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Animal Models

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Identifying Potential Dietary Treatments for Inherited Metabolic Disorders Using Drosophila Nutrigenomics

Martelli et al., Cell Reports. 2024.

https://www.sciencedirect.com/science/article/pii/S221112472400189X?via%3Dihub=

Inherited metabolic disorders are known to cause severe neurological impairment and child mortality and can sometimes respond to dietary treatment; however, a suitable paradigm for testing diets is lacking for developing effective dietary treatment. In this study, researchers found that 26 of 35 Drosophila amino acid disorder models screened for disease–diet interactions displayed diet-altered development and/or survival. Among these models, researchers showed that dietary cysteine depletion normalizes metabolic profile and rescues development, neurophysiology, behavior, and life span in a model for isolated sulfite oxidase deficiency. These findings demonstrate the value of using Drosophila in studying diet-sensitive metabolic disorders and developing potential dietary therapies. Supported by ORIP (R24OD031447) and NHGRI.

Newly Identified Roles for PIEZO1 Mechanosensor in Controlling Normal Megakaryocyte Development and in Primary Myelofibrosis

Abbonante et al., American Journal of Hematology. 2024.

https://pubmed.ncbi.nlm.nih.gov/38165047/

Mechanisms through which mature megakaryocytes (Mks) and their progenitors sense the bone marrow extracellular matrix to promote lineage differentiation are only partially understood. The authors report that PIEZO1, a mechanosensitive cation channel, is expressed in mouse and human Mks, and activation of PIEZO1 increased the number of immature Mks in mice. Piezo1/2 knockout mice show an increase in Mk size and platelet count, both at basal state and upon marrow regeneration. Together, these data suggest that PIEZO1 places a brake on Mk maturation and platelet formation in physiology, and its upregulation might contribute to aggravating disease. Supported by ORIP (K01OD025290), NHGRI, NHLBI, and NCATS.

Multiplexed Drug-Based Selection and Counterselection Genetic Manipulations in Drosophila

Matinyan et al., Cell Reports. 2021.

https://www.cell.com/cell-reports/pdf/S2211-1247(21)01147-5.pdf

Many highly efficient methods exist which enable transgenic flies to contribute to diagnostics and therapeutics for human diseases. In this study, researchers describe a drug-based genetic platform with four selection and two counterselection markers, increasing transgenic efficiency by more than 10-fold compared to established methods in flies. Researchers also developed a plasmid library to adapt this technology to other model organisms. This highly efficient transgenic approach significantly increases the power of not only Drosophila melanogaster but many other model organisms for biomedical research. Supported by ORIP (P40OD018537, P40OD010949, R21OD022981), NCI, NHGRI, NIGMS, and NIMH.