Biology subjects

Newell, C. L.

Publications and source records attributed to Newell, C. L..

3 recordsLinked to original sources

bioRxiv2025

An intercellular metabolic relay for brain sparingin Drosophila

Brain sparing protects growth of the central nervous system (CNS) at the expense of other developing organs during nutrient restriction. This survival strategy is conserved from Drosophila to mammals but little is known about its underlying metabolic mechanisms. Here, we show that CNS uptake and catabolism of circulating glutamine is essential for neural stem cell proliferation during brain sparing but not normal brain development. Glutamine is imported into perineurial glia of the blood-brain-barrier, which upregulate glutaminase (Gls) and vesicular glutamate transporter 1 (VGlut1) to promote glutaminolysis and glutamate secretion. Neural stem cells then import released glutamate via excitatory amino acid transporter 1 (Eaat1) and maintain it at homeostatic levels via glutamine synthetase 1 (Gs1). Glutamine nitrogen contributes surprisingly little to newly synthesized DNA or protein in neural stem cells but its carbon fuels the oxidative tricarboxylic acid cycle. These findings identify an intercellular metabolic relay specifically required to sustain the proliferation of neural stem cells during brain sparing.

developmental biology↗

bioRxiv2024

Identification of a specialized lipid barrier for Drosophila metamorphosis

In many terrestrial insects, the onset of metamorphosis marks a transition from humid to dry environments. Yet how metamorphosing insect pupae protect themselves against the threat of dehydration remains unclear. Here, we identify the chemical composition and biosynthetic origins of a lipid desiccation barrier specific to the pupal and sexually-immature adult stages of Drosophila melanogaster. This barrier comprises unisex hyper-long hydrocarbons, 29-37 carbons in length, which are synthesized by larval oenocytes and stored in the larval fat body before being deployed on the pupal and young adult cuticles. We show that the fatty acid elongase EloHL is required for the biosynthesis of hyper-long hydrocarbons that are essential for the barrier to water loss during metamorphosis. Across the Drosophila genus, many species express unisex profiles of hyper-long hydrocarbons and, as young adults, transition to sex-specific shorter hydrocarbons with known pheromonal functions. The desert species D. mojavensis, however, retains hyper-long hydrocarbons during adulthood likely as an adaptation to an arid environment. Our study reveals how the cuticular lipid barrier is tuned to meet changing environmental pressures during insect development and evolution.

developmental biology↗

bioRxiv2019

Cryogenic OrbiSIMS Localizes Semi-Volatile Molecules in Biological Tissues

OrbiSIMS is a recently developed instrument for label-free imaging of chemicals with micron spatial resolution and high mass resolution. Here we report a cryogenic workflow for OrbiSIMS (Cryo-OrbiSIMS) that improves chemical detection of lipids and other biomolecules in tissues. Cryo-OrbiSIMS decreases ion-beam induced fragmentation, allowing large molecules such as triglycerides to be more reliably identified. It also increases chemical coverage to include biomolecules with intermediate or high vapor pressures, such as free fatty acids and semi-volatile organic compounds (SVOCs). We find that Cryo-OrbiSIMS reveals the hitherto unknown localization patterns of SVOCs with high spatial and chemical resolution in diverse plant, animal and human tissues. We also show that Cryo-OrbiSIMS can be combined with genetic analysis to identify enzymes regulating SVOC metabolism. Cryo-OrbiSIMS is applicable to high resolution imaging of a wide variety of non-volatile and semi-volatile molecules across many areas of biomedicine.

biochemistry↗