Summary of Study ST001258
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000844. The data can be accessed directly via it's Project DOI: 10.21228/M8KQ4X This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST001258 |
Study Title | Modeling the metabolic interplay between a parasitic worm and its bacterial endosymbiont allows the identification of novel drug targets |
Study Summary | 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 only recently have been applied to eukaryotic organisms. 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 99 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. |
Institute | The Hospital for Sick Children; NYU Langone Health |
Department | |
Last Name | Jones |
First Name | Drew |
Address | 430 E29th Street, WT635A |
drew.jones@nyulangone.org | |
Phone | 6465012054 |
Submit Date | 2019-09-23 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2019-10-11 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
Project ID: | PR000844 |
Project DOI: | doi: 10.21228/M8KQ4X |
Project Title: | Modeling the metabolic interplay between a parasitic worm and its bacterial endosymbiont allows the identification of novel drug targets |
Project Summary: | 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 only recently have been applied to eukaryotic organisms. 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 99 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. |
Institute: | NYU Langone Health |
Last Name: | Jones |
First Name: | Drew |
Address: | 430 E29th Street, WT635A |
Email: | drew.jones@nyulangone.org |
Phone: | 6465012054 |
Subject:
Subject ID: | SU001326 |
Subject Type: | Invertebrate |
Subject Species: | Brugia malayi |
Taxonomy ID: | 6279 |
Species Group: | Invertebrates |
Factors:
Subject type: Invertebrate; Subject species: Brugia malayi (Factor headings shown in green)
mb_sample_id | local_sample_id | Group |
---|---|---|
SA091398 | 1 20AF | AF |
SA091399 | 3 20AF | AF |
SA091400 | 2 20AF | AF |
SA091401 | 6 40AM | AM |
SA091402 | 5 40AM | AM |
SA091403 | 4 40AM | AM |
SA091404 | Blank_2 | Blank |
SA091405 | Blank_3 | Blank |
SA091406 | Blank_1 | Blank |
SA091407 | Blank_5 | Blank |
SA091408 | Blank_4 | Blank |
SA091409 | 10 200 L3 | L3 |
SA091410 | 11 200 L3 | L3 |
SA091411 | 12 200 L3 | L3 |
SA091412 | 9 2e6 Mf | Mf |
SA091413 | 7 2e6 Mf | Mf |
SA091414 | 8 2e6 Mf | Mf |
Showing results 1 to 17 of 17 |
Collection:
Collection ID: | CO001320 |
Collection Summary: | All parasites were obtained from FR3 (Filariasis Research Reagent Resource Center; BEI Resources, Manassas, VA, USA) where they were isolated and separated by sex from infected gerbils (Meriones unguiculatus) or mosquitoes (Aedes aegypti). Worms were flash-frozen and shipped to the New York Blood Center for processing. Stages used for metabolomics analysis included L3 larvae from mosquitoes, adult male and female worms at 120dpi, and microfilaria. The number of worms per sample were 20 adult female worms, 40 adult males, 2X106 microfilariae, and 200 L3 larvae per biological replicate. Samples were washed in 1x PBS and run in triplicate. Adult male and female worms were picked individually from PBS and each biological was weighed. The microfilaria and L3 samples were spun down, the PBS pipetted off, and weighed directly into a metabolomics 2mL screw cap vial with total amounts ranging from 1.3 mg (adult males) to 15.8 mg (microfilaria). Metabolites were extracted and the data analyzed as described in the Supplementary Information. |
Sample Type: | Worms |
Treatment:
Treatment ID: | TR001341 |
Treatment Summary: | All parasites were obtained from FR3 (Filariasis Research Reagent Resource Center; BEI Resources, Manassas, VA, USA) where they were isolated and separated by sex from infected gerbils (Meriones unguiculatus) or mosquitoes (Aedes aegypti). Worms were flash-frozen and shipped to the New York Blood Center for processing. Stages used for metabolomics analysis included L3 larvae from mosquitoes, adult male and female worms at 120dpi, and microfilaria. The number of worms per sample were 20 adult female worms, 40 adult males, 2X106 microfilariae, and 200 L3 larvae per biological replicate. Samples were washed in 1x PBS and run in triplicate. Adult male and female worms were picked individually from PBS and each biological was weighed. The microfilaria and L3 samples were spun down, the PBS pipetted off, and weighed directly into a metabolomics 2mL screw cap vial with total amounts ranging from 1.3 mg (adult males) to 15.8 mg (microfilaria). Metabolites were extracted and the data analyzed as described in the Supplementary Information. |
Sample Preparation:
Sampleprep ID: | SP001334 |
Sampleprep Summary: | Metabolite extraction – The mass of the weighed worm samples was used to scale the metabolite extraction to a ratio of 16.5 mg / 1 mL extraction solvent. Freezing 80% acetonitrile was added directly to each vial containing the samples, along with zirconium disruption beads (0.5 mm, RPI) and homogenized for 3 min at 4°C in a BeadBlasterTM with a 30 sec on, 30 sec off pattern. The resulting lysate was centrifuged at 21,000 x g for 3 min, and 90% of the supernatant volume was transferred to a 1.5 mL microfuge tube for speed vacuum concentration, no heating. The dry extracts were resolublized in a volume of LCMS grade water 1/10th of that used for the homogenization step, sonicated in a water bath for 3 min, and transferred to a glass insert for analysis. |
Combined analysis:
Analysis ID | AN002087 | AN002088 |
---|---|---|
Analysis type | MS | MS |
Chromatography type | HILIC | Reversed phase |
Chromatography system | Thermo Dionex Ultimate 3000 RS | Thermo Dionex Ultimate 3000 RS |
Column | SeQuant ZIC-pHILIC (150 x 2.1mm,5um) | Waters Acquity BEH Phenyl (150 x 2.1mm,1.7um) |
MS Type | ESI | ESI |
MS instrument type | Orbitrap | Orbitrap |
MS instrument name | Thermo Q Exactive HF hybrid Orbitrap | Thermo Q Exactive HF hybrid Orbitrap |
Ion Mode | UNSPECIFIED | UNSPECIFIED |
Units |
Chromatography:
Chromatography ID: | CH001524 |
Instrument Name: | Thermo Dionex Ultimate 3000 RS |
Column Name: | SeQuant ZIC-pHILIC (150 x 2.1mm,5um) |
Chromatography Type: | HILIC |
Chromatography ID: | CH001525 |
Instrument Name: | Thermo Dionex Ultimate 3000 RS |
Column Name: | Waters Acquity BEH Phenyl (150 x 2.1mm,1.7um) |
Chromatography Type: | Reversed phase |
MS:
MS ID: | MS001938 |
Analysis ID: | AN002087 |
Instrument Name: | Thermo Q Exactive HF hybrid Orbitrap |
Instrument Type: | Orbitrap |
MS Type: | ESI |
MS Comments: | Positive/Negative Polarity Switching |
Ion Mode: | UNSPECIFIED |
MS ID: | MS001939 |
Analysis ID: | AN002088 |
Instrument Name: | Thermo Q Exactive HF hybrid Orbitrap |
Instrument Type: | Orbitrap |
MS Type: | ESI |
MS Comments: | Positive/Negative Polarity Switching |
Ion Mode: | UNSPECIFIED |