Biology subjects

Moeller, L.

Publications and source records attributed to Moeller, L..

5 recordsLinked to original sources

bioRxiv2026

Space-for-time substitution reveals partial transferability of marine biodiversity-temperature relationships

Forecasts of biodiversity responses to climate change often rely on space-for-time substitution, in which spatial biodiversity-climate relationships are used to predict biodiversity change through time. Yet this approach is rarely tested directly because long-term biodiversity time series are scarce. Here, we combine global modern and fossil assemblage data of planktonic foraminifera with site-specific sea-surface temperature reconstructions to compare biodiversity-temperature relationships across space and time. Spatial and temporal compositional turnover models showed similar slopes but consistently different intercepts, with spatial models predicting higher turnover across the full temperature gradient. Restricting the spatial comparison to the environmental domain of individual fossil time series reduced, but did not eliminate, this intercept mismatch. For alpha diversity, spatial models more closely recovered the temporal biodiversity-temperature relationship than for compositional turnover. Thus, for the timescales studied here, space-for-time substitution captures the direction of biodiversity change but not its magnitude through time.

ecology↗

bioRxiv2026

Engineered caspases directly rewire mutant Ras to cell death

As central executioners of cell death, caspases that activate exclusively in diseased cells would provide powerful and specific therapeutic agents. Natural caspase regulation exhibits two universal features that facilitate the engineering of such caspases: proximity-induced subunit assembly and modular separation of substrate recruitment from catalysis. Here, we take advantage of these features to engineer "Raspases," split effector caspases that conditionally reconstitute active complexes upon detection of mutant Ras, an oncogene altered in roughly a quarter of all cancers. When delivered as mRNA in lipid nanoparticles, Raspases selectively eliminate Ras-mutant human cancer lines while sparing wild-type cells. The system is built entirely from human protein domains, can be encoded as a single polyprotein, and can be adapted to trigger pyroptosis. Critically, Raspases match or exceed the potency of alternative Ras-targeting interventions in vitro. These results establish retargeted caspases as a generalizable sense-and-kill platform for selective elimination of diseased cells.

synthetic biology↗

bioRxiv2026

Comprehensive Characterization of the Human Neural Stem Cell Line HNSC.100 as a Versatile Model for Neurobiological Research

Studying neural-related questions is inherently challenging due to the limited number of suitable cell models. Here, we characterize a previously reported immortalized human neural stem cell line, HNSC.100, serving as a robust model for a wide range of neurobiological research questions. The cell line expresses key neural stem cell markers, including SOX2, vimentin, nestin, and allows for efficient genetic manipulation. Furthermore, HNSC.100 cells can be differentiated into neurons, astrocytes, and oligodendrocytes, thereby covering a wide spectrum of major neural cell types. We adapted corresponding differentiation protocols and established a comprehensive panel of molecular markers to validate successful differentiation, enabling precise characterization of the resulting cell population. In addition, we provide a complete dataset of RNA expression levels for all detectable genes in HSNC.100 cells. Based on this dataset, we assembled a list of expressed genes implicated in neural disorders that can be studied with this cell line. Together, we present a detailed characterization of the HNSC.100 cell line and provide new tools and reference data to facilitate its use. This resource enables researchers to evaluate the lines suitability for specific applications and to rapidly integrate HNSC.100 cells into their experimental workflows. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/700829v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1eef4e5org.highwire.dtl.DTLVardef@1100f62org.highwire.dtl.DTLVardef@1621481org.highwire.dtl.DTLVardef@305d5b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2025

Engineered protein circuits for cancer therapy

A central challenge in cancer therapy is selectively killing cancer cells while minimizing resistance. Here, we engineer modular protease-based protein circuits that sense mutant RAS, the most frequently mutated oncogene in cancer, and conditionally activate cell death. Delivered transiently as mRNA in lipid nanoparticles (LNPs), circuits selectively eliminated RAS-mutant cancer cells in culture and suppressed aggressive, multifocal RAS-driven liver tumors. Compared to RAS inhibitors, circuits killed cancer cells independently of oncogene addiction, achieved potent cytotoxicity rather than cytostasis, and functioned at low RAS occupancy through catalysis rather than stoichiometric inhibition. Critically, circuits acquired minimal to no resistance under prolonged selection, while remaining potent against prevalent drug-resistance mechanisms including RAS amplification and bypass signaling. Together, these results establish design principles for engineering therapeutic protein circuits and highlight their potential to overcome longstanding limitations of existing therapeutic modalities.

synthetic biology↗

bioRxiv2019

Bacterial cell wall integrity surveillance is connected to peptidoglycan biosynthesis by the essential phosphorylation of ReoM

Peptidoglycan (PG) is the main component of bacterial cell walls and the target for many antibiotics. PG biosynthesis is tightly coordinated with cell wall growth and turnover, and many of these control activities depend upon PASTA-domain containing eukaryotic-like serine/threonine protein kinases (PASTA-eSTK) that sense PG fragments. However, only a few PG biosynthetic enzymes are direct kinase substrates. Here, we identify the conserved ReoM protein as a novel PASTA-eSTK substrate in the Gram-positive pathogen Listeria monocytogenes. Our data show that the phosphorylation of ReoM is essential as it controls ClpCP-dependent proteolytic degradation of the essential enzyme MurA, which catalyses the first committed step in PG biosynthesis. We also identify ReoY as a second novel factor required for degradation of ClpCP substrates. Collectively, our data imply that the first committed step of PG biosynthesis is activated through control of ClpCP protease activity in response to signals of PG homeostasis imbalance.

microbiology↗