Biology subjects

Chin, S. M.

Publications and source records attributed to Chin, S. M..

4 recordsLinked to original sources

bioRxiv2026

From recognition to neglect: Molecular and physiological responses to heterospecific pollen decay with evolutionary distance

Post-mating, pre-zygotic (PMPZ) reproductive barriers are often attributed to precise molecular recognition between male and female gametes, yet little is known about how these interactions change as species diverge. In flowering plants, pollen tube growth depends on coordinated signaling between pollen and pistil, raising the question of whether PMPZ barriers arise through active incompatibility mechanisms or gradual loss of pollen-pistil coordination. Here, we combined transcriptomic profiling and pollen tube growth assays across a phylogenetically structured set of crosses in a diverse alpine plant community. We show that the magnitude of the pistillar transcriptomic response to pollination declined quantitatively with evolutionary distance rather than shifting in a binary compatible/incompatible manner. Pollination-associated functional gene ontology categories were strongest in conspecific and intrageneric crosses and weakened with divergence. Heterospecific pollen tubes also grew more slowly than conspecific tubes, with growth rates declining overall with genetic distance. However, the slowest growth occurred in intrageneric crosses, suggesting that close relatives may represent a distinct evolutionary zone where reduced maternal support coincides with additional hindrance mechanisms. Together, these results support a graded, divergence-dependent model of pollen-pistil incongruence driven primarily by attenuation of coordinated growth rather than strict heterospecific rejection.

evolutionary biology↗

bioRxiv2025

Reinvigoration of translational activity in dysfunctional T cells initiates theearly intratumoral response to PD-1 blockade

T cells are key effectors of antitumor responses elicited by PD-1 blockade. However, it remains elusive by which mechanism(s) PD-1 blockade initiates T cell-driven antitumor immunity in cancer tissues. Here, we dissect early T cell reactivation upon anti-PD-1 in patient-derived tumor fragments. Using bispecific antibodies to target anti-PD-1 to individual T cell subsets, we demonstrate that intratumoral CD8+ and CD4+ T cells can independently drive immune remodeling of the tumor microenvironment. The CD8+ and CD4+ T cells that respond to anti- PD-1 exhibit a shared dysfunctional gene program, characterized by tumor-reactivity, terminal exhaustion, effector capacity, and reduced translational activity. Notably, rather than acting through transcriptional rewiring, anti-PD-1 reinvigorates dysfunctional T cells by overcoming this translational barrier, resulting in restored effector function. Altogether, these results reveal dysfunctional T cells as initiators of early tissue responses to PD-1 blockade and identify a novel mode of their therapeutic reinvigoration through restoration of translational control. One Sentence SummaryTranslational reactivation of tumor-residing dysfunctional T cells drives early intratumoral immune activity upon PD-1 blockade.

immunology↗

bioRxiv2020

N-terminal modification of actin by acetylation and arginylation determines the architecture and assembly rate of linear and branched actin networks

The great diversity in actin network architectures and dynamics is exploited by cells to drive fundamental biological processes, including cell migration, endocytosis and cell division. While it is known that this versatility is the result of the many actin-remodeling activities of actin-binding proteins, recent work implicates post-translational modification of the actin N-terminus by either acetylation or arginylation itself as an equally important regulatory mechanism. However, the molecular mechanisms by which acetylation and arginylation alter the properties of actin are not well understood. Here, we directly compare how processing, and modification of the N-terminus of actin affects its intrinsic polymerization dynamics and its remodeling by actin-binding proteins that are essential for cell migration. We find that in comparison to acetylated actin, arginylated actin reduces intrinsic as well as formin-mediated elongation and Arp2/3-mediated nucleation. By contrast, there are no significant differences in Cofilin-mediated severing. Taken together, these results suggest that cells can employ the differently modified actins to precisely regulate actin dynamics. In addition, unprocessed, or non-acetylated actin show very different effects on formin-mediated-elongation, Arp2/3-mediated nucleation, and severing by Cofilin. Altogether, this study shows that the nature of the N-terminus of actin can induce distinct actin network dynamics, which can be differentially used by cells to locally finetune actin dynamics at distinct cellular locations, such as at the leading edge.

biochemistry↗

bioRxiv2019

Cofilin loss in Drosophila muscles contributes to myopathy through defective sarcomerogenesis

Sarcomeres, the fundamental contractile units of muscles, are conserved structures composed of actin thin filaments and myosin thick filaments. How sarcomeres are formed and maintained is not well understood. Here, we show that knockdown of Drosophila Cofilin (DmCFL), an actin depolymerizing factor, leads to the progressive disruption of sarcomere structure and muscle function in vivo. Loss of DmCFL also results in the formation of sarcomeric protein aggregates and impairs sarcomere addition during growth. Strikingly, activation of the proteasome delayed muscle deterioration in our model. Further, we investigate how a point mutation in CFL2 that causes nemaline myopathy (NM) in humans, affects CFL function and leads to the muscle phenotypes observed in vivo. Our data provide significant insights to the role of CFLs during sarcomere formation as well as mechanistic implications for disease progression in NM patients.

developmental biology↗