Biology subjects

Suciu, R.

Publications and source records attributed to Suciu, R..

4 recordsLinked to original sources

bioRxiv2025

Cysteine reactivity profiling identifies host regulators of Mycobacterium tuberculosis replication in human macrophages

Innate immune cells such as monocytes and macrophages provide the earliest defense against infection by intracellular pathogens by initiating signaling pathways and restricting pathogen replication. However, the full complement of proteins that mediate cell-autonomous immunity remains incompletely defined. Here, we applied cysteine-directed activity-based protein profiling (ABPP) to map proteome-wide cysteine reactivity changes in THP-1 monocytes and primary human monocyte-derived macrophages during Mycobacterium tuberculosis (Mtb) infection. Across both cell types, we quantified 148 cysteine residues with altered reactivity. Genetic perturbation of a subset of proteins harboring these changes significantly impacted Mtb replication, revealing functional links between site-specific cysteine reactivity and antimicrobial defense. These data define previously unrecognized host protein changes during Mtb infection and provide a resource for investigating post-translational events that regulate innate immune responses to intracellular bacteria.

immunology↗

bioRxiv2020

A 180 My-old female-specific genome region in sturgeon reveals the oldest known vertebrate sex determining system with undifferentiated sex chromosomes

Several hypotheses explain the prevalence of undifferentiated sex chromosomes in poikilothermic vertebrates. Turnovers change the master sex determination gene, the sex chromosome or the sex determination system (e.g. XY to WZ). Jumping master genes stay main triggers but translocate to other chromosomes. Occasional recombination (e.g. in sex-reversed females) prevents sex chromosome degeneration. Recent research has uncovered conserved heteromorphic or even homomorphic sex chromosomes in several clades of non-avian and non-mammalian vertebrates. Sex determination in sturgeons (Acipenseridae) has been a long-standing basic biological question, linked to economical demands by the caviar-producing aquaculture. Here, we report the discovery of a sex-specific sequence from sterlet (Acipenser ruthenus). Using chromosome-scale assemblies and pool-sequencing, we first identified a ~16 kb female-specific region. We developed a PCR-genotyping test, yielding female-specific products in six species, spanning the entire phylogeny with the most divergent extant lineages (A. sturio, A. oxyrinchus vs. A. ruthenus, Huso huso), stemming from an ancient tetraploidization. Similar results were obtained in two octoploid species (A. gueldenstaedtii, A. baerii). Conservation of a female-specific sequence for a long period, representing 180 My of sturgeon evolution, and across at least one polyploidization event, raises many interesting biological questions. We discuss a conserved undifferentiated sex chromosome system with a ZZ/ZW-mode of sex determination and potential alternatives.

evolutionary biology↗

bioRxiv2019

An activity-guided map of electrophile-cysteine interactions in primary human immune cells

Electrophilic compounds originating from nature or chemical synthesis have profound effects on immune cells. These compounds are thought to act by cysteine modification to alter the functions of immune-relevant proteins; however, our understanding of electrophile-sensitive cysteines in the human immune proteome remains limited. Here, we present a global map of cysteines in primary human T cells that are susceptible to covalent modification by electrophilic small molecules. More than 3000 covalently liganded cysteines were found on functionally and structurally diverse proteins, including many that play fundamental roles in immunology. We further show that electrophilic compounds can impair T cell activation by distinct mechanisms involving direct functional perturbation and/or ligand-induced degradation of proteins. Our findings reveal a rich content of ligandable cysteines in human T cells, underscoring the potential of electrophilic small molecules as a fertile source for chemical probes and ultimately therapeutics that modulate immunological processes and their associated disorders.

immunology↗

bioRxiv2019

Single-cell profiling and SCOPE-seq reveal the lineage dynamics of adult neurogenesis and NOTUM as a key V-SVZ regulator

Neural stem cells (NSCs) and their progeny reside in specialized niches in the adult mammalian brain where they generate new neurons and glia throughout life. Adult NSCs of the ventricular-subventricular zone (V-SVZ) are prone to rapid exhaustion; thus timely, context-dependent neurogenesis demands adaptive signaling among the vast number of neighboring progenitors nestled between the ventricular surface and nearby blood vessels. To dissect adult neuronal lineage progression and regulation, we profiled >56,000 V-SVZ and olfactory bulb (OB) cells by single-cell RNA-sequencing (scRNA-seq). Our analyses revealed the diversity of V-SVZ-derived OB neurons, the temporal dynamics of lineage progression, and a key intermediate NSC population enriched for expression of Notum, which encodes a secreted WNT antagonist. Single Cell Optical Phenotyping and Expression (SCOPE-seq), a technology linking live cell imaging with scRNA-seq, uncovered dynamic control of cell size concomitant with NSC differentiation with Notum+ NSCs at a critical size poised for cell division, and a preference of NOTUM surface binding to neuronal precursors with active WNT signaling. Finally, in vivo pharmacological inhibition of NOTUM significantly expanded neuronal precursor pools in the V-SVZ. Our findings highlight a critical regulatory state during NSC activation marked by NOTUM, a secreted enzyme that ensures efficient neurogenesis by preventing WNT signaling activation in NSC progeny.

neuroscience↗