mol Med. 2012 Aug;16(8):1656-62. doi: 10.1111/j.1582-4934.2011.01517.x. Review. PubMed PMID: 22225769; PubMed Central PMCID: PMC3326184.

Here's one of a few views of the fly beating heard on YouTube.

Fly cancer model used as in vivo test. Recent report.

The authors of this open access study describe using a "validated Drosophila cancer model" to test potential radiosensitizing compounds.

Fu S, Yang Y, Tirtha D, Yen Y, Zhou BS, Zhou MM, Ohlmeyer M, Ko EC, Cagan R, Rosenstein BS, Chen SH, Kao J. γ-H2AX kinetics as a novel approach to high content screening for small molecule radiosensitizers. PLoS One. 2012;7(6):e38465. doi: 10.1371/journal.pone.0038465. PMID: 22768044; PubMed Central PMCID: PMC3387170.

Sunday, December 9, 2012

Potassium channels and alcohol sensitivity. Recent report.

This paper reports investigation into nervous systems functions of the single Drosophila KCNQ-type voltage-gated potassium channel, KCNQ.

Cavaliere S, Gillespie JM, Hodge JJ. KCNQ Channels Show Conserved Ethanol Block and Function in Ethanol Behaviour. PLoS One. 2012;7(11):e50279. doi: 10.1371/journal.pone.0050279. PubMed PMID: 23209695.

Fly stocks used in the study include a Transgenic RNAi Project (TRiP) fly stock targeting KCNQ that is available from the BDSC.

Screenshot of DIOPT-DIST results with fly KCNQ. Click to enlarge.
In the discussion, the authors write that "it is possible that KCNQ might be a candidate gene to predict susceptibility to alcoholism ..." and "... KCNQ openers may offer a potential new approach to treatment of alcohol- and other drug-misuse disorders."

Human KCNQ genes have previously been associated with epilepsy and seizure disorders, including benign familial neonatal seizures.

Thursday, December 6, 2012

Understanding VAPB/vap-33. Recent report.

The authors report investigation into the fly ortholog of VAPB, a human gene that has been linked to ALS, including interaction of the fly VAPB, Vap-33, with Dscam.

Yang Z, Huh SU, Drennan JM, Kathuria H, Martinez JS, Tsuda H, Hall MC, Clemens JC. Drosophila vap-33 is required for axonal localization of dscam isoforms. J Neurosci. 2012 Nov 28;32(48):17241-50. doi: 10.1523/JNEUROSCI.2834-12.2012. PubMed PMID: 23197716.

Wednesday, December 5, 2012

New fly model of hereditary spastic paraplegia. Recent report.

These authors describe a new fly model of HSP. View other posts on HSP here.

Füger P, Sreekumar V, Schüle R, Kern JV, Stanchev DT, Schneider CD, Karle KN, Daub KJ, Siegert VK, Flötenmeyer M, Schwarz H, Schöls L, Rasse TM. Spastic Paraplegia Mutation N256S in the Neuronal Microtubule Motor KIF5A Disrupts Axonal Transport in a Drosophila HSP Model. PLoS Genet. 2012 Nov;8(11):e1003066. doi:10.1371/journal.pgen.1003066. PubMed PMID: 23209432.

Huntington's Disease gene follow-up in the fly. Recent report.

This open access report includes follow-up of mammalian RNAi screen hits in a fly model of Huntington's disease.

Miller JP, Yates BE, Al-Ramahi I, Berman AE, Sanhueza M, Kim E, de Haro M, Degiacomo F, Torcassi C, Holcomb J, Gafni J, Mooney SD, Botas J, Ellerby LM, Hughes RE. A Genome-Scale RNA-Interference Screen Identifies RRAS Signaling as a Pathologic Feature of Huntington's Disease. PLoS Genet. 2012 Nov;8(11):e1003042. doi: 10.1371/journal.pgen.1003042. PubMed PMID: 23209424.

Melioidosis. Virulence in the fly established. Recent report.

This open source paper describes temperature-dependent virulence of the causative agent of melioidosis in the fly. The authors state that the infectious disease melioidosis is problematic in Southeast Asia and Northern Australia.

Pilátová M, Dionne MS. Burkholderia thailandensis Is Virulent in Drosophila melanogaster. PLoS One. 2012;7(11):e49745. doi: 10.1371/journal.pone.0049745.PubMed PMID: 23209596.

Tuesday, December 4, 2012

Guilt by association? Using the FlyAtlas 2 "Profile" feature. Recent report and database update.

This recent report describes updates to the FlyAtlas database of gene expression, including the new web interface FlyAtlas 2.

Robinson SW, Herzyk P, Dow JA, Leader DP. FlyAtlas: database of gene expression in the tissues of Drosophila melanogaster. Nucleic Acids Res. 2012 Nov 29. PubMed PMID: 23203866.

Example results from the FlyAtlas 2 "Profile" Search Tool
The new "Profile" feature might help researchers develop new hypotheses regarding gene function based on the functions of genes with similar expression profiles. To create an example, I picked more or less at random from past posts. I chose the gene Prestin, which is related to kidney stones or nephrolithiasis (view the original post here). A single gene match comes up in this case, CG42365, a gene with unknown function that does not appear to have been evolutionarily conserved. I have searched with a handful of gene names. For most genes I searched, the results came back with between ten and a hundred or so genes with similar profiles to that of my entry gene. If you are trying to understand a human disease gene ortholog, searching at FlyAtlas Profiles might be one of many searches that could help in study design and interpretation.