Biology subjects

Gutierrez, M. L.

Publications and source records attributed to Gutierrez, M. L..

3 recordsLinked to original sources

bioRxiv2025

Sorghum Metabolic Atlas: Large-Scale Mapping of Subcellular Enzyme Localization in Sorghum bicolor

Plant metabolism drives traits essential for productivity and resilience, yet understanding metabolic networks requires subcellular, cellular, and tissue-level spatial context that remains limited, particularly in crop species. Experimentally-derived subcellular localization data for enzymes are sparse, constraining analyses of metabolic organization in the cell. We developed a high-throughput protoplast transformation and fluorescent protein (FP) tagging system optimized for Sorghum bicolor, a climate-resilient C4 crop. Using this platform, we experimentally determined the subcellular localization of 234 metabolic enzymes spanning 184 pathways. The sorghum enzymes we characterized localize to 12 subcellular compartments. Comparison with computational predictions highlights variable accuracy across compartments, and cross-species comparison with Arabidopsis thaliana shows partial agreement with available experimental data. All data are accessible through the Sorghum Metabolic Atlas (www.sorghummetabolicatlas.org) web platform, enabling search, visualization, and download. This study presents a large-scale experimental dataset of enzyme localization in sorghum, providing a resource for studies of plant metabolic organization and comparative analyses.

plant biology↗

bioRxiv2025

High-Throughput Screening on Primary Tumor-Associated Microglia and Macrophages Identifies HDAC Inhibitors as Enhancers of Phagocytosis and Potent Partners for Immunotherapy in Glioblastoma

Glioblastoma multiforme (GBM) is a lethal brain tumor with limited treatment options. Tumor-associated macrophages and microglia (TAMs) drive immune suppression and tumor progression, making them a key therapeutic target for GBM. Enhancing TAM phagocytosis in GBM has shown promise, particularly with innate checkpoint inhibitors, such as CD47-blocking antibodies. However, small molecule approaches, which offer tunable and potentially synergistic mechanisms, remain underexplored in this context. In this study, we conducted the first large-scale chemical screen on primary TAMs from patients with GBM, identifying histone deacetylase (HDAC) inhibitors as potent inducers of phagocytosis. These compounds demonstrated phagocytosis-inducing effects across multiple GBM patient samples, with further amplification when combined with CD47 blockade. In a xenograft GBM model, HDAC inhibitors enhanced phagocytosis and suppressed tumor growth, with even greater efficacy in combination with CD47 antibodies. Our findings highlight HDAC inhibitors as promising agents to reprogram TAMs and synergize with immune checkpoint therapies, offering a novel strategy to bolster anti-tumor immunity in GBM.

cancer biology↗

bioRxiv2021

Salty surfaces deter feeding in a blood-sucking disease vector

Salts are essential nutrients required for many physiological processes, and deficient or excessive salt results in adverse health problems. Taste is the ultimate sensory modality involved in resource quality assessment, resulting in acceptance or rejection. Here, we show that detection of high-salt substrates by a salt-sensitive antennal gustatory receptor neuron, S1-GRN, results in feeding avoidance in the hematophagous bug Rhodnius prolixus. Knock-down of two antennal-expressed amiloride-sensitive pickpocket channel receptors (PPKs; RproPPK014276 and RproPPK28) using RNA interference, prevents avoidance of bugs to high-salt substrates. Tracing antennal GRNs to the central nervous system reveals the antennal lobes as a gustatory processing center. The identification of the gustatory basis of high-salt detection in a blood feeder provides novel targets to prevent biting and feeding, as well as to promote substrate avoidance in a relevant disease vector. Significance StatementDetection of aversive gustatory stimuli induces avoidance responses in animals. Avoidance acquires particular interest if it reduces the biting rates of blood-feeding insects of medical relevance. Here we describe the molecular and physiological basis of high-salt detection in the blood-sucking disease vector Rhodnius prolixus. We show that detection of high-salt substrates through two PPK receptors expressed in an antennal gustatory receptor neuron produces feeding avoidance. Understanding these gustatory-driven aversive responses allows the hitherto overlooked use of gustatory molecules as a complement to known olfactory repellents.

physiology↗