Biology subjects

Reese, S.

Publications and source records attributed to Reese, S..

6 recordsLinked to original sources

bioRxiv2026

The Adhesion GPCR Flamingo-Like 1 (FMIL-1) Directs Synapse Formation in a Nociceptive Circuit

The species-specific anatomy of nervous systems suggests that circuit architecture is largely encoded by genetic blueprints. In C. elegans, PVD nociceptive neurons synapse with PVC and AVA interneurons to drive escape responses to noxious stimuli. We used fluorescent markers for PVD synapses with PVC and AVA in a candidate screen to detect connectivity genes. This approach revealed that the LIM homeodomain transcription factor MEC-3 and its target, FMIL-1 (Flamingo-like), function in PVD to direct connectivity with PVC and AVA. FMIL-1 is an adhesion class G Protein-coupled receptor (aGPCR), a protein family with members also implicated in mammalian synapse formation. We show that FMIL-1 acts early in PVD and is also sufficient to induce ectopic synapses in another circuit, thus suggesting that FMIL-1 promotes synaptogenesis. Our work establishes a new experimental circuit in C. elegans for investigating neuronal connectivity and provides evidence that FMIL-1/aGPCRs regulate synapse formation.

neuroscience↗

bioRxiv2026

Quantitative biophysical analysis of human septin hexamer and octamer self-assembly on model membranes

1Septins are GTP-binding cytoskeletal proteins that shape and compartmentalize the plasma membrane. Their complex interactome has made it difficult to understand the molecular factors that govern their assembly. Moreover, it is unclear whether human septin hexamers and octamers form distinct higher-order assemblies, especially at the plasma membrane. Here, we address this question by using label-free methods to probe binding and self-assembly of recombinant human septins on supported lipid bilayers. Quartz crystal microbalance with dissipation (QCM-D) monitoring revealed that septin-membrane binding is diffusion-limited and concentration-dependent. Hexamers and octamers showed distinct viscoelastic properties, suggestive of structural differences. Imaging by atomic force microscopy (AFM) revealed that septin hexamers formed aligned nematic filamentous networks, whereas septin octamers formed aligned curved structures including spirals. QCM-D and AFM measurements both showed that septins form double-layered filament networks. However, upon C-terminal truncation of the SEPT6 and SEPT7 subunits, hexamers no longer bound the membrane while octamers formed a single-layered network of filament spirals. Our findings reveal that human septin hexamers and octamers interact differently with membranes, providing a baseline to understand their functions in the cell. 2 Significance statementO_LISeptins are cytoskeletal proteins that control cell membrane shape and stiffness. It is poorly understood how septin oligomers, the basic building blocks of septin filaments, bind and assemble on membranes. C_LIO_LIWe used label-free biophysical assays to quantitatively compare the binding kinetics and self-assembly behavior of recombinant human septin hexamers and octamers on supported lipid bilayer membranes. C_LIO_LIOur findings reveal that human septin hexamers and octamers both form organized filamentous networks on membranes, but with different structural properties that may potentially translate into different biological functions. C_LI

biophysics↗

bioRxiv2022

Multi-modal digital pathology for colorectal cancer diagnosis by high-plex immunofluorescence imaging and traditional histology of the same tissue section

Precision medicine is critically dependent on better methods for diagnosing and staging disease and predicting drug response. Histopathology using Hematoxylin and Eosin (H&E) stained tissue - not genomics - remains the primary diagnostic method in cancer. Recently developed highly-multiplexed tissue imaging methods promise to enhance research studies and clinical practice with precise, spatially-resolved, single-cell data. Here we describe the "Orion" platform for collecting and analyzing H&E and high-plex immunofluorescence (IF) images from the same cells in a whole-slide format suitable for diagnosis. Using a retrospective cohort of 74 colorectal cancer resections, we show that IF and H&E images provide human experts and machine learning algorithms with complementary information that can be used to generate interpretable, multiplexed image-based models predictive of progression-free survival. Combining models of immune infiltration and tumor-intrinsic features achieves a hazard ratio of [~]0.05, demonstrating the ability of multi-modal Orion imaging to generate high-performance biomarkers.

cancer biology↗

bioRxiv2021

Micafungin-induced Cell Wall Damage Stimulates Microcycle Conidiation in Aspergillus nidulans

Fungal cell wall receptors relay messages about the state of the cell wall to the nucleus through the Cell Wall Integrity Signaling (CWIS) pathway. The ultimate role of the CWIS pathway is to coordinate repair of cell wall damage and to restore normal hyphal growth. Echinocandins such as micafungin represent a class of antifungals that trigger cell wall damage by affecting synthesis of {beta}-glucans, filamentous fungis response to these antifungals are fundamentally unknown. To obtain a better understanding of the dynamics of the CWIS response and its multiple effects, we have coupled dynamic transcriptome analysis with morphological studies of Aspergillus nidulans hyphae responding to micafungin. Our results reveal that expression of the master regulator of asexual development, BrlA, is induced by micafungin exposure. Further study showed that micafungin elicits microcycle conidiation in a BrlA-dependent manner, and that this response is abolished in the absence of MpkA. Our results suggest that microcycle conidiation may be a general response to cell wall perturbation which in some cases would enable fungi to tolerate or survive otherwise lethal damage.

molecular biology↗

bioRxiv2020

Simultaneous Discovery of Positive and Negative Interactions Among Root Microbiome Bacteria Using Microwell Recovery Arrays

Understanding the consequences of microbe-microbe interactions is critical in efforts to predict the function of microbiomes and to manipulate or construct communities to achieve desired outcomes. The investigation of these interactions poses a significant challenge - in part due to the lack of suitable experimental tools. We present the Microwell Recovery Array, a high throughput approach designed to rapidly screen interactions across a microbiome and uncover higher-order combinations of strains that either inhibit or promote the function of a GFP-producing focal species. One experiment generates 104 unique microbial communities that contain a focal species combined with a unique combination of previously uncharacterized cells from plant rhizosphere. Cells are then sequentially extracted from individual co-culture wells that display highest or lowest levels of focal species function using a novel high-resolution photopolymer extraction system. Microbes present are subsequently identified and the putative interactions are validated. Using this approach, we screen the Populus trichocarpa rhizosphere for bacterial strains affecting the survival and growth of Pantoea sp. YR343, a plant growth promoting strain isolated from the P. trichocarpa rhizosphere. We were able to simultaneously isolate and validate multiple Stenotrophomonas strains that antagonize strain YR343 growth and a set of Enterobacter strains that promote strain YR343 growth. The latter demonstrates the unique ability of the platform to uncover multi-membered consortia that generate emergent phenotypes. This knowledge will inform the development of beneficial consortia that promote the production of Populus biofuel feedstock, while the platform is adaptable to screening higher-order interactions in any microbiome of interest. Significance StatementAchieving a fundamental understanding of microbe-microbe interactions that occur within microbial communities is a grand challenge in microbiology due to the limited experimental tools available. In this report, we describe a new tool that enables one to screen microbial interactions across thousands of compositionally unique communities to discover collections of bacteria that antagonize or promote the survival and growth of bacteria with important functions. This approach has the unique ability to uncover higher-order combinations of bacteria that generate emergent phenotypes, information useful for development of biofertilizer, biocontrol, or probiotic consortia, as well as in the design of communities for biosynthetic compound production.

bioengineering↗

bioRxiv2018

In vitro evaluation of the decontamination effect of cold argon plasma on selected bacteria frequently encountered in small animal bite injuries

ObjectiveThe beneficial effects of cold argon plasma (CAP) on wound healing and its capacity for bacterial decontamination has recently been documented. However, despite favourable reports from experimental trials and human applications, the first in vivo studies in small animals did not prove any decontamination effect in canine bite wounds.\n\nThe present study therefore aimed to evaluate the decontamination effect of CAP in different bacteria frequently encountered in canine bite wounds in vitro.\n\nMethodsStandard strains of Escherichia (E.) coli, Staphylococcus (S.) pseudintermedius, S. aureus, Streptococcus (Sc.) canis, Pseudomonas (P.) aeruginosa and Pasteurella multocida were investigated. To evaluate the influence of the bacterial growth phase, each bacterium was incubated in nutrient broth for 3 and 8 hours, respectively, before argon plasma treatment. Three different bacterial concentrations were created per bacterium and growth phase, and each was exposed to cold plasma at a gas flow rate of 5 standard litres/minute of argon for 30 seconds, 1 minute and 2 minutes.\n\nResultsArgon treatment resulted in acceptable decontamination rates (range 98.9-99.9%) in all bacteria species in vitro; however, differences in susceptibility were detected in the different tested bacteria. Treatment time significantly (P<0.05) correlated with the decontamination rate in E. coli, Sc. canis and S. aureus, with an exposure time of 2 minutes being most effective. The initial bacterial concentration significantly (P<0.05) influenced decontamination in Pasteurella multocida and P. aeruginosa, in which treatment time was not as important. The growth phase only influenced decontamination in S. pseudintermedius.\n\nConclusionCAP exerts effective antibacterial activity against the tested bacteria strains in vitro, with species specific effects of treatment time, growth phase and concentration.

microbiology↗