Biology subjects

Schrader, A.

Publications and source records attributed to Schrader, A..

5 recordsLinked to original sources

bioRxiv2025

Thermal proteome profiling identifies mitochondrial aminotransferases involved in cysteine catabolism via persulfides in plants

Cysteine is a central metabolite in plant sulfur metabolism, with key roles in biosynthesis, redox regulation, and stress responses. While a mitochondrial cysteine degradation pathway has been described, the enzyme catalyzing its initial transamination step remained unidentified. Here, we applied thermal proteome profiling (TPP) to Arabidopsis mitochondria to uncover cysteine-interacting proteins. TPP successfully detected known cysteine-utilizing enzymes, validating its utility in plant metabolic research. Among newly identified targets were two aminotransferases annotated as alanine and aspartate aminotransferases that catalyze the transamination of cysteine to 3-mercaptopyruvate in vitro. These enzymes, together with the sulfurtransferase STR1 and the persulfide dioxygenase ETHE1, reconstituted a complete mitochondrial cysteine catabolic pathway. Kinetic data indicate that alanine aminotransferase, in particular, may function in vivo under physiological cysteine levels. Additionally, GABA aminotransferase was inhibited by cysteine, suggesting a regulatory role in stress metabolism. Beyond enzyme identification, the dataset provides a resource for exploring cysteine-mediated regulation of transporters, RNA-editing factors, and respiratory components. Given cysteines emerging role as a metabolic signal in stress responses, and the importance of allosteric regulation in amino acid metabolism, these findings highlight the broader regulatory potential of cysteine-protein interactions in plants. This study demonstrates the utility of TPP for elucidating metabolite-protein networks and advancing our understanding of plant mitochondrial metabolism.

plant biology↗

bioRxiv2024

SpaceExpress: a method for comparative spatial transcriptomics based on intrinsic coordinate systems of tissues

Spatial transcriptomics (ST) technologies have enabled new explorations into the spatial organization of tissues and their functional implications. However, one of the most fundamental analyses - comparative analysis of spatial gene expression across phenotypes - remains a formidable challenge. We introduce SpaceExpress, a novel statistical tool for detecting phenotype-associated changes in spatial expression patterns. SpaceExpress employs a neural network to embed multiple ST samples in a common latent space, enabling robust cross-sample comparisons despite structural and technical variations. It then uses spline regression to test differential spatial expression of genes between conditions, identifying specific regions of the tissue where expression patterns diverge and quantifying the magnitude of those differences, with rigorous false discovery control and handling of multiple replicates per condition. It includes visualization tools to help interpret spatial pattern differences. We demonstrate the tools effectiveness on synthetic and real ST datasets, revealing mechanistic insights into behavior- and development-related neurogenomic changes in honey bees and mice. Our work extends the highly influential paradigm of differential gene expression analysis to spatial omics.

bioinformatics↗

bioRxiv2024

Cisplatin drives mitochondrial dysregulation in sensory hair cells

Cisplatin is a chemotherapy drug that causes permanent hearing loss by injuring cochlear hair cells. The mechanisms that initiate injury are not fully understood, but mitochondria have emerged as potential mediators of hair cell cytotoxicity. Using in vivo live imaging of hair cells in the zebrafish lateral-line organ expressing a genetically encoded indicator of cumulative mitochondrial activity, we first demonstrate that greater redox history increases susceptibility to cisplatin. Next, we conducted time-lapse imaging to understand dynamic changes in mitochondrial homeostasis and observe elevated mitochondrial and cytosolic calcium that surge prior to hair cell death. Furthermore, using a localized probe that fluoresces in the presence of cisplatin, we show that cisplatin directly accumulates in hair cell mitochondria, and this accumulation occurs before mitochondrial dysregulation and apoptosis. Our findings provide evidence that cisplatin directly targets hair cell mitochondria and support that the mitochondria are integral to cisplatin cytotoxicity in hair cells.

neuroscience↗

bioRxiv2022

Local adaptation of life-history traits within urban populations of Arabidopsis thaliana

O_LIThe challenges to which plants are exposed in urban environments represent, in miniature, the challenges plants face as a result of global environmental change. Hence, urban habitats provide a unique opportunity to assess whether processes of local adaptation are taking place despite the short temporal and geographical scales that characterize the Anthropocene. C_LIO_LIWe quantified the ecological diversity of urban habitats hosting A. thaliana populations. Using plant community indicators, we show that these patches differ in their levels of soil nutrient content and disturbance. Accordingly, plants in each patch displayed a range of flowering time, size and fitness. C_LIO_LIUsing a deep sampling approach coupled with reduced genome-sequencing, we demonstrate that most individuals can be assigned to a limited set of clonal lineages; the genetic diversity of these lineages is a sample of the diversity observed in western European populations of the species, indicating that established urban populations originate from a broad regional pool of lineages. C_LIO_LIWe assessed the genetic and phenotypic diversity of these lineages in a set of common garden experiments. We report marked genetic differences in life-history traits, including time of primary and secondary dormancy as well as of flowering. These genetic differences in life-history traits are not randomly distributed but sorted out by ecological differences among sites of origin. C_LIO_LISynthesis: Our study shows that the genetically diverse phenology of a regional A. thaliana gene pool is not randomly distributed but filtered by heterogeneity in the urban environment. To out knowledge, this report is the first to show a pattern indicative of environmental filtering enhancing local genetic adaptation within urban environments. We conclude that environmental filtering helps maintain functional diversity within species. C_LI

evolutionary biology↗

bioRxiv2020

Macrophages respond rapidly to ototoxic injury of lateral line hair cells but are not required for hair cell regeneration

The sensory organs of the inner ear contain resident populations of macrophages, which are recruited to sites of cellular injury. Such macrophages are known to phagocytose the debris of dying cells but the full role of macrophages in otic pathology is not understood. Lateral line neuromasts of zebrafish contain hair cells similar to those in the inner ear, and the optical clarity of larval zebrafish permits direct imaging of cellular interactions. In this study, we used larval zebrafish to characterize the response of macrophages to ototoxic injury of lateral line hair cells. Macrophages migrated into neuromasts within 20 min of exposure to the ototoxic antibiotic neomycin. The number of macrophages in close proximity of injured neuromasts was similar to that observed near uninjured neuromasts, suggesting that this early inflammatory response was mediated by local macrophages. Upon entering injured neuromasts, macrophages actively phagocytosed hair cell debris. Such phagocytosis was significantly reduced by inhibiting Src-family kinases. Using chemical-genetic ablation of macrophages prior to ototoxic injury, we also examined whether macrophages were essential for the initiation of hair cell regeneration after neomycin exposure. Results revealed only minor differences in hair cell recovery in macrophage-depleted vs. control fish, suggesting that macrophages are not essential for the regeneration of lateral line hair cells.

neuroscience↗