Tuesday, January 24, 2017

Results of a study in Drosophila suggest the possible relevance of neuronal aneuploidy to Tau-associated neurodegeneration

Malmanche N, Dourlen P, Gistelinck M, Demiautte F, Link N, Dupont C, Vanden Broeck L, Werkmeister E, Amouyel P, Bongiovanni A, Bauderlique H, Moechars D, Royou A, Bellen HJ, Lafont F, Callaerts P, Lambert JC, Dermaut B. Developmental Expression of 4-Repeat-Tau Induces Neuronal Aneuploidy in Drosophila Tauopathy Models. Sci Rep. 2017 Jan 23;7:40764. PMID: 28112163.

From the abstract: "Tau-mediated neurodegeneration in Alzheimer's disease and tauopathies is generally assumed to start in a normally developed brain. However, several lines of evidence suggest that impaired Tau isoform expression during development could affect mitosis and ploidy in post-mitotic differentiated tissue. ... Here, we used genetic and cellular tools to study the link between 3R and 4R-Tau isoform expression, mitotic progression in neuronal progenitors and post-mitotic neuronal survival. Our results illustrated that the severity of Tau-induced adult phenotypes depends on 4R-Tau isoform expression during development. ... we found a high level of aneuploidy in post-mitotic differentiated tissue. ... our results suggested that neurodegeneration could be in part linked to neuronal aneuploidy caused by 4R-Tau expression during brain development."

Monday, January 23, 2017

Using flies to functionally validate candidate heart disease-related genes

Zhu JY, Fu Y, Nettleton M, Richman A, Han Z. High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila. Elife. 2017 Jan 13;6. pii: e22617. PMID: 28084990.

From the abstract: "... We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenital Heart Disease (CHD) patients. 134 genes were tested in the Drosophila heart using RNAi-based gene silencing. Quantitative analyses of multiple cardiac phenotypes demonstrated essential structural, functional, and developmental roles for more than 70 genes ... We also demonstrated the use of Drosophila to evaluate cardiac phenotypes resulting from specific, patient-derived alleles of candidate disease genes. ... This approach has the potential to facilitate development of precision medicine approaches for CHD and other diseases associated with genetic factors."

Review of drug discovery using model organisms including Drosophila

Strange K. Drug Discovery in Fish, Flies, and Worms. ILAR J. 2016 Dec;57(2):133-143. PMID: 28053067.

From the abstract: "Nonmammalian model organisms ... provide numerous experimental advantages for drug discovery including genetic and molecular tractability, amenability to high-throughput screening methods and reduced experimental costs and increased experimental throughput compared to traditional mammalian models. ... This review will provide an overview of C. elegans, Drosophila, and zebrafish biology and husbandry and will discuss how these models are being used for phenotype-based drug screening and for identification of drug targets and mechanisms of action. ..."

Wednesday, January 11, 2017

Modified fly cultured cells as a biotherapeutic? Study suggests this could one day be an effective approach

Roy DG, Power AT, Bourgeois-Daigneault MC, Falls T, Ferreira L, Stern A, Tanese de Souza C, McCart JA, Stojdl DF, Lichty BD, Atkins H, Auer RC, Bell JC, Le Boeuf F. Programmable insect cell carriers for systemic delivery of integrated cancer biotherapy. J Control Release. 2015 Dec 28;220(Pt A):210-21. PMID: 26482080.

From the abstract: "Due to cancer's genetic complexity, significant advances in the treatment of metastatic disease will require sophisticated, multi-pronged therapeutic approaches. Here we demonstrate the utility of a Drosophila melanogaster cell platform for the production and in vivo delivery of multi-gene biotherapeutic systems. We show that cultured Drosophila S2 cell carriers can stably propagate oncolytic viral therapeutics that are highly cytotoxic for mammalian cancer cells without adverse effects on insect cell viability or gene expression. Drosophila cell carriers administered systemically to immunocompetent animals trafficked to tumors to deliver multiple biotherapeutics with little apparent off-target tissue homing or toxicity, resulting in a therapeutic effect. ..."

Monday, January 9, 2017

Journal issue focuses on fly models of disease

A special issue of Current Topics in Developmental Biology (vol. 121, January 2017) focuses on fly models of human diseases. Check out the journal issue titles to see what specific diseases and disorders are discussed in these expert-level review articles.