Biology subjects

Schupp, P.

Publications and source records attributed to Schupp, P..

2 recordsLinked to original sources

bioRxiv2022

Body-plan reorganization in a sponge correlates with microbiome change

Mounting evidence suggests that animals and their associated bacteria interact via intricate molecular mechanisms, and it is hypothesized that disturbances to the microbiome can influence animal development. Sponges diverged from other animals more than 750 MYA and represent one of the earliest branching animal phyla that exhibit symbiotic relationships with diverse bacteria. Over 41 microbial phyla have been found in association with sponges, forming a holobiont that is integral to aquatic ecosystems worldwide. Sponge-associated microbes contain an enriched set of proteins bearing eukaryotic-like domains, and their metabolism supports the host with nutrients. This indicates strong physiological interconnections in the holobiont, which are thought to be modulated by sponge immunity and pattern-recognition proteins. Despite the hypothesized tight physiological integration and ancient origin of the sponge holobiont, the effect of changes in the symbiotic community on the sponge metabolism and morphogenesis remains poorly understood. Here, we show that the loss of a key microbial sponge symbiont correlates with a stark body plan reorganization of the sponge host. This reorganization is coupled with broad transcriptomic changes and includes the modulation of signaling pathways known to be involved in morphogenesis and innate immune response in sponges and other animals. This study provides a combined genetic, physiological, and morphological assessment of the effect of changes in the microbiome on sponge post-embryonic development and homeostasis. The drastic microbiome reorganization and the correlated response observed in the sponge host provide evidence for a coupling between sponge transcriptomic state and the state of its microbiome. Our results suggest that sponges use molecular mechanisms to respond to changes in their microbiome and that the ability to sense and respond to microbiome perturbations has deep evolutionary origins among animals.

genomics↗

bioRxiv2020

Machine intelligence identifies soluble TNFa as a therapeutic target for spinal cord injury

Traumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair1,2. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining 5 different blinded, fully counter-balanced treatment trials for different acute anti-inflammatory treatments for cervical spinal cord injury in rats. Multi-dimensional discovery, using topological data analysis3 (TDA) and principal components analysis (PCA) revealed that only one showed consistent multidimensional syndromic benefit: intrathecal application of recombinant soluble TNF receptor 1 (sTNFR1), which showed an inverse-U dose response efficacy. Using the optimal acute dose, we showed that clinically-relevant 90 min delayed treatment profoundly affected multiple biological indices of NI in the first 48 hrs after injury, including reduction in pro-inflammatory cytokines and gene expression of a coherent complex of acute inflammatory mediators and receptors. Further, a 90 min delayed bolus dose of sTNFR1 reduced the expression of NI markers in the chronic perilesional spinal cord, and consistently improved neurological function over 6 weeks post SCI. These results provide validation of a novel strategy for precision preclinical drug discovery that is likely to improve translation in the difficult landscape of CNS trauma, and confirm the importance of TNF signaling as a therapeutic target.

neuroscience↗