Biology subjects

Emery, M. A.

Publications and source records attributed to Emery, M. A..

5 recordsLinked to original sources

bioRxiv2026

Bacterial-driven development is mediated by Calcium-Dependent Intrinsic Apoptosis in the Squid-Vibrio Symbiosis

The presence of beneficial microbes serves as a post-embryonic developmental cue in a wide array of metazoan species. However, the mechanisms through which mutualistic bacteria induce developmental processes such as apoptosis are poorly understood. A leading model system utilized to study bacteria-induced developmental apoptosis is the Hawaiian bobtail squid, Euprymna scolopes, whose bacterial symbiont Vibrio fischeri induces several developmental events upon colonization of the squids light organ. Upon hatching the light organ possesses ciliated epithelial fields (CEFs) and appendages that facilitate the collection of V. fischeri from the ambient seawater for symbiont colonization of the internal crypt spaces. To better understand the molecular pathways underpinning bacterial-induced development occurring in these appendages, we isolated appendages from hatchling (0-1h) and aposymbiotic and symbiotic E. scolopes light organs (18h) for RNA sequencing. Our analysis of this transcriptomic dataset indicated that symbiotic appendages undergo intrinsic apoptosis in response to excessive cytosolic calcium. Further experiments found that symbiotic appendages exhibited increased cytosolic calcium and mitochondrial membrane potential overload relative to their aposymbiotic counterparts. In comparing our appendage specific gene expression to previously published whole light organ transcriptomic dataset, we identified increased presence of apoptosis inducing factor (AIF) and decreased expression of transcripts related to protein folding in the appendages as potential mechanisms of apoptotic signal specificity to the CEF. Together, these data suggest a central role of cytosolic calcium in the developmental apoptotic signaling induced by V. fischeri colonization of the E. scolopes light organ. ImportanceBacterial cues are known to induce post-embryonic animal development, but the mechanisms mediating crosstalk between bacterial product recognition and developmental dynamics require further study. Because of its binary nature and clear developmental phenotypes, the Euprymna scolopes- Vibrio fischeri system is an excellent model for symbiont-induced development. Here, we characterize the symbiont-induced apoptotic signaling that mediates the loss of V. fischeri recruitment structures in the E. scolopes light organ following colonization. Transcriptomic changes in colonized light organs and subsequent microscopy-based experiments support that acquisition of V. fischeri induces loss of the ciliated symbiont recruitment structures in juvenile light organs via intrinsic apoptotic signaling initiated by excess cytosolic calcium. This work advances our understanding of how mutualistic bacterial cues initiate signal transduction to induce developmental programming and may serve as a foundation upon which we can begin to disentangle the ways in which more diverse and complex microbial communities influence post-embryonic development.

developmental biology↗

bioRxiv2026

Differential acquisition of cocaine and heroin self-administration in a rat model of internalizing versus externalizing temperament

Substance Use Disorders (SUDs) constitute a major and rising public health concern. In addition, there is a growing appreciation that different classes of addictive substances are likely to lead to qualitatively different types of SUDs requiring differing treatment and relapse prevention strategies to be most effectively managed. Biological temperament, particularly on the internalizing - externalizing axis, is well established to influence addiction susceptibility. Externalizing behavior has long been understood to predispose individuals to addiction through novelty-seeking, sensation-seeking and impulsivity, while internalizing behavior provides an alternate pathway into addiction via increased occurrence of comorbid disorders (anxiety, depression). Here, we utilize a selectively bred rat model of internalizing vs externalizing temperament (bred High Responders, representing genetically mediated externalizing behavior and bred Low Responders, representing internalizing behavior) to examine differences in the acquisition of self-administration of the prototypical psychostimulant cocaine and the prototypical opioid heroin (diacetylmorphine). We found that, as predicted, cocaine and heroin drove different patterns of acquisition in the two different bred lines of rats. Further, this was influenced by temperament in complex ways. Notably, in females the "telescoping effect" for opioid addiction-like behavior was primarily specific to externalizing temperament. These findings highlight the impact and interaction of many factors, including drug class, temperament, and sex, on the acquisition of drug-taking behavior. Additionally, these findings indicate that sex differences in addiction vulnerability may be influenced in part by biological temperament.

animal behavior and cognition↗

bioRxiv2026

Genetic Architecture of Addiction-Relevant Behaviors in Outbred Sprague-Dawley Rats Reveals Loci for Anxiety-Like and Nociceptive Traits

Studies have shown that substance use liability is associated with novelty seeking, anxiety-like behavior, and pain sensitivity. We examined whether common genetic variation in outbred Sprague-Dawley rats explained variation in behavioral measures from three assays with established links to substance use: locomotor response to a novel environment, elevated plus maze, and tail flick. We estimated single-nucleotide polymorphism heritability and performed genome-wide association analyses using permutation-derived significance thresholds (N=534-654 rats across traits). Heritability estimates ranged from 0.14-0.38 across eleven traits. Three independent loci were identified: chromosome 1 for elevated plus maze open-arm behavior (=0.05), chromosome 14 for elevated plus maze immobility (=0.10), and chromosome 17 for tail flick latency (=0.05). Candidate genes included Slc18a2, Gfra1, and Pdzd8 (chromosome 1); Rel and Bcl11a (chromosome 14); and Eci2 and Eci3 (chromosome 17). We compared these loci with our genome wide association study of a F2 intercross of selectively bred high- and low-responder rats, originally derived from Sprague-Dawleys, that model individual differences in externalizing and internalizing behavior. The current loci are distinct from the ones identified in the bred lines. This difference likely reflects selection history in the high- and low-responder F2s, which focused on facets of exploratory locomotion, while loci for anxiety and pain sensitivity traits were identified in the outbreds. This highlights the benefit of using both outbred and selectively bred rats to probe causal variants contributing to individual differences in substance use liability. The current outbred findings implicate monoaminergic signaling, transcriptional control, and lipid metabolism as testable mechanisms for addiction-relevant behaviors.

genetics↗

bioRxiv2024

Characterizing gene expression profiles of various tissue states in stony coral tissue loss disease using a feature selection algorithm

Stony coral tissue loss disease (SCTLD) remains a substantial threat to coral reef diversity already threatened by global climate change. Restoration efforts and effective treatment of SCTLD requires an in-depth understanding of its pathogenesis in the coral holobiont as well as mechanisms of disease resistance. Here, we present a supervised machine learning framework to describe SCTLD progression in a major reef-building coral, Montastraea cavernosa, and its dominant algal endosymbiont, Cladocopium goreaui. Utilizing support vector machine recursive feature elimination (SVM-RFE) in conjunction with differential expression analysis, we identify a subset of biologically relevant genes that exhibit the highest classification performance across three types of coral tissues collected from a natural reef environment: apparently healthy tissue on an apparently healthy colony, apparently healthy tissue on a SCTLD-affected colony, and lesion tissue on a SCTLD-affected colony. By analyzing gene expression signatures associated with these tissue health states in both the coral host and its algal endosymbiont (family Symbiodiniaceae), we describe key processes involved in SCTLD resistance and disease progression within the coral holobiont. Our findings further support evidence that SCTLD causes dysbiosis between the coral host and its Symbiodinaiceae and additionally describes the metabolic and immune shifts that occur as the holobiont transitions from a healthy to a diseased state. This supervised machine learning framework offers a novel approach to accurately assess the health states of endangered coral species and brings us closer to developing effective solutions for disease monitoring and intervention. AUTHOR SUMMARYCoral reefs are under increasing threat due to climate change, with rising ocean temperatures and disease outbreaks accelerating reef degradation. Stony coral tissue loss disease (SCTLD) has been particularly destructive, leading to widespread coral mortality across Floridas Coral Reef and the wider Caribbean since its emergence in 2014. While the cause of SCTLD remains unknown, the rapid decline in coral reef health highlights the urgent need for innovative approaches to understanding threats to coral health. In this study, we applied a supervised machine learning approach, previously used in cancer research, to identify key genes associated with SCTLD progression in the coral Montastraea cavernosa and its symbiotic algae, which the coral relies on to meet its nutritional requirements. By analyzing gene expression patterns across tissues representing different health states, we find that SCTLD affects the metabolic interactions between the coral and their symbionts and causes shifts in coral immune signaling pathways, even in tissue on a SCTLD-affected colony that appears to be healthy. This study presents a novel framework for applying supervised machine learning in coral gene expression research and could lead to new methods for monitoring coral health and combatting SCTLD.

genomics↗

bioRxiv2022

Effect of selective lesions of nucleus accumbens μ-opioid receptor-expressing cells on heroin self-administration in male and female rats: a study with novel Oprm1-Cre knock-in rats

The brain {micro}-opioid receptor (MOR) is critical for the analgesic, rewarding, and addictive effects of opioid drugs. However, in rat models of opioid-related behaviors, the circuit mechanisms of MOR-expressing cells are less known because of a lack of genetic tools to selectively manipulate them. We introduce a CRISPR-based Oprm1-Cre knock-in transgenic rat that provides cell-type specific genetic access to MOR-expressing cells. After performing anatomical and behavioral validation experiments, we used the Oprm1-Cre knock-in rats to study the role of nucleus accumbens (NAc) MOR-expressing cells in heroin self-administration in male and female rats. Using RNAscope, autoradiography, and fluorescence in situ hybridization chain reaction (HCR-FISH), we found no differences in Oprm1 expression in NAc, dorsal striatum (DS), and dorsal hippocampus, or MOR receptor density (except DS) or function between Oprm1-Cre knock-in rats and wildtype littermates. HCR-FISH assay showed that iCre is highly co-expressed with Oprm1 (95-98%). There were no genotype differences in pain responses, morphine analgesia and tolerance, heroin self-administration, and relapse-related behaviors. We used the Cre-dependent vector AAV1-EF1a-Flex-taCasp3-TEVP to lesion NAc MOR-expressing cells and report sex-specific effects: the lesions decreased acquisition of heroin self-administration in male Oprm1-Cre rats and had a stronger inhibitory effect on the effort to self-administer heroin in female Oprm1-Cre rats. The validation of an Oprm1-Cre knock-in rat enables new strategies for understanding the role of MOR-expressing cells in rat models of opioid addiction, pain-related behaviors, and other opioid-mediated functions. Our initial mechanistic study with these rats suggests a sex-specific role of NAc MOR-expressing cells in heroin self-administration. Significance statementThe brain {micro}-opioid receptor (MOR) is critical for the analgesic, rewarding, and addictive effects of opioid drugs. However, in rat models of opioid-related behaviors, the circuit mechanisms of MOR-expressing cells are less known because of a lack of genetic tools to selectively manipulate them. We introduce a CRISPR-based Oprm1-Cre knock-in transgenic rat that provides cell-type specific genetic access to brain MOR-expressing cells. After performing anatomical and behavioral validation experiments, we used the Oprm1-Cre knock-in rats to show a potential sex-specific role of nucleus accumbens MOR-expressing cells in heroin self-administration. The new Oprm1-Cre rats can be used to study both the general and sex-specific role of brain MOR-expressing cells in animal models of opioid addiction, pain-related behaviors, and other opioid-mediated functions.

neuroscience↗