Biology subjects

Garrison, J. L.

Publications and source records attributed to Garrison, J. L..

4 recordsLinked to original sources

bioRxiv2025

A FMRF-amide peptide that regulates cell non-autonomous protein homeostasis in C. elegans.

The coordination of protein homeostasis from the brain to periphery is essential for the health and survival of all animals. In C. elegans, glia serve a central role in coordinating organismal protein homeostasis and longevity via the unfolded protein response of the endoplasmic reticulum (UPRER). However, the full extent of the cell non-autonomous response and the identity of the signaling molecules required remained unknown. Here, we show that glial UPRER activation induces robust transcriptomic changes in specific tissue types across the animal, particularly in pathways related to neuropeptide signaling. We performed neuropeptidomics and loss and gain-of-function genetic screens and identified a single neuropeptide, FLP-17, that is sufficient but not necessary to induce cell non-autonomous activation of the UPRER. FLP-17 is sufficient to protect against chronic ER stress and age-dependent protein aggregation. We determined that FLP-17 acts through the receptor, EGL-6, to activate cell non-autonomous UPRER. This work reveals a complex peptidergic signaling network initiated by glial activation of the UPRER to regulate organismal protein homeostasis.

neuroscience↗

bioRxiv2024

Aging disrupts spatiotemporal coordination in the cycling ovary

Throughout the female reproductive lifespan, the ovary completes hundreds of cycles of follicle development, ovulation, and tissue regeneration1-3. These processes rely on the precisely coordinated intricate multicellular interactions across time and space4. How aging disrupts these interactions, leading to an overall decline in reproductive and endocrine functions, remains understudied. To understand the multicellular dynamics that underlie ovarian function and their changes with age, here we use Slide-seq, a near-cellular spatial transcriptomics method, to profile 22 mouse ovaries across the reproductive cycle and chronological age, representing 610,620 near-cellular spots across 69 spatial transcriptomic profiles5,6. We develop a segmentation analysis to identify spatial niches that capture different states of folliculogenesis from static snapshots in situ, allowing us to examine the multicellular dynamics of 358 oocytes, 668 follicles, and 236 corpora lutea. We find that aging disrupts both the spatial organization and temporal coordination of folliculogenesis before the cessation of cycling, which may contribute to the dysregulation of hormone production and signaling. These disruptions are marked by altered immune cell dynamics, inflammatory signaling, and global tissue disorganization that impair the cyclic remodeling required for ovarian function. Our findings reveal how multicellular niches orchestrate ovarian function and demonstrate how age-related breakdown of tissue organization across time and space precedes reproductive decline.

genomics↗

bioRxiv2024

Dysregulation of the fluid homeostasis system by aging

Chronic dehydration is a leading cause of morbidity for the elderly, but how aging alters the fluid homeostasis system is not well understood. Here, we used a combination of physiologic, behavioral and circuit analyses to characterize how fluid balance is affected by aging in mice. We found that old mice have a primary defect in sensing and producing the anti-diuretic hormone vasopressin, which results in chronic dehydration. Recordings and manipulations of the thirst circuitry revealed that old mice retain the ability to sense systemic cues of dehydration but are impaired in detecting presystemic, likely oropharyngeal, cues generated during eating and drinking, resulting in disorganized drinking behavior on short timescales. Surprisingly, old mice had increased drinking and motivation after 24-hour water deprivation, indicating that aging does not result in a general impairment in the thirst circuit. These findings reveal how a homeostatic system undergoes coordinated changes during aging.

neuroscience↗

bioRxiv2021

Cold survival and its molecular mechanisms in a locally adapted nematode population

Since Darwin, evolutionary biologists have sought to understand the drivers and mechanisms of natural trait diversity. The field advances toward this goal with the discovery of phenotypes that vary in the wild, their relationship to ecology, and their underlying genes. Here, we established resistance to extreme low temperature in the free-living nematode Caenorhabditis briggsae as an ecological and evolutionary model system. We found that C. briggsae strains of temperate origin were strikingly more cold-resistant than those isolated from tropical localities. Transcriptional profiling revealed expression patterns unique to the resistant temperate ecotype, including dozens of genes expressed at high levels even after multiple days of cold-induced physiological slowdown. Mutational analysis validated a role in cold resistance for seven such genes. As the temperate C. briggsae population likely diverged only ~700 years ago from tropical ancestors, our findings highlight a candidate case of very rapid, robust, and genetically complex adaptation, and shed light on the mechanisms at play.

evolutionary biology↗