Biology subjects

Hernandez, J. S.

Publications and source records attributed to Hernandez, J. S..

4 recordsLinked to original sources

bioRxiv2026

Durable protection against SIV challenge by adeno-associated virus delivery of Env-specific antibodies

Conventional vaccines have so far failed to elicit the types of antibodies needed for protection against HIV. As an alternative, we evaluated adeno-associated virus (AAV) delivery of rhesus macaque antibodies to the SIV envelope glycoprotein for protection against SIV challenge. AAV vectors encoding a broadly neutralizing antibody (bnAb) and an antibody that only mediates antibody-dependent cellular cytotoxicity (ADCC) were administered individually or together to separate groups of rhesus macaques. Antibody expression was sustained for more than a year with minimal anti-drug antibody responses. All animals that received a control antibody or the ADCC-only antibody became infected after five low-dose, intrarectal challenges with SIVmac239. In contrast, 14 of 16 animals that received the bnAb resisted two rounds of twelve SIVmac239 challenges more than a year apart. Thus, AAV delivery of a single bnAb can afford durable protection against a pathogenic SIV strain that is notoriously difficult to protect against by vaccination.

immunology↗

bioRxiv2024

Regulation of plant metabolism under elevated CO2

Plant responses to changing environments afford complex regulation at transcriptome and proteome level to maintain metabolic homeostasis. Homeostasis itself constitutes a complex and dynamic equilibrium of metabolic reactions and transport processes among cellular compartments. In the present study, we aimed at the highest possible resolution of this network by combining analysis of transcriptome, proteome and subcellular resolved metabolome of plants exposed to rising carbon dioxide concentrations over a time course of one week. To prove suitability of our approach, we included mutants affected in photorespiratory metabolism and, thus, should deviate from the wildtype in their response to elevated CO2. Our multi-omics analysis revealed that the hpr1-1 mutant, defective in peroxisomal hydroxypyruvate reduction, is also affected in cytosolic pyruvate metabolism, reaching out to cysteine synthesis, while the hexokinase mutant hxk1 displays a disturbed redox balance upon changing CO2 levels. For the third mutant, defective in the mitochondrial protein BOU, we found compelling evidence that the function of this transporter is related to lipoic acid metabolism, thus challenging current interpretations. This demonstrates that the combined omics approach introduced here opens new insights into complex metabolic interaction of pathways shared among different cellular compartments.

plant biology↗

bioRxiv2023

Temperature acclimation of photosynthesis and carbohydrate metabolism are related to the geographical origin of Arabidopsis thaliana

Acclimation is a multigenic trait by which plants adjust photosynthesis and metabolism to cope with a changing environment. Here, natural variation of photosynthetic and metabolic acclimation was analyzed in response to low and elevated temperature. For this, 18 natural accessions of Arabidopsis thaliana, originating from Africa and Europe, were grown at 22{degrees}C before being exposed to 4{degrees}C and 34{degrees}C for cold and heat acclimation, respectively. Amounts of carbohydrates were quantified together with their subcellular distribution across plastids, cytosol and vacuole. Linear electron transport rates (ETRs) were determined together with maximum quantum efficiency of photosystem II (Fv/Fm) for all growth conditions and under temperature fluctuation. Under elevated temperature, residuals of ETR under increasing photosynthetic photon flux densities were found to significantly correlate with the longitudinal gradient of the geographic origin of accessions indicating a naturally occurring east-west gradient of photosynthetic acclimation capacities. Further, in heat acclimated plants, vacuolar fructose amount was found to positively correlate with longitude while plastidial and cytosolic amounts were found to be negatively correlated. Plastidial sucrose concentrations were found to positively correlate with maximal ETRs under fluctuating temperature indicating a stabilizing role within the chloroplast. In summary, our findings revealed specific subcellular carbohydrate distributions which contribute differentially to photosynthetic efficiencies of natural Arabidopsis thaliana accessions across a longitudinal gradient. This sheds light on the relevance of subcellular metabolic regulation for photosynthetic performance in a fluctuating environment and supports the physiological interpretation of naturally occurring genetic variation of temperature tolerance and acclimation.

plant biology↗

bioRxiv2022

The trade-off function of photorespiration in a changing environment

The photorespiratory pathway in plants comprises metabolic reactions distributed across several cellular compartments. It emerges from the dual catalytic function of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) which either carboxylates or oxygenates ribulose-1,5-bisphosphate (RuBP). Carboxylation reactions produce 3-phospho-glycerate (3PGA) molecules which are substrate for central carbohydrate metabolism while oxygenation forms 2-phosphoglycolate (2PG) molecules which are substrate for the multicompartmental recovery process of photorespiration. Further, 2PG is a strong inhibitor of several enzymes involved in the Calvin-Benson-Bassham cycle which challenges the experimental and theoretical study of carbon assimilation, photorespiration and metabolic regulation in vivo. Here, an approach of structural kinetic modeling (SKM) is presented to investigate the extend of stabilization of CBC and carbohydrate metabolism by photorespiration. Further, our approach highlights the importance of feedback regulation by 2-PG for alleviation of environmental perturbation. Our findings indicate that oxygenation of RuBP by Rubisco significantly stabilizes CBC activity and, thus, carbohydrate metabolism. Based on our findings, we suggest a trade-off function of photorespiration which reduces carbon assimilation rates but simultaneously stabilizes metabolism by increasing plasticity of metabolic regulation within the chloroplast. Furthermore, our analysis suggests a stabilizing effect of increasing the partition of newly assimilated carbon going towards sucrose biosynthesis. With this, our analysis sheds light on the role of a multicompartmental metabolic pathway in stabilizing plant metabolism within a changing environment.

plant biology↗