Biology subjects

Schrope, J.

Publications and source records attributed to Schrope, J..

5 recordsLinked to original sources

bioRxiv2026

Fibroblast response to burn injury in larval zebrafish mirrors developmental maturation and is inhibited by infiltrating neutrophils

Fibroblasts mediate tissue repair after damage, but aberrant fibroblast behavior in response to injury can result in impaired wound healing. Severe burn injury often results in tissue scarring, but the underlying mechanisms by which fibroblasts respond to burn injury and the role of inflammation in fibrosis are not well understood. Here we developed fluorescent reporters of collagen expressing mesenchymal cells enabling real time imaging of fibroblasts during homeostatic development and in response to burn injury using larval zebrafish. We find that fibroblasts derived from the mesenchyme respond to burn injury by engaging in a maturation process, characterized by the expression of vimentin, which is reminiscent of larval development. In burned tissue, fibroblast maturation is perturbed by prolonged neutrophil infiltration, resulting in disorganized extracellular matrix (ECM) and delayed ECM remodeling, which can be rescued by neutrophil depletion. This work adds to our understanding of fibroblast development in zebrafish and shows that collagen expressing mesenchymal cells regulate ECM remodeling in coordination with immune cells during burn wound healing. Summary StatementVimentin-positive fibroblasts are required for normal wound healing in larval zebrafish, but the presence of inflammatory neutrophils after burn injury impairs fibroblast maturation and collagen remodeling.

Developmental Biology↗

bioRxiv2024

Co-zorbs: Motile, multispecies biofilms aid transport of diverse bacterial species

Biofilms are three-dimensional structures containing one or more bacterial species embedded in extracellular polymeric substances. Although most biofilms are stationary, Flavobacterium johnsoniae forms a motile spherical biofilm called a zorb, which is propelled by its base cells and contains a polysaccharide core. Here, we report formation of spatially organized, motile, multispecies biofilms, designated "co-zorbs," that are distinguished by a core-shell structure. F. johnsoniae forms zorbs whose cells collect other bacterial species and transport them to the zorb core, forming a co-zorb. Live imaging revealed that co-zorbs also form in zebrafish, thereby demonstrating a new type of bacterial movement in vivo. This discovery opens new avenues for understanding community behaviors, the role of biofilms in bulk bacterial transport, and collective strategies for microbial success in various environments. Significance StatementThis paper reports the discovery of co-zorbs, which are spherical aggregates of bacteria that move and transport other bacteria. Zorbs move toward other bacteria and collect them in a manner reminiscent of phagocytes. Once inside the zorb, the new species form a striking, organized core. The discovery of co-zorbs introduces an entirely new type of bacterial movement and transport involving cooperation among bacterial species. Co-zorbs have potential for engineering microbial systems for biotechnology applications and for managing spread of bacterial pathogens in their hosts.

microbiology↗

bioRxiv2024

Live imaging in zebrafish reveals tissue-specific strategies for amoeboid migration

Amoeboid cells like leukocytes can enter and migrate within virtually every tissue of the body, even though tissues vary widely in their chemical and mechanical composition. Here, we imaged motile T cells as they colonized peripheral tissues during zebrafish development to ask if cells tailor their migration strategy to their local tissue environment. We found that T cells in most sites migrated with f-actin-rich leading-edge pseudopods, matching how they migrate in vitro. T cells notably deviated from this strategy in the epidermis, where they instead migrated using a rearward concentration of f-actin and stable leading-edge blebs. This mode of migration occurs under planar confinement in vitro, and we correspondingly found the stratified keratinocyte layers of the epidermis impose planar-like confinement on leukocytes in vivo. By imaging the same cell type across the body, our data collectively indicates that cells adapt their migration strategy to navigate different tissue geometries in vivo.

cell biology↗

bioRxiv2021

Stromal architecture directs early dissemination in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is an extremely metastatic and lethal disease. Here in both murine and human PDA we demonstrate that extracellular matrix architecture regulates cell extrusion and subsequent invasion from intact ductal structures through Tumor-Associated Collagen Signatures (TACS), resulting in early dissemination from histologically pre-malignant lesions and continual invasion from well-differentiated disease. Furthermore, we show that pancreatitis results in invasion-conducive architectures, thus priming the stroma prior to malignant disease. Analysis in novel microfluidics-derived microtissues and in vivo demonstrates decreased extrusion and invasion following focal adhesion kinase (FAK) inhibition, consistent with decreased metastasis. Thus, data suggest that targeting FAK or strategies to re-engineer and normalize tumor microenvironments, may have a role not only in also in very early disease but also for limiting continued dissemination from unresectable disease. Likewise, it may be beneficial to employ stroma targeting strategies to resolve precursor diseases such as pancreatitis in order to remove stromal architectures that increase risk for early dissemination. Impact StatementCollagen architectures in the tumor stroma facilitate dissemination of carcinoma cells from the earliest histologically "pre-malignant" lesions and continue to promote disease spread from well-differentiated PDA.

cancer biology↗

bioRxiv2020

Under-oil autonomously regulated oxygen microenvironments for cell culture

Oxygen levels in vivo are autonomously regulated by a supply-demand balance, which can be altered in disease states. However, the oxygen levels of in vitro cell culture systems, particularly microscale cell culture, are typically dominated by either supply or demand. Further, the oxygen microenvironment in these systems are rarely monitored or reported. Here, we present a method to establish and dynamically monitor autonomously regulated oxygen microenvironments (AROM) using an oil overlay in an open microscale cell culture system. Using this method, the oxygen microenvironment is dynamically regulated via a supply-demand balance of the system. We simulate the kinetics of oxygen diffusion in multiliquid-phase microsystems on COMSOL Multiphysics and experimentally validate the method using a variety of cell types including mammalian, fungal and bacterial cells. Finally, we demonstrate the utility of this method to establish a co-culture between primary intestinal epithelial cells and a highly prevalent human gut species Bacteroides uniformis.

bioengineering↗