Sneak peak--'facelift' to DRSC website including our disease gene ortholog tool

We are undertaking a modest 'face lift' and update to our DRSC website.

Of interest to blog readers--one of the tools we're updating in look is our DIOPT-DIST resource.

DIOPT-DIST associates a fly gene (or other model species gene) with putative human orthologs, and also associates human orthologs with disease information (from OMIM or public GWAS data).

Here's a sneak peak of our new look. As of this post, the links will take you to our original pages, but be on the lookout for the updated look soon! Feedback welcome, now as always.

Here's the original publication describing DIOPT and DIOPT-DIST -- since updated to include an additional ortholog search algorithm and two more model species.

Hu Y, Flockhart I, Vinayagam A, Bergwitz C, Berger B, Perrimon N, Mohr SE. An integrative approach to ortholog prediction for disease-focused and other functional studies. BMC Bioinformatics. 2011 Aug 31;12:357. PMID: 21880147

It's a BioMed Central 'Highly Accessed' publication and is freely available at PMC.

A call for "a better collaboration between Drosophila geneticists/biologists and human geneticists/ bioinformaticians/clinicians"

Wangler MF, Yamamoto S, Bellen HJ. Fruit Flies in Biomedical Research. Genetics. 2015 Jan 26. pii: genetics.114.171785. PMID: 25624315.

From the abstract: "... numerous very interesting biological processes and avenues remain to be investigated in Drosophila, and probing questions can be answered fast and efficiently in flies ... We would like to promote a better collaboration between Drosophila geneticists/biologists and human geneticists/bioinformaticians/clinicians, as it would benefit both fields and significantly impact the research on human diseases."

Drosophila genetic analysis contributes to study on Gordon Holmes syndrome (GDHS)

Topaloglu AK, Lomniczi A, Kretzschmar D, Dissen GA, Kotan LD, McArdle CA, Koc AF, Hamel BC, Guclu M, Papatya ED, Eren E, Mengen E, Gurbuz F, Cook M, Castellano JM, Kekil MB, Mungan NO, Yuksel B, Ojeda SR. Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome. J Clin Endocrinol Metab. 2014 Oct;99(10):E2067-75. PMID: 25033069.

From the abstract:  "... We identified 6 patients from 3 independent families carrying loss-of-function mutations in PNPLA6, which encodes neuropathy target esterase (NTE) ... Wild-type PNPLA6, but not PNPLA6 bearing these mutations, rescued a well-established Drosophila neurodegenerative phenotype caused by the absence of sws, the fly ortholog of mammalian PNPLA6. ..."

Review written for clinicians and mammalian researchers about non-mammalian models of epilepsy

Cunliffe VT, Baines RA, Giachello CN, Lin WH, Morgan A, Reuber M, Russell C, Walker MC, Williams RS. Epilepsy research methods update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms. Seizure. 2014 Oct 13. PMID: 25457452.

From the abstract:  "This narrative review is intended to introduce clinicians treating epilepsy and researchers familiar with mammalian models of epilepsy to experimentally tractable, non-mammalian research models used in epilepsy research, ranging from unicellular eukaryotes to more complex multicellular organisms. The review focuses on four model organisms: the social amoeba Dictyostelium discoideum, the roundworm Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the zebrafish Danio rerio. ..."

Drosophila model of triosephosphate isomerase (TPI) deficiency

Roland BP, Amrich CG, Kammerer CJ, Stuchul KA, Larsen SB, Rode S, Aslam AA, Heroux A, Wetzel R, VanDemark AP, Palladino MJ. Triosephosphate isomerase I170V alters catalytic site, enhances stability and induces pathology in a Drosophila model of TPI deficiency. Biochim Biophys Acta. 2015 Jan;1852(1):61-9. PMID: 25463631.

Neurodegenerative models--catching up

Catching up on recent papers related to Drosophila as a model for neurodegenerative diseases.

Fernandes AC, Uytterhoeven V, Kuenen S, Wang YC, Slabbaert JR, Swerts J, Kasprowicz J, Aerts S, Verstreken P. Reduced synaptic vesicle protein degradation at lysosomes curbs TBC1D24/sky-induced neurodegeneration. J Cell Biol. 2014 Nov 24;207(4):453-62. PMID: 25422373; PMCID: PMC4242831. From the abstract: "In this paper, we study Drosophila melanogaster lacking active TBC1D24/Skywalker (Sky), a protein that in humans causes severe neurodegeneration, epilepsy, and DOOR (deafness, onychdystrophy, osteodystrophy, and mental retardation) syndrome, ... Using chimeric fluorescent timers, we show that synaptic vesicle-associated proteins were younger on average ... Using a genetic screen, we find that reducing endosomal-to-lysosomal trafficking ... rescued the neurotransmission and neurodegeneration defects in sky mutants. ... Our findings define a mechanism in which synaptic transmission is facilitated by efficient protein turnover at lysosomes and identify a potential strategy to suppress defects arising from TBC1D24 mutations in humans. "

Vanden Broeck L, Kleinberger G, Chapuis J, Gistelinck M, Amouyel P, Van Broeckhoven C, Lambert JC, Callaerts P, Dermaut B. Functional complementation in Drosophila to predict the pathogenicity of TARDBP variants: evidence for a loss-of-function mechanism. Neurobiol Aging. 2014 Sep 28. pii: S0197-4580(14)00596-X. PMID: 25442115.

Jäckel S, Summerer AK, Thömmes CM, Pan X, Voigt A, Schulz JB, Rasse TM, Dormann D, Haass C, Kahle PJ. Nuclear import factor transportin and arginine methyltransferase 1 modify FUS neurotoxicity in Drosophila. Neurobiol Dis. 2014 Nov 8;74C:76-88. PMID: 25447237. From the abstract: "... To investigate the requirements for the nuclear import of FUS in an in vivo model, we generated different transgenic Drosophila lines expressing human FUS wild type (hFUS wt) and two disease-related variants P525L and R495X, in which the NLS is mutated or completely absent, respectively. ..."

Pogson JH, Ivatt RM, Sanchez-Martinez A, Tufi R, Wilson E, Mortiboys H, Whitworth AJ. The Complex I Subunit NDUFA10 Selectively Rescues Drosophila pink1 Mutants through a Mechanism Independent of Mitophagy. PLoS Genet. 2014 Nov 20;10(11):e1004815. doi: 10.1371/journal.pgen.1004815. PMID: 25412178; PMCID: PMC4238976.

Jahromi SR, Haddadi M, Shivanandappa T, Ramesh SR. Modulatory effect of Decalepis hamiltonii on ethanol-induced toxicity in transgenic Drosophila model of Parkinson's disease. Neurochem Int. 2014 Nov 5;80C:1-6. doi: PMID: 25451756.

Siddique YH, Faisal M, Naz F, Jyoti S, Rahul. Role of Ocimum sanctum leaf extract on dietary supplementation in the transgenic Drosophila model of Parkinson's disease. Chin J Nat Med. 2014 Oct;12(10):777-81. PMID: 25443371.

Could custom fly cell lines help your disease model-related research? See post at FlyRNAi.

FlyRNAi: Thinking ahead--What could custom CRISPR engineere...: Open call to the Drosophila research community from the DRSC : Since it was founded in 2003 by Prof. N. Perrimon, the Drosophila RNAi Sc...