scholarly journals Author response: Modeling the metabolic interplay between a parasitic worm and its bacterial endosymbiont allows the identification of novel drug targets

2019 ◽  
Author(s):  
David M Curran ◽  
Alexandra Grote ◽  
Nirvana Nursimulu ◽  
Adam Geber ◽  
Dennis Voronin ◽  
...  
Keyword(s):  
Drug Targets ◽  
Author Response ◽  
Bacterial Endosymbiont ◽  
Parasitic Worm ◽  
Response Modeling ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Modeling the metabolic interplay between a parasitic worm and its bacterial endosymbiont allows the identification of novel drug targets

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
David M Curran ◽  
Alexandra Grote ◽  
Nirvana Nursimulu ◽  
Adam Geber ◽  
Dennis Voronin ◽  
...  
Keyword(s):  
Drug Targets ◽  
Metabolic Networks ◽  
Metabolic Model ◽  
Endosymbiotic Bacteria ◽  
Parasitic Worm ◽  
Eukaryotic Organisms ◽  
New Treatments ◽  
Genome Scale ◽  
Novel Drug ◽  
Novel Drug Targets

The filarial nematode Brugia malayi represents a leading cause of disability in the developing world, causing lymphatic filariasis in nearly 40 million people. Currently available drugs are not well-suited to mass drug administration efforts, so new treatments are urgently required. One potential vulnerability is the endosymbiotic bacteria Wolbachia—present in many filariae—which is vital to the worm. Genome scale metabolic networks have been used to study prokaryotes and protists and have proven valuable in identifying therapeutic targets, but have only been applied to multicellular eukaryotic organisms more recently. Here, we present iDC625, the first compartmentalized metabolic model of a parasitic worm. We used this model to show how metabolic pathway usage allows the worm to adapt to different environments, and predict a set of 102 reactions essential to the survival of B. malayi. We validated three of those reactions with drug tests and demonstrated novel antifilarial properties for all three compounds.

scholarly journals Modeling the metabolic interplay between a parasitic worm and its bacterial endosymbiont allows the identification of novel drug targets

2019 ◽  
Author(s):  
DM Curran ◽  
A Grote ◽  
N Nursimulu ◽  
A Geber ◽  
D Voronin ◽  
...  
Keyword(s):  
Drug Targets ◽  
Metabolic Networks ◽  
Metabolic Model ◽  
Endosymbiotic Bacteria ◽  
Parasitic Worm ◽  
Eukaryotic Organisms ◽  
New Treatments ◽  
Genome Scale ◽  
Novel Drug ◽  
Novel Drug Targets

AbstractThe filarial nematodeBrugia malayirepresents a leading cause of disability in the developing world, causing lymphatic filariasis in nearly 40 million people. Currently available drugs are not well-suited to mass drug administration efforts, so new treatments are urgently required. One potential vulnerability is the endosymbiotic bacteriaWolbachia—present in many filariae—which is vital to the worm.Genome scale metabolic networks have been used to study prokaryotes and protists and have proven valuable in identifying therapeutic targets, but only recently have been applied to eukaryotic organisms. Here, we presentiDC625, the first compartmentalized metabolic model of a parasitic worm. We used this model to show how metabolic pathway usage allows the worm to adapt to different environments, and predict a set of 99 reactions essential to the survival ofB. malayi. We validated three of those reactions with drug tests and demonstrated novel antifilarial properties for all three compounds.

Novel drug targets in 2019

2020 ◽  
Vol 19 (5) ◽  
pp. 300-300 ◽  
Author(s):  
Sorin Avram ◽  
Liliana Halip ◽  
Ramona Curpan ◽  
Tudor I. Oprea
Keyword(s):  
Drug Targets ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Identification of Polo-like kinases as potential novel drug targets for influenza A virus

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Marie O. Pohl ◽  
Jessica von Recum-Knepper ◽  
Ariel Rodriguez-Frandsen ◽  
Caroline Lanz ◽  
Emilio Yángüez ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Drug Targets ◽  
Influenza A ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

10.3791/54738 ◽  
2016 ◽  
Author(s):  
Eamonn Morrison ◽  
Patty Wai ◽  
Andri Leonidou ◽  
Philip Bland ◽  
Saira Khalique ◽  
...  
Keyword(s):  
Functional Genomics ◽  
Cancer Cell ◽  
Drug Targets ◽  
Cell Spheroid ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christos Dimitrakopoulos ◽  
Sravanth Kumar Hindupur ◽  
Marco Colombi ◽  
Dritan Liko ◽  
Charlotte K. Y. Ng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Targets ◽  
Mtor Signaling ◽  
Omics Data ◽  
Genetic Changes ◽  
Genetic Aberrations ◽  
Functional Consequences ◽  
Novel Drug ◽  
Novel Drug Targets ◽  
Omics Data Integration

Abstract Background Genetic aberrations in hepatocellular carcinoma (HCC) are well known, but the functional consequences of such aberrations remain poorly understood. Results Here, we explored the effect of defined genetic changes on the transcriptome, proteome and phosphoproteome in twelve tumors from an mTOR-driven hepatocellular carcinoma mouse model. Using Network-based Integration of multi-omiCS data (NetICS), we detected 74 ‘mediators’ that relay via molecular interactions the effects of genetic and miRNA expression changes. The detected mediators account for the effects of oncogenic mTOR signaling on the transcriptome, proteome and phosphoproteome. We confirmed the dysregulation of the mediators YAP1, GRB2, SIRT1, HDAC4 and LIS1 in human HCC. Conclusions This study suggests that targeting pathways such as YAP1 or GRB2 signaling and pathways regulating global histone acetylation could be beneficial in treating HCC with hyperactive mTOR signaling.

Sign in / Sign up

Export Citation Format

Share Document