Journal article
Identifying potential dietary treatments for inherited metabolic disorders using Drosophila nutrigenomics
Felipe Martelli, Jiayi Lin, Sarah Mele, Wendy Imlach, Oguz Kanca, Christopher K Barlow, Jefferson Paril, Ralf B Schittenhelm, John Christodoulou, Hugo J Bellen, Matthew DW Piper, Travis K Johnson
Cell Reports | Elsevier | Published : 2024
Open access
Abstract
Inherited metabolic disorders are a group of genetic conditions that can cause severe neurological impairment and child mortality. Uniquely, these disorders respond to dietary treatment; however, this option remains largely unexplored because of low disorder prevalence and the lack of a suitable paradigm for testing diets. Here, we screened 35 Drosophila amino acid disorder models for disease-diet interactions and found 26 with diet-altered development and/or survival. Using a targeted multi-nutrient array, we examine the interaction in a model of isolated sulfite oxidase deficiency, an infant-lethal disorder. We show that dietary cysteine depletion normalizes their metabolic profile and res..
View full abstractGrants
Awarded by National Health and Medical Research Council
Awarded by National Institutes of Health
Awarded by NIH/ORIP
Funding Acknowledgements
We thank the Bloomington Drosophila Stock Center and Christian Klambt for fly stocks, Oliver Anderson and Harshini Thiyagarajah for technical assistance, and the Australian Drosophila Biomedical Research Facility (Ozdros) for stock importation, as well as Christen Mirth, Richard Burke, and members of the Johnson and Piper labs for helpful discussions. This work is supported by a National Health and Medical Research Council Ideas grant (APP1182330) to M.D.W.P. and T.K.J. and a National Institutes of Health grant (5U01HG007530-08) to T.K.J. J.L. and S.M. are supported by Australian Government Research Training Program Scholarships. This study used BPA-enabled (Bioplatforms Australia) /NCRIS (National Collaborative Research Infrastructure Strategy)-enabled infrastructure located at the Monash Proteomics and Metabolomics Facility. The research conducted at the Murdoch Children's Research Institute (MCRI) was supported by the Victorian Government's Operational Infrastructure Support Program. The Chair in Genomic Medicine awarded to J.C. is generously supported by The Royal Children's Hospital Foundation. H.J.B. and O.K. are supported by R24 OD031447 from NIH/ORIP. T.K.J. is supported by an Australian Research Council Future Fellowship.