Friday, December 21, 2018

Top ten posts at Drosophila Models of Human Diseases

Celebrating the year's end with a list of the most-viewed blog posts:

If it sickens flies, do I want it in me? Using Drosophila to assess toxicity of plant extracts









And the most-viewed post of all time (as of December 2018):
Results from Drosophila contribute to study of the neurodevelopmental disorder Vici syndrome

Diet and the gut

Pereira MT, Malik M, Nostro JA, Mahler GJ, Musselman LP. Effect of dietary additives on intestinal permeability in both Drosophila and a human cell co-culture. Dis Model Mech. 2018 Nov 28;11(12). pii: dmm034520. PMID: 30504122.

From the abstract: "Increased intestinal barrier permeability has been correlated with aging and disease, including type 2 diabetes, Crohn's disease, celiac disease, multiple sclerosis and irritable bowel syndrome. The prevalence of these ailments has risen together with an increase in industrial food processing and food additive consumption. Additives, including sugar, metal oxide nanoparticles, surfactants and sodium chloride, have all been suggested to increase intestinal permeability. We used two complementary model systems to examine the effects of food additives on gut barrier function: a Drosophila in vivo model and an in vitro human cell co-culture model. ... This study extends previous work in flies and humans showing that diet can play a role in the health of the gut barrier. ..."

Genetic models of Parkinson's disease -- review article and database

Breger LS, Fuzzati Armentero MT. Genetically engineered animal models of Parkinson's disease: from worm to rodent. Eur J Neurosci. 2018 Dec 14. PMID: 30552719.

From the abstract: "Parkinson's disease (PD) is a progressive neurological disorder ... The EU Joint Programme - Neurodegenerative Disease Research (JPND) has promoted the creation of an online database aiming at summarising the different features of experimental models of Parkinson's disease. This review discusses available genetic models of PD and the extent to which they adequately mirror the human pathology ..."

Circadian rhythms, Parkinson's disease, and fruit fly research

De Lazzari F, Bisaglia M, Zordan MA, Sandrelli F. Circadian Rhythm Abnormalities in Parkinson's Disease from Humans to Flies and Back. Int J Mol Sci. 2018 Dec 6;19(12). pii: E3911. PMID: 30563246.

From the abstract: "Clinical and research studies have suggested a link between Parkinson's disease (PD) and alterations in the circadian clock. Drosophila melanogaster may represent a useful model to study the relationship between the circadian clock and PD. ... Here, we describe the fly circadian and dopaminergic systems and report recent studies which indicate the presence of circadian abnormalities in some fly PD genetic models. We discuss the use of Drosophila to investigate whether, in adults, the disruption of the circadian system might be causative of brain neurodegeneration. We also consider approaches using Drosophila, which might provide new information ... As a corollary, ... we suggest that genetic models of PD could be used to perform lifelong screens for drug-modulators of general and/or circadian-related PD traits."

Drosophila as "providing an unparalleled opportunity to combine dietary manipulation with models of human metabolic disease and cancer" (Review Article)

Warr CG, Shaw KH, Azim A, Piper MDW, Parsons LM. Using Mouse and Drosophila Models to Investigate the Mechanistic Links between Diet, Obesity, Type II Diabetes, and Cancer. Int J Mol Sci. 2018 Dec 18;19(12). pii: E4110. PMID: 30567377.

The abstract: "Many of the links between diet and cancer are controversial and over simplified. To date, human epidemiological studies consistently reveal that patients who suffer diet-related obesity and/or type II diabetes have an increased risk of cancer, suffer more aggressive cancers, and respond poorly to current therapies. However, the underlying molecular mechanisms that increase cancer risk and decrease the response to cancer therapies in these patients remain largely unknown. Here, we review studies in mouse cancer models in which either dietary or genetic manipulation has been used to model obesity and/or type II diabetes. These studies demonstrate an emerging role for the conserved insulin and insulin-like growth factor signaling pathways as links between diet and cancer progression. However, these models are time consuming to develop and expensive to maintain. As the world faces an epidemic of obesity and type II diabetes we argue that the development of novel animal models is urgently required. We make the case for Drosophila as providing an unparalleled opportunity to combine dietary manipulation with models of human metabolic disease and cancer. Thus, combining diet and cancer models in Drosophila can rapidly and significantly advance our understanding of the conserved molecular mechanisms that link diet and diet-related metabolic disorders to poor cancer patient prognosis."

Friday, December 14, 2018

Studies in Drosophila help reveal how Dengue and Zika virus cause disease

Shah, et al. (2018) Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms of Dengue and Zika Virus Pathogenesis. Cell 175(7):1931-1945.e18

Graphical abstract for this report in Cell
from the Bellen, Andino, & Krogan labs
Summary: "Mosquito-borne flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), are a growing public health concern. Systems-level analysis of how flaviviruses hijack cellular processes through virus-host protein-protein interactions (PPIs) provides information about their replication and pathogenic mechanisms. We used affinity purification-mass spectrometry (AP-MS) to compare flavivirus-host interactions for two viruses (DENV and ZIKV) in two hosts (human and mosquito). Conserved virus-host PPIs revealed that the flavivirus NS5 protein suppresses interferon stimulated genes by inhibiting recruitment of the transcription complex PAF1C and that chemical modulation of SEC61 inhibits DENV and ZIKV replication in human and mosquito cells. Finally, we identified a ZIKV-specific interaction between NS4A and ANKLE2, a gene linked to hereditary microcephaly, and showed that ZIKV NS4A causes microcephaly in Drosophila in an ANKLE2-dependent manner. Thus, comparative flavivirus-host PPI mapping provides biological insights and, when coupled with in vivo models, can be used to unravel pathogenic mechanisms."

Note: when available from PubMed, the full author list and PubMed ID will be added.

Wednesday, November 21, 2018

... and another! Fly study helps point to possible genetic cause of an ARID

Kazeminasab S, Taskiran II, Fattahi Z, Bazazzadegan N, Hosseini M, Rahimi M, Oladnabi M, Haddadi M, Celik A, Ropers HH, Najmabadi H, Kahrizi K. CNKSR1 gene defect can cause syndromic autosomal recessive intellectual disability. Am J Med Genet B Neuropsychiatr Genet. 2018 Nov 18. doi: 10.1002/ajmg.b.32648. PMID: 30450701.

From the abstract: "... A novel frameshift mutation in CNKSR1 gene was detected by Next-Generation Sequencing (NGS) in an Iranian family with syndromic autosomal recessive intellectual disability (ARID). CNKSR1 encodes a connector enhancer of kinase suppressor of Ras 1 ... CNKSR1 interacts with proteins which have already been shown to be associated with intellectual disability (ID) in the MAPK signaling pathway and promotes cell migration through RhoA-mediated c-Jun N-terminal kinase (JNK) activation. Lack of CNKSR1 transcripts and protein was observed in lymphoblastoid cells derived from affected patients using qRT-PCR and western blot analysis ...  RNAi-mediated knockdown of cnk, the CNKSR1 orthologue in Drosophila melanogaster brain, led to defects in eye and mushroom body (MB) structures. In conclusion, our findings support the possible role of CNKSR1 in brain development which can lead to cognitive impairment."