Biology subjects

Mun, J.

Publications and source records attributed to Mun, J..

7 recordsLinked to original sources

bioRxiv2025

De Novo design of a potent Wnt Surrogate specific for the frizzled7 subtype members

In humans, 19 Wnt ligands interact with 10 Frizzled (Fzd) receptors and the co-receptors LRP5/6 to initiate signaling. Wnts and Fzds are highly promiscuous, making it challenging to dissect the specific outcomes of individual Wnt-Fzd interactions. Developing Wnt surrogates with specificity for individual Fzd subtypes could be pivotal. We present a modular, potent, and Fzd7-specific Wnt surrogate that consists of three de novo designed modules, a Fzd7 binder, an LRP6 binder and a homodimeric protein. The Fzd7-specific module was designed by targeting two less conserved surface patches on the cysteine-rich domain (CRD) of Fzds to achieve both selectivity and affinity. It exhibits a strong binding affinity (KD < 2.3 nM) for the very closely related Fzd7 subtype members (Fzd7, Fzd1, Fzd2) with no measurable binding to the CRDs of the other seven Fzd receptors. This Wnt surrogate induced spheroid organoid formation from intestinal stem cells at subnanomolar concentration, and promoted full hair follicle regeneration and robust hair growth in mice. These results suggest that our strategy could be extended to design modular Wnt surrogates capable of selectively activating individual Fzd receptors, providing a valuable tool kit for development and differentiation, organoid cultures and targeted regeneration.

bioengineering↗

bioRxiv2025

Absence of testes at puberty impacts functional development of nigrostriatal but not mesoaccumbal dopamine terminals in a wild-derived mouse

The nigrostriatal and mesoaccumbal dopamine systems are thought to contribute to changes in behavior and learning during adolescence, yet it is unclear how the rise in gonadal hormones at puberty impacts the function of these systems. We studied the impact of prepubertal gonadectomy on evoked dopamine release in male Mus spicilegus, a mouse whose adolescent life history has been carefully characterized in the wild and laboratory. To examine how puberty impacts the dopamine systems in M. spicilegus males, we removed the gonads prepubertally at P25 and then examined evoked dopamine release in the dorsomedial, dorsolateral, and nucleus accumbens core regions of striatal slices at P60-70. To measure dopamine release, we used near-infrared catecholamine nanosensors (nIRCats) to enable study of spatial distribution of dopamine release sites in each striatal region. We found that prepubertal gonadectomy led to a significantly reduced density of dopamine release sites and reduced dopamine release at each site in the dorsolateral nigrostriatal system compared to sham controls. By contrast, mesoaccumbal dopamine release was comparable between sham and gonadectomized groups. Our data suggest that during adolescence the development of the nigrostriatal dopamine system is significantly affected by the rise in gonadal hormones in males, while the mesoaccumbal system shows no detectable sensitivity at this time point. These data are consistent with molecular studies in rodents that suggest nigrostriatal neurons are sensitive to androgens at puberty, and extend our understanding of how gonadal hormones could impact the spatial distribution and release potential of dopamine terminals in the striatum. Significance StatementHere we use a wild-derived species, Mus spicilegus, to study adolescent development. This wild-derived species has value over standard lab mice because it is more likely to exhibit evolved developmental programs relevant to dispersal and other natural behaviors. By using this wild-derived species and metrics of evoked dopamine release with spatial resolution, we can test if the rise in gonadal hormones at puberty plays a role in maturation of dopamine terminal function in the striatum. These findings may help us better understand developmental programs in humans that orchestrate changes in behavior at adolescent milestones in contexts of both health and disease.

neuroscience↗

bioRxiv2025

Neurochemical imaging reveals changes in dopamine dynamics with photoperiod in a seasonally social vole species

Studying dopamine signaling in non-model organisms is crucial for understanding the broad range of behaviors not represented in traditional model systems. However, exploring new species is often hindered by a scarcity of tools suitable for non-genetic models. In this work, we introduce near-infrared catecholamine nanosensors (nIRCats) to investigate dopamine dynamics in meadow voles, a rodent species that exhibits distinct changes in social behavior and neurobiology across photoperiods. We observe increased dopamine release and release site density in social voles under short photoperiods, suggesting adaptations linked to environmental changes. Moreover, pharmacological and extracellular manipulations demonstrate that social voles exhibit heightened responsiveness to dopamine-increasing interventions and resilience against suppressive conditions. These findings highlight a significant association between dopamine signaling and photoperiod-driven changes in social behavior and establish nIRCats as an effective tool for expanding our understanding of dopamine dynamics across non-model organisms.

neuroscience↗

bioRxiv2024

Antigen-specific T cell immunotherapy by in vivo mRNA delivery

Immunotherapy has shown promise for treating patients with autoimmune diseases or cancer, yet treatment is associated with adverse effects associated with global activation or suppression of T cell immunity. Here, we developed antigen-presenting nanoparticles (APNs) to selectively engineer disease antigen (Ag)-specific T cells by in vivo mRNA delivery. APNs consist of a lipid nanoparticle core functionalized with peptide-major histocompatibility complexes (pMHCs), facilitating antigen-specific T cell transfection through cognate T cell receptor-mediated endocytosis. In mouse models of type 1 diabetes and multiple myeloma, APNs selectively deplete autoreactive T cells leading to durable control of glycemia, and engineer virus-specific T cells with anti-cancer chimeric antigen receptors (CARs), achieving comparable therapeutic outcome as virally transduced ex vivo CAR. Overall, our work supports the use of APNs to engineer disease-relevant T cells in vivo as Ag-specific immunotherapy for autoimmune disorders and cancer.

bioengineering↗

bioRxiv2023

Neural computation in the brainstem for visceral sensation-driven haemodynamics

The brainstem serves as an intermediary processor of haemodynamic sensations via nucleus tractus solitaries (NTS) in regulating circulatory system. After sensing visceral inputs, the NTS relays information to efferent pathways to modulate peripheral viscera. However, the neural computation mechanism underlying how the NTS processes viscerosensory input remains unknown. Here, we show the computational principles embedded inside the NTS of rats, producing haemodynamic modulation in concert. Our findings demonstrate that the collective dynamics leveraging from neuronal population within the NTS neural circuit encode input-driven haemodynamics. The NTS exhibits the neural trajectory, the dynamical trace of neural states, which is confined to low-dimensional latent space and may represent haemodynamic perturbations. Surprisingly, by normalizing neural trajectory of rats, we found the across-rat common rules for the viscerosensory-information processing by the NTS. Furthermore, the common rules allowed to identify inter-subject variable haemodynamics by quantifying the computational mechanisms in neuro-haemodynamic axis. Our findings provide pioneering insights into understanding the neural computation involved in regulation of visceral functions by the autonomic nervous system.

neuroscience↗

bioRxiv2022

Near Infrared Nanosensors Enable Optical Imaging of Oxytocin with Selectivity over Vasopressin in Acute Mouse Brain Slices

Oxytocin plays a critical role in regulating social behaviors, yet our understanding of its role in both neurological health and disease remains incomplete. Real-time oxytocin imaging probes with the spatiotemporal resolution relevant to its endogenous signaling are required to fully elucidate oxytocin function in the brain. Herein we describe a near-infrared oxytocin nanosensor (nIROx), a synthetic probe capable of imaging oxytocin in the brain without interference from its structural analogue, vasopressin. nIROx leverages the inherent tissue-transparent fluorescence of single-walled carbon nanotubes (SWCNT) and the molecular recognition capacity of an oxytocin receptor peptide fragment (OXTp) to selectively and reversibly image oxytocin. We employ these nanosensors to monitor electrically stimulated oxytocin release in brain tissue, revealing oxytocin release sites with a median size of 3 m which putatively represents the spatial diffusion of oxytocin from its point of release. These data demonstrate that covalent SWCNT constructs such as nIROx are powerful optical tools that can be leveraged to measure neuropeptide release in brain tissue.

bioengineering↗

bioRxiv2021

Polymer-Conjugated Carbon Nanotubes for Biomolecule Loading

Nanomaterials have emerged as an invaluable tool for the delivery of biomolecules such as DNA and RNA, with various applications in genetic engineering and post-transcriptional genetic manipulation. Alongside this development, there has been an increasing use of polymer-based techniques, such as polyethyleneimine (PEI), to electrostatically load polynucleotide cargoes onto nanomaterial carriers. However, there remains a need to assess nanomaterial properties, conjugation conditions, and biocompatibility of these nanomaterial-polymer constructs, particularly for use in plant systems. In this work, we develop mechanisms to optimize DNA loading on single-walled carbon nanotubes (SWNTs) with a library of polymer-SWNT constructs and assess DNA loading ability, polydispersity, and both chemical and colloidal stability. Counterintuitively, we demonstrate that polymer hydrolysis from nanomaterial surfaces can occur depending on polymer properties and attachment chemistries, and describe mitigation strategies against construct degradation. Given the growing interest in delivery applications in plant systems, we also assess the toxicity of polymer-based nanomaterials in plants and provide recommendations for future design of nanomaterial-based polynucleotide delivery strategies.

biochemistry↗