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Rupp, S.

Publications and source records attributed to Rupp, S..

11 recordsLinked to original sources

Cross-Species Biomechanical Determinants of Shape Diversity

How complex molecular mechanisms translate into diverse multicellular shapes remains unclear. By leveraging the bi-layered architecture of six cnidarian species that diverged 500 million years ago, we show that modularity in supracellular mechanics governs larval shape diversity. Using active surface theory, quantitative imaging, and an inducible genetic system, we identify species-specific variations in three biomechanical modules. Basally aligned stress fibers drive axial elongation, while oral geometry and aboral rigidity define shape polarity. Remarkably, manipulating these modules transforms one species shape into another, demonstrating the causal relationship between module variation and shape diversity. Our analysis also uncovers instances of mechanical redundancies, where distinct module combinations generate similar shapes. These findings provide a general framework for how molecular complexity funnels into mesoscale mechanical determinants shaping morphological diversity.

developmental biology↗

Symbiont-specific uptake is mediated by integrins in cnidarian larvae

The symbiotic relationship between dinoflagellate algae and their cnidarian hosts is fundamental to the health of coral reefs. The selection of appropriate symbionts is paramount for the host to gain valuable nutrients and could be tailored to increase stress tolerance against anthropogenic induced changes in ocean environments, such as coral bleaching in response to ocean warming. Previous research suggests glycan-lectin interactions play a role in symbiont uptake; however, blockage of such interactions does not fully inhibit symbiosis establishment, suggesting other receptors are at play. Potential candidates include RGD peptide binding integrins, which are known to mediate phagocytosis of microbes in other systems. Here, we used a combination of cnidarian model systems and human cell lines to determine if integrins facilitate symbiont recognition and uptake. Integrins are highly expressed in the endodermal tissue of the host, where symbiosis takes place, and upon uptake into endodermal cells, symbionts altered the expression of integrins and downstream signaling molecules. Blockage of integrin binding sites with RGD competitor peptides reduced symbiont uptake, but had no effect on the general uptake of non-symbiotic algae, or uptake in a non-symbiotic cnidarian. In addition, inert beads coated with integrin RGD peptide ligands were phagocytosed more readily than beads coated with scrambled peptide. Finally, overexpression of RGD-binding integrins in human cells increased symbiont uptake and mutation of the active binding site abolished uptake. Our findings reveal RGD-binding integrins as key players in symbiosis establishment and shed light on the evolutionary functions of integrins as phagocytic receptors. Significance statementCorals engage in a symbiotic partnership with photosynthetic algae to survive in challenging environments. To date it is largely unclear how the two partners recognize each other. Using a comparative model systems approach, we have identified evolutionary conserved integrins as molecular receptors for specifically engulfing symbionts, but not other algae. This suggests that integrins allow the host to distinguish between symbiotic and non-symbiotic algae and preferentially take up symbionts. Our findings establish a new paradigm for symbiosis establishment in corals and shed light on the ancient function of integrins as environmental sensors.

cell biology↗

A predatory gastrula leads to symbiosis-independent settlement in Aiptasia

The planulae larvae of cnidarians (jellyfish, hydras, anemones, corals) have attracted interest since Haeckels 150-year-old postulation of the gastrula developmental stage of sponges and corals as the terminal lifeform of primitive multicellular metazoans. Widely viewed as primarily particle feeders, the planulae larvae of the anemone Exaiptasia pallida (commonly Aiptasia) have not been reported to undergo settlement and metamorphosis to adult morphology, and the lack of a closed lifecycle has been a major obstacle in this increasingly popular model system for coral-dinoflagellate endosymbiosis. Here we studied Aiptasia larvae feeding behavior and show its indispensability to trigger the first reports of settlement and metamorphosis in the system, finally closing the Aiptasia lifecycle. Surprisingly, the young gastrula-like planulae at just two days post fertilization actively feed on living crustacean nauplii, preferentially to heat-killed ones. Predation is dependent on functional stinging cells (nematocytes), indicative of complex neuronal control. Larvae fed daily dramatically increase in size and at 14 days post fertilization begin to morphologically change prior to settlement at high efficiency. Strikingly, dinoflagellate endosymbionts are neither required for larval growth nor measurably affect settlement dynamics, but are essential for spawning of the mature adult polyps. Our data show for the first time that gastrula-like planulae were capable of prey capture, suggesting carnivory in addition to filter feeding as a common strategy of this terminal life form. These data are discussed in the context of recent revelations on the evolution of basal metazoans.

zoology↗

Cancer Prevalence Across Vertebrates

Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Petos Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer. Statement of SignificanceEvolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes.

cancer biology↗

Proline catabolism is key to facilitating Candida albicans pathogenicity

Candida albicans, the primary etiology of human mycoses, is well-adapted to catabolize proline to obtain energy to initiate morphological switching (yeast to hyphal) and for growth. We report that put1-/- and put2-/- strains, carrying defective Proline UTilization genes, display remarkable proline sensitivity with put2-/- mutants being hypersensitive due to the accumulation of the toxic intermediate P5C, which inhibits mitochondrial respiration. The put1-/- and put2-/- mutations attenuate virulence in Drosophila and murine candidemia models. Using intravital 2-photon microscopy and label-free non-linear imaging, we visualized the initial stages of C. albicans cells colonizing a kidney in real-time, directly deep in the tissue of a living mouse, and observed morphological switching of wildtype but not of put2-/- cells. Multiple members of the Candida species complex, including C. auris, are capable of using proline as a sole energy source. Our results indicate that a tailored proline metabolic network tuned to the mammalian host environment is a key feature of opportunistic fungal pathogens.

microbiology↗

Unexpected higher convergence of human-great ape enteric viromes in central African forest than in a European zoo: A One Health analysis

Human-animal pathogenic transmissions threaten both human and animal health, and the processes catalyzing zoonotic spillover and spillback are complex. Prior field studies offer partial insight into these processes but overlook animal ecologies and human perceptions and practices facilitating human-animal contact. Conducted in Cameroon and a European zoo, this holistic study elucidates these processes, integrating metagenomic, historical, anthropological and great ape ecological analyses, and real-time evaluation of human-great ape contact types and frequencies. Surprisingly, we find more enteric virome sharing between Cameroonian humans and great apes than in the zoo, a virome convergence between Cameroonian humans and gorillas, and adenovirus and enterovirus taxa as most frequently shared between Cameroonian humans and great apes. In addition to physical contact from hunting, meat handling and fecal exposure, overlapping human cultivation and gorilla pillaging in forest gardens explain these unexpected findings. Our multidisciplinary study identifies environmental co-use as a complementary mechanism for viral sharing.

molecular biology↗

The tuatara genome: insights into vertebrate evolutionfrom the sole survivor of an ancient reptilian order

The tuatara (Sphenodon punctatus), the only living member of the archaic reptilian order Rhynchocephalia (Sphenodontia) once widespread across Gondwana, is an iconic and enigmatic terrestrial vertebrate endemic to New Zealand. A key link to the now extinct stem reptiles from which dinosaurs, modern reptiles, birds and mammals evolved, the tuatara provides exclusive insights into the ancestral amniotes. The tuatara genome, at [~]5 Gbp, is among the largest vertebrate genomes assembled. Analysis of this genome and comparisons to other vertebrates reinforces the uniqueness of the tuatara. Phylogenetic analyses indicate tuatara diverged from the snakes and lizards [~]250 MYA. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Genome sequence analysis identifies expansions of protein, non-protein-coding RNA families, and repeat elements, the latter of which show an extraordinary amalgam of reptilian and mammalian features. Sequencing of this genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. It also provides important insights into both the technical challenges and the cultural obligations associated with genome sequencing.

genomics↗

Dinoflagellate symbionts escape vomocytosis by host cell immune suppression

Emergence of the symbiotic lifestyle fostered the immense diversity of all ecosystems on Earth, but symbiosis plays a particularly remarkable role in marine ecosystems. Photosynthetic dinoflagellate endosymbionts power reef ecosystems by transferring vital nutrients to their coral hosts. The mechanisms driving this symbiosis, specifically those which allow hosts to discriminate between beneficial symbionts and pathogens, are not well understood. Here, we uncover that host immune suppression is key for dinoflagellate endosymbionts to avoid elimination by the host using a comparative, model systems approach. Unexpectedly, we find that the clearance of non-symbiotic microalgae occurs by non-lytic expulsion (vomocytosis) and not intracellular digestion, the canonical mechanism used by professional immune cells to destroy foreign invaders. We provide evidence that suppression of TLR signalling by targeting the conserved MyD88 adapter protein has been co-opted for this endosymbiotic lifestyle, suggesting that this is an evolutionarily ancient mechanism exploited to facilitate symbiotic associations ranging from coral endosymbiosis to the microbiome of vertebrate guts.

microbiology↗

Coordination of transcriptional and translational regulations in human cells infected by Listeria monocytogenes

The invasion of mammalian cells by intracellular bacterial pathogens reshuffles their gene expression and functions; however, we lack dynamic insight into the distinct control levels that shape the host response. Here, we have addressed the respective contribution of transcriptional and translational regulations during a timecourse of infection of human intestinal epithelial cells by an epidemic strain of Listeria monocytogenes, using transcriptome analysis paralleled with ribosome profiling. Upregulations were dominated by early transcriptional activation of pro-inflammatory genes, whereas translation inhibition appeared as the major driver of downregulations. Instead of a widespread but transient shutoff, translation inhibition affected specifically and durably transcripts encoding components of the translation machinery harbouring a 5-terminal oligopyrimidine motif. Pre-silencing the most repressed target gene (PABPC1) slowed down the intracellular multiplication of Listeria monocytogenes, suggesting that the infected host cell can benefit from the repression of genes involved in protein synthesis and thereby better control infection.

molecular biology↗

Nutrient-dependent mTORC1 signaling in coral-algal symbiosis

To coordinate development and growth with nutrient availability, animals must sense nutrients and acquire food from the environment once energy is depleted. A notable exception are reef-building corals that form a stable symbiosis with intracellular photosynthetic dinoflagellates (family Symbiodiniaceae (LaJeunesse et al., 2018)). Symbionts reside in symbiosomes and transfer key nutrients to support nutrition and growth of their coral host in nutrient-poor environments (Muscatine, 1990; Yellowlees et al., 2008). To date, it is unclear how symbiont-provided nutrients are sensed to adapt host physiology to this endosymbiotic life-style. Here we use the symbiosis model Exaiptasia pallida (hereafter Aiptasia) to address this. Aiptasia larvae, similar to their coral relatives, are naturally non-symbiotic and phagocytose symbionts anew each generation into their endodermal cells (Bucher et al., 2016; Grawunder et al., 2015; Hambleton et al., 2014). Using cell-specific transcriptomics, we find that symbiosis establishment results in downregulation of various catabolic pathways, including autophagy in host cells. This metabolic switch is likely triggered by the highly-conserved mTORC1 (mechanistic target of rapamycin complex 1) signaling cascade, shown to integrate lysosomal nutrient abundance with animal development (Perera and Zoncu, 2016). Specifically, symbiosomes are LAMP1-positive and recruit mTORC1 kinase. In symbiotic anemones, mTORC1 signaling is elevated when compared to non-symbiotic animals, resembling a feeding response. Moreover, symbiosis establishment enhances lipid content and cell proliferation in Aiptasia larvae. Challenging the prevailing belief that symbiosomes are early arrested phagosomes (Mohamed et al., 2016), we propose a model in which symbiosomes functionally resemble lysosomes as core nutrient sensing and signaling hubs that have co-opted the evolutionary ancient mTORC1 pathway to promote growth in endosymbiotic cnidarians.

cell biology↗

Understanding the evolution of anisogamy in the early diverging fungus, Allomyces

Gamete size dimorphism between sexes (anisogamy) is predicted to have evolved from an isogamous system in which sexes have equal-sized, monomorphic gametes. Although adaptive explanations for the evolution of anisogamy abound, we lack comparable insights into molecular changes that bring about the transition from monomorphism to dimorphism. The basal fungal clade Allomyces provides unique opportunities to investigate genomic changes that are associated with this transition in closely related species that show either isogamous or anisogamous mating systems. The anisogamous species show sexual dimorphism in gamete size, number, pigmentation and motility. We sequenced transcriptomes of five Allomyces isolates representing the two mating systems, including both male and female phenotypes in the anisogamous species. Maximum likelihood ancestral character state reconstruction performed in MESQUITE using the de-novo assembled transcriptomes indicated that anisogamy likely evolved once in Allomyces, and is a derived character as predicted in theory. We found that sexual stages of Allomyces express homologs of several genes known to be involved in sex determination in model organisms including Drosophila and humans. Furthermore, expression of CatSper homologs in male- and female-biased samples in our analysis support the hypothesis that gamete interaction in the anisogamous species of Allomyces may involve similar molecular events as the egg-sperm interaction in animals, including humans. Although the strains representing either mating system shared much of the transcriptome, supporting recent common ancestry, the analysis of rate of evolution using individual gene trees indicates high substitution rates and divergence between the strains. In summary, we find that anisogamy likely evolved once in Allomyces, using convergent mechanisms to those in other taxa.

evolutionary biology↗