Summary of Study ST004268
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 PR002694. The data can be accessed directly via it's Project DOI: 10.21228/M8F26W 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 | ST004268 |
| Study Title | Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration - Drosophila |
| Study Summary | In the brain, tryptophan byproducts are involved in the biosynthesis of proteins, energy-rich molecules (e.g., NAD+), and neurotransmitters (serotonin and melatonin). Impaired tryptophan catabolism, seen in aging, neurodegeneration and psychiatric diseases affects mood, learning, and sleep; however, the reasons for those impairments in elder and these ailments remain unknown. Our results from Drosophila melanogaster models show how the SIRT6-regulated accumulation of neurotoxic metabolites from the kynurenic pathway, at the expense of serotonin and melatonin, can affect various processes in the brain, leading to behavioral defects. However, by redirecting tryptophan through TDO2 inhibition in our new SIRT6-KO D. melanogaster model, the impairments in neuromotor behavior and vacuolar formation - parameters of neurodegeneration - could be significantly reversed. |
| Institute | VIB-KU Leuven Center for Cancer Biology |
| Last Name | Fernández-García |
| First Name | Juan |
| Address | Campus Gasthuisberg, O&N4, Herestraat 49, box 912, 3000 Leuven, Belgium |
| juan.fernandezgarcia@kuleuven.be | |
| Phone | +32 16 37 32 61 |
| Submit Date | 2025-10-03 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML, d |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-10-30 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002694 |
| Project DOI: | doi: 10.21228/M8F26W |
| Project Title: | Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration |
| Project Summary: | In the brain, tryptophan byproducts are involved in the biosynthesis of proteins, energy-rich molecules (e.g., NAD+), and neurotransmitters (serotonin and melatonin). Impaired tryptophan catabolism, seen in aging, neurodegeneration and psychiatric diseases affects mood, learning, and sleep; however, the reasons for those impairments in elder and these ailments remain unknown. Our results from cellular, Drosophila melanogaster, and mouse models indicate that SIRT6 regulates tryptophan catabolism by balancing its usage. Mechanistically, SIRT6 regulates tryptophan and sleep quality through changes in gene expression of key genes (e.g., TDO2, AANAT), which results in elevated concentration of neurotoxic metabolites from the kynurenic pathway at the expense of serotonin and melatonin production. Such neurotoxic metabolites can affect various processes in the brain. However, by redirecting tryptophan through TDO2 inhibition in our new SIRT6-KO D. melanogaster model, the impairments in neuromotor behavior and vacuolar formation - parameters of neurodegeneration - could be significantly reversed. |
| Institute: | VIB-KU Leuven Center for Cancer Biology |
| Last Name: | Fernández-García |
| First Name: | Juan |
| Address: | Campus Gasthuisberg, O&N4, Herestraat 49, box 912, 3000 Leuven, Belgium |
| Email: | juan.fernandezgarcia@kuleuven.be |
| Phone: | +32 16 37 32 61 |
Subject:
| Subject ID: | SU004421 |
| Subject Type: | Insect |
| Subject Species: | Drosophila melanogaster |
| Taxonomy ID: | 7227 |
| Gender: | Male and female |
Factors:
Subject type: Insect; Subject species: Drosophila melanogaster (Factor headings shown in green)
| mb_sample_id | local_sample_id | Sample source | Genotype | Sex | Batch |
|---|---|---|---|---|---|
| SA497670 | SKO-F2 | D. melanogaster whole animal | SIRT6 KO | Female | 1 |
| SA497671 | SKO-F1 | D. melanogaster whole animal | SIRT6 KO | Female | 1 |
| SA497672 | SKO-F3 | D. melanogaster whole animal | SIRT6 KO | Female | 1 |
| SA497673 | SKO-F4 | D. melanogaster whole animal | SIRT6 KO | Female | 2 |
| SA497674 | SKO-F6 | D. melanogaster whole animal | SIRT6 KO | Female | 2 |
| SA497675 | SKO-F5 | D. melanogaster whole animal | SIRT6 KO | Female | 2 |
| SA497676 | SKO-M1 | D. melanogaster whole animal | SIRT6 KO | Male | 1 |
| SA497677 | SKO-M2 | D. melanogaster whole animal | SIRT6 KO | Male | 1 |
| SA497678 | SKO-M3 | D. melanogaster whole animal | SIRT6 KO | Male | 1 |
| SA497679 | SKO-M4 | D. melanogaster whole animal | SIRT6 KO | Male | 2 |
| SA497680 | SKO-M5 | D. melanogaster whole animal | SIRT6 KO | Male | 2 |
| SA497681 | SKO-M6 | D. melanogaster whole animal | SIRT6 KO | Male | 2 |
| SA497682 | WT-F3 | D. melanogaster whole animal | Wild type | Female | 1 |
| SA497683 | WT-F2 | D. melanogaster whole animal | Wild type | Female | 1 |
| SA497684 | WT-F1 | D. melanogaster whole animal | Wild type | Female | 1 |
| SA497685 | WT-F4 | D. melanogaster whole animal | Wild type | Female | 2 |
| SA497686 | WT-F6 | D. melanogaster whole animal | Wild type | Female | 2 |
| SA497687 | WT-F5 | D. melanogaster whole animal | Wild type | Female | 2 |
| SA497688 | WT-M1 | D. melanogaster whole animal | Wild type | Male | 1 |
| SA497689 | WT-M2 | D. melanogaster whole animal | Wild type | Male | 1 |
| SA497690 | WT-M3 | D. melanogaster whole animal | Wild type | Male | 1 |
| SA497691 | WT-M4 | D. melanogaster whole animal | Wild type | Male | 2 |
| SA497692 | WT-M5 | D. melanogaster whole animal | Wild type | Male | 2 |
| SA497693 | WT-M6 | D. melanogaster whole animal | Wild type | Male | 2 |
| SA497694 | Mock03 | Mock | NA | NA | 1 |
| SA497695 | Mock04 | Mock | NA | NA | 1 |
| SA497696 | Mock05 | Mock | NA | NA | 2 |
| SA497697 | Mock06 | Mock | NA | NA | 2 |
| Showing results 1 to 28 of 28 |
Collection:
| Collection ID: | CO004414 |
| Collection Summary: | Wild type D. melanogaster flies, strain w1118, were kindly donated by Dr David Ben-Menahem (Ben-Gurion University, Israel). All flies used in the study were backcrossed to w1118 for 8 generations. SIRT6 (#39) D. melanogaster mutant strain was a kind gift from Dr Alena Bruce Krejci from the University of South Bohemia in the Czech Republic. Flies were maintained under non-crowding conditions on standard cornmeal diet 5g dextrose, 2.5% yeast extract, 8.6% cornmeal, 2% agar, 0.1% ortho-phosphoric acid, and 0.1% propionic acid) and grown at 25oC with 12h light/dark cycle. Age-matched flies were used for all experiments. |
| Sample Type: | Whole animals |
Treatment:
| Treatment ID: | TR004430 |
| Treatment Summary: | The SIRT6 knockout flies were created by crossing transgenic Sirt6 gRNA flies with UAS-Cas9 stock, selecting the Sirt6-deficient allele and back-crossing the stock five times to the w1118 background. The resulting homozygous stock contained Sirt6 alleles with four nucleotide deletions at position 96-99 after ORF, causing a translational shift after the first 31 amino acids of Sirt6. |
Sample Preparation:
| Sampleprep ID: | SP004427 |
| Sampleprep Summary: | Drosophila melanogaster metabolite extraction was performed in a mixture of ice/dry ice, by a cold two-phase methanol–water–chloroform solution. The samples were resuspended in 800 μl of precooled methanol/water (5:3 v/v). Afterwards, 500 μl of precooled chloroform was added to each sample. Samples were vortexed for 10 min at 4 °C and then centrifuged (max. speed, 10 min, 4 °C). The methanol–water phase containing polar metabolites was separated and dried using a vacuum concentrator at 4 °C overnight, and then stored at -80 °C until sample preparation for LC-MS analysis. Polar metabolite extracts previously stored at -80 °C were resuspended in 50 µL of water prior to LC-MS analysis. |
| Processing Storage Conditions: | Described in summary |
| Extract Storage: | Described in summary |
Chromatography:
| Chromatography ID: | CH005397 |
| Chromatography Summary: | For the detection of tryptophan derivatives by LC–MS, we used an Infinity II 1290 liquid chromatography system (Agilent Technologies) with a thermal autosampler set at 4 °C, coupled to a Q-TOF 6546 mass spectrometer (Agilent Technologies). Samples were resuspended in 50 µL of water, and 20 µL of each sample were injected onto a C18 column (Acquity UPLC Premier HSS C18 1.8 μm 2.1 × 100 mm). Metabolite separation was achieved with a flow rate of 0.25 ml/min at 30 °C, and based on the following 40-minute gradient (solvent A = H2O, 0.1% Formic acid, 15 mM acetic acid; solvent B = Acetonitrile + 0.1% Formic acid): 0 min 8% B; 2 min 8% B; 14 min 90% B; 16 min 90% B; 17 min 8% B; 22 min 8% B. |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um) |
| Column Temperature: | 30 °C |
| Flow Gradient: | 0 min 8% B; 2 min 8% B; 14 min 90% B; 16 min 90% B; 17 min 8% B; 22 min 8% B |
| Flow Rate: | 0.25 ml/min |
| Solvent A: | 100% water; 0.1% formic acid; 15 mM acetic acid |
| Solvent B: | 100% acetonitrile; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN007104 |
| Analysis Type: | MS |
| Chromatography ID: | CH005397 |
| Num Factors: | 10 |
| Num Metabolites: | 8 |
| Units: | Peak Area |
