Targeting Imd pathway receptor in Drosophila melanogaster and repurposing of phyto-inhibitors: structural modulation and molecular dynamics

2020 ◽  
pp. 1-12
Author(s):  
Pankaj Satapathy ◽  
Jeevan Kallur Prakash ◽  
V. Chirag Gowda ◽  
Sunil S. More ◽  
Muthuchelian K ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Drosophila Melanogaster ◽  
Imd Pathway ◽  
Structural Modulation

scholarly journals Drosophila melanogaster as a Model System to Assess the Effect of Epstein-Barr Virus DNA on Inflammatory Gut Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Joelle R. Madi ◽  
Amani Al Outa ◽  
Mirna Ghannam ◽  
Hadi M. Hussein ◽  
Marwa Shehab ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Epstein Barr Virus ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Sulfated Polysaccharide ◽  
Intestinal Damage ◽  
Barr Virus ◽  
Imd Pathway ◽  
Ebv Dna ◽  
Epstein Barr

The Epstein-Barr virus (EBV) commonly infects humans and is highly associated with different types of cancers and autoimmune diseases. EBV has also been detected in inflamed gastrointestinal mucosa of patients suffering from prolonged inflammation of the digestive tract such as inflammatory bowel disease (IBD) with no clear role identified yet for EBV in the pathology of such diseases. Since we have previously reported immune-stimulating capabilities of EBV DNA in various models, in this study we investigated whether EBV DNA may play a role in exacerbating intestinal inflammation through innate immune and regeneration responses using the Drosophila melanogaster model. We have generated inflamed gastrointestinal tracts in adult fruit flies through the administration of dextran sodium sulfate (DSS), a sulfated polysaccharide that causes human ulcerative colitis- like pathologies due to its toxicity to intestinal cells. Intestinal damage induced by inflammation recruited plasmatocytes to the ileum in fly hindguts. EBV DNA aggravated inflammation by enhancing the immune deficiency (IMD) pathway as well as further increasing the cellular inflammatory responses manifested upon the administration of DSS. The study at hand proposes a possible immunostimulatory role of the viral DNA exerted specifically in the fly hindgut hence further developing our understanding of immune responses mounted against EBV DNA in the latter intestinal segment of the D. melanogaster gut. These findings suggest that EBV DNA may perpetuate proinflammatory processes initiated in an inflamed digestive system. Our findings indicate that D. melanogaster can serve as a model to further understand EBV-associated gastroinflammatory pathologies. Further studies employing mammalian models may validate the immunogenicity of EBV DNA in an IBD context and its role in exacerbating the disease through inflammatory mediators.

scholarly journals Disparate regulation of imd drives sex differences in infection pathology in Drosophila melanogaster

2020 ◽  
Author(s):  
Crystal M. Vincent ◽  
Marc S. Dionne
Keyword(s):  
Drosophila Melanogaster ◽  
Negative Regulator ◽  
Sexually Dimorphic ◽  
Wild Type ◽  
Functional Importance ◽  
Male And Female ◽  
Immune Activity ◽  
Imd Pathway ◽  
Independent Effects ◽  
Female Specific

AbstractMale and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is sex-specific costs of immune activity or pathology, but little is known about the independent effects of immune-induced versus microbe-induced pathology, and whether these may differ for the sexes. Here, through measuring metabolic and physiological outputs in wild-type and immune-compromised Drosophila melanogaster, we test whether the sexes are differentially impacted by these various sources of pathology and identify a critical regulator of this difference. We find that the sexes exhibit differential immune activity but similar bacteria-derived metabolic pathology. We show that female-specific immune-inducible expression of PGRP-LB, a negative regulator of the Imd pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence of PGRP-LB, females are more resistant of infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost.

MODELLING OF POLYCOMB-DEPENDENT CHROMOSOMAL INTERACTIONS INVOLVED IN DROSOPHILA GENE SILENCING

2006 ◽  
Vol 17 (05) ◽  
pp. 757-767
Author(s):  
SILKE RITTER ◽  
JENS ODENHEIMER ◽  
DIETER W. HEERMANN ◽  
FREDERIC BANTIGNIES ◽  
CHARLOTTE GRIMAUD ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Drosophila Melanogaster ◽  
Gene Silencing ◽  
Polymer Chains ◽  
Segment Length ◽  
Kuhn Segment ◽  
End Points ◽  
Wall Distance ◽  
Repulsive Forces ◽  
Kuhn Segment Length

The conditions of the chromosomes inside the nucleus in the Rabl configuration have been modelled as self-avoiding polymer chains under restraining conditions. To ensure that the chromosomes remain stretched out and lined up, we fixed their end points to two opposing walls. The numbers of segments N, the distances d1 and d2 between the fixpoints, and the wall-to-wall distance z (as measured in segment lengths) determine an approximate value for the Kuhn segment length kl. We have simulated the movement of the chromosomes using molecular dynamics to obtain the expected distance distribution between the genetic loci in the absence of further attractive or repulsive forces. A comparison to biological experiments on Drosophila Melanogaster yields information on the parameters for our model. With the correct parameters it is possible to draw conclusions on the strength and range of the attraction that leads to pairing.

scholarly journals Motor domain phosphorylation and regulation of the Drosophila kinesin 13, KLP10A

2009 ◽  
Vol 186 (4) ◽  
pp. 481-490 ◽  
Author(s):  
Vito Mennella ◽  
Dong-Yan Tan ◽  
Daniel W. Buster ◽  
Ana B. Asenjo ◽  
Uttama Rath ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cell Cycle ◽  
Molecular Dynamics ◽  
Drosophila Melanogaster ◽  
Structural Features ◽  
Motor Domain ◽  
Α Helix ◽  
Dynamics Simulations

Microtubule (MT)-destabilizing kinesin 13s perform fundamental roles throughout the cell cycle. In this study, we show that the Drosophila melanogaster kinesin 13, KLP10A, is phosphorylated in vivo at a conserved serine (S573) positioned within the α-helix 5 of the motor domain. In vitro, a phosphomimic KLP10A S573E mutant displays a reduced capacity to depolymerize MTs but normal affinity for the MT lattice. In cells, replacement of endogenous KLP10A with KLP10A S573E dampens MT plus end dynamics throughout the cell cycle, whereas a nonphosphorylatable S573A mutant apparently enhances activity during mitosis. Electron microscopy suggests that KLP10A S573 phosphorylation alters its association with the MT lattice, whereas molecular dynamics simulations reveal how KLP10A phosphorylation can alter the kinesin–MT interface without changing important structural features within the motor’s core. Finally, we identify casein kinase 1α as a possible candidate for KLP10A phosphorylation. We propose a model in which phosphorylation of the KLP10A motor domain provides a regulatory switch controlling the time and place of MT depolymerization.

MODELLING OF POLYCOMB-DEPENDENT CHROMOSOMAL INTERACTIONS INVOLVED IN DROSOPHILA GENE SILENCING

2006 ◽  
Vol 01 (02) ◽  
pp. 141-151
Author(s):  
SILKE RITTER ◽  
JENS ODENHEIMER ◽  
DIETER W. HEERMANN ◽  
FREDERIC BANTIGNIES ◽  
CHARLOTTE GRIMAUD ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Drosophila Melanogaster ◽  
Gene Silencing ◽  
Polymer Chains ◽  
Segment Length ◽  
Kuhn Segment ◽  
End Points ◽  
Wall Distance ◽  
Repulsive Forces ◽  
Kuhn Segment Length

The conditions of the chromosomes inside the nucleus in the Rabl configuration have been modelled as self-avoiding polymer chains under restraining conditions. To ensure that the chromosomes remain stretched out and lined up, we fixed their end points to two opposing walls. The numbers of segments N, the distances d1 and d2 between the fixpoints, and the wall-to-wall distance z (as measured in segment lengths) determine an approximate value for the Kuhn segment length kl. We have simulated the movement of the chromosomes using molecular dynamics to obtain the expected distance distribution between the genetic loci in the absence of further attractive or repulsive forces. A comparison to biological experiments on Drosophila Melanogaster yields information on the parameters for our model. With the correct parameters it is possible to draw conclusions on the strength and range of the attraction that leads to pairing.

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