Biology subjects

Bailey, S. R.

Publications and source records attributed to Bailey, S. R..

4 recordsLinked to original sources

bioRxiv2020

Temporal changes in metabolism late in seed development affect biomass composition in soybean

The inverse correlation between protein and oil production in soybeans is well-documented; however, it has been based primarily on the composition of mature seeds. Though this is the cumulative result of events over the course of soybean seed development, it does not convey information specific to metabolic fluctuations during developmental growth regimes. Maternal nutrient supply via seed coat exudate measurements and metabolite levels within the cotyledon were assessed across development to identify trends in the accumulation of central carbon and nitrogen metabolic intermediates. Active metabolic operation during late seed development was probed through transient labeling with 13C substrates. The results indicated: i) a drop in lipid during seed maturation with a concomitant increase in carbohydrates, ii) a transition from seed filling to maturation phase characterized by quantitatively balanced changes in the carbon use and CO2 release, iii) changes in measured carbon and nitrogen resources supplied maternally over development, iv) 13C metabolites processed through gluconeogenesis towards sustained carbohydrate accumulation as the maternal nutrient supply diminishes, and v) oligosaccharide biosynthetic metabolism during seed coat senescence at maturation. These results highlight temporal engineering targets for altering final biomass composition to increase the value of soybeans and a path to breaking the inverse seed protein and oil correlation. One-sentence summaryAssessment of temporal changes in metabolism during soybean seed development indicated that lipid turnover during maturation contributes carbon for gluconeogenic production of carbohydrates.

plant biology↗

bioRxiv2020

Shifting carbon flux from non-transient starch to lipid allows oil accumulation in transgenic tobacco leaves

Plant leaf biomass is composed predominantly of carbohydrate and protein with less than 5% dry weight allocated to lipid and less than 1% of total lipid in the form of triacylglycerols (TAGs). The combined overexpression of multiple genes involved in different aspects of TAG synthesis and stabilization can result in TAG accumulation to over 30% dry weight in tobacco leaves, presumably requiring many metabolic adjustments within plant cells. The metabolic consequences to the combined source and sink capacities of high oil accumulating transgenic tobacco leaves compared to wild-type were inspected across development and photoperiod by utilizing foliar biomass components and 13CO2 flux through central carbon intermediates. Lipid biosynthesis was investigated through assessment of acyl-acyl carrier protein (ACP) pools using a recently derived quantification method that was extended to accommodate isotopic labeling. Lipids accumulated stepwise over plant development in the high-oil leaves, with 13CO2-labeling studies confirming increased carbon flux to lipids. The large increase in lipid content was concurrent with a decrease in foliar starch, with limited contribution from non-sucrose soluble sugars, indicating a redirection of carbon from starch to lipids. Starch accumulated non-transiently with plant age in wild-type leaves, suggesting an inherent capacity for a developmentally-regulated carbon sink in tobacco leaves that may have enabled the programmed altered carbon partitioning to lipids in transgenics. These studies provide insight into the metabolic plasticity of dual source-sink leaves over development and may in part explain recent successful leaf lipid engineering efforts in tobacco. One sentence summaryEngineering high oil accumulation in tobacco leaves is enabled by inherent source-sink plasticity associated with non-transient foliar starch accumulation over development.

plant biology↗

bioRxiv2020

Identification of human CD4+ T cell populations with distinct antitumor activity

How naturally arising human CD4+ T helper subsets impact tumor immunity is unknown. We reported that human CD4+CD26high T cells elicit potent immunity against solid tumor malignancies. As CD26high T cells secrete type-17 cytokines and have been categorized as Th17 cells, we posited these helper populations would possess similar molecular properties. Herein, we reveal that CD26high T cells are epigenetically and transcriptionally distinct from Th17 cells. Of clinical significance, CD26high T cells engineered with a chimeric antigen receptor (CAR) ablated large human tumors to a greater extent than enriched Th17, Th1, or Th2 cells. Moreover, CD26high T cells mediated curative responses in mice, even when redirected with a suboptimal CAR and without the aid of CD8+ CAR T cells. CD26high T cells co-secreted effector cytokines at heightened levels and robustly persisted. Collectively, our work reveals the potential of human CD4+ T cell populations to improve durability of solid tumor therapies.

immunology↗

bioRxiv2017

PI3Kδ inhibition supports memory T cells with enhanced antitumor fitness

Phosphatidylinositol-3-kinase p110{delta} (PI3K{delta}) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells (Tregs). Yet, little is known about the direct impact of PI3K{delta} blockade on effector T cells from CAL-101 therapy. Herein, we demonstrate a direct effect of p110{delta} inactivation via CAL-101 on murine and human CD8+ T cells that promotes a strong undifferentiated memory phenotype (elevated CD62L/CCR7, CD127 and Tcf7). These CAL-101 T cells also persisted longer after transfer and exerted stronger antitumor immunity compared to traditionally expanded CD8+ T cells in two solid tumor models. Thus, this report describes a novel direct enhancement of CD8+ T cell memory by a p110{delta} inhibitor that leads to markedly improved tumor regression. This finding has significant implications to improve outcomes from next generation cancer immunotherapies.\n\nHighlightsO_LIIn vitro blockade of PI3K p110{delta} with CAL-101 endows antitumor T cells with a stronger memory phenotype than those treated with AKTi\nC_LIO_LIThe strong memory phenotype of CAL-101 treated cells translates into improved survival of mice bearing aggressive tumors after adoptive transfer of these T cells\nC_LIO_LIHuman CAR engineered T cells treated with CAL-101 possess an enhanced memory phenotype and robust antitumor efficacy\nC_LIO_LIThe antitumor efficacy of CAL-101 primed T cells is not mediated by high CD62L or CD127 expression, but is likely driven by their stem memory phenotype\nC_LI\n\neTOC BlurbBowers et al report a novel function of PI3K blockade using the p110{delta} subunit inhibitor CAL-101 to induce memory and antitumor potency in CD8+ T cells. Ex vivo treatment of T cells with CAL-101 leads to improved antitumor control and subject survival in both murine transgenic T cell and human CAR T cell models.

cancer biology↗