Biology subjects

Sullivan, K. R.

Publications and source records attributed to Sullivan, K. R..

3 recordsLinked to original sources

bioRxiv2025

Development of long-term oyster tissue cultures reveals cellular plasticity, regenerative potential, and sustained physiological activity

Molluscs are ecologically and economically significant, yet progress in understanding their cellular biology has been constrained by the lack of reliable molluscan cell culture systems. Insights into key molluscan biology such as immunity, biomineralization, and host-pathogen interactions, has previously been limited by short term survival of primary culture systems. Here, we establish reproducible long-term in vitro and ex vivo cultures of cells and tissues from the oyster, Ostrea edulis, including whole heart, visceral mass, mantle, and gill explants. Explanted tissues remained viable for over two months, with whole hearts maintaining rhythmic, stimulus-responsive contractions for up to nine months. Cultures maintained structural and functional features while uncovering cellular plasticity, including haemocyte granule turnover, auricular epithelial remodelling with novel ciliation, and the emergence of de novo multicellular microtissues. Previously under-characterized tissue-specific cell types were maintained in culture, including adipocytes from the visceral mass and myocytes from the mantle, thereby expanding the cellular repertoire accessible in vitro. Mineralized structures were observed across tissue cultures, highlighting the potential of this system for studying biomineralization. By sustaining diverse cell types in vitro, these cultures provide a novel tractable platform for studying molluscan diseases, while also laying the foundation for deeper investigation into comparative invertebrate biology and the development of immortalised molluscan cell lines.

cell biology↗

bioRxiv2024

dArc1 controls sugar reward valuation in Drosophila melanogaster

The Arc genes -- which include Drosophila Arc1 and Arc2 (dArc) -- evolved from Ty3 retrotransposons and encode proteins that form virus-like capsids. These capsids enable a novel form of intercellular communication by transferring RNAs between cells. However, the specific neuronal circuits and brain processes Arc intercellular signaling regulates remain unknown. Here, we show that loss of both dArc genes in Drosophila melanogaster enhances associative learning in an appetitive conditioning paradigm, where flies associate an odor with sugar rewards. This increased learning performance arises from an increased valuation of sugar rewards: unlike wild-type flies, dArc-/- flies form abnormally strong associations even when the sugar reward is small or has no caloric value. We found that the {gamma}5-dopaminergic neurons of the protocerebral anterior medial (PAM) cluster, which encode the positive valence of sugar rewards, show heightened activity in response to sucrose in dArc-/- flies. We further show that the learning phenotype of dArc-/- flies depends on the formation of capsids, underscoring a direct role for capsid-mediated Arc signaling in sugar valuation. Our findings establish dArc genes as critical regulators of reward valuation in D. melanogaster, acting through a non-cell autonomous mechanism that relies on capsid-mediated communication between cells.

neuroscience↗

bioRxiv2024

Arc mediates intercellular tau transmission via extracellular vesicles

Intracellular neurofibrillary tangles that consist of misfolded tau protein1 cause neurodegeneration in Alzheimers disease (AD) and frontotemporal dementia (FTD). Tau pathology spreads cell-to-cell2 but the exact mechanisms of tau release and intercellular transmission remain poorly defined. Tau is released from neurons as free protein or in extracellular vesicles (EVs)3-5 but the role of these different release mechanisms in intercellular tau transmission is unclear. Here, we show that the neuronal gene Arc is critical for packaging tau into EVs. Brain EVs purified from human tau (hTau) transgenic rTg4510 mice (rTgWT) contain high levels of hTau that are capable of seeding tau pathology. In contrast, EVs purified from rTgWT crossed with Arc knock-out mice (rTgArc KO) have significantly less hTau and cannot seed tau aggregation. Arc facilitates the release of hTau in EVs produced via the I-BAR protein IRSp53, but not free tau. Arc protein directly binds hTau to form a fuzzy complex that we identified in both mouse and human brain tissue. We find that pathological intracellular hTau accumulates in neurons in rTgArc KO mice, which correlates with accelerated neuron loss in the hippocampus. Finally, we find that intercellular tau transmission is significantly abrogated in Arc KO mice. We conclude that Arc-dependent release of tau in EVs plays a significant role in intracellular tau elimination and intercellular tau transmission.

neuroscience↗