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Biology subjects

Jones, J. M.

Publications and source records attributed to Jones, J. M..

7 recordsLinked to original sources

Formation of a swelling gel underlies a morphological transition in Bacillus subtilis biofilms

Microbes across species and environments form biofilms, living materials composed of cells and extracellular polymers. Biofilm-dwelling cells benefit from emergent soft matter physics that sculpts three-dimensional morphologies and osmotically absorbs nutrients. Although biofilms are modeled as viscoelastic gels, the physical origins of the phase transition underlying their conversion from groups of cells to living gels have not been systematically investigated. Here, we show that Bacillus subtilis biofilms use polymer composition to tune their physical properties and drive gel formation. Using imaging and water immersion experiments with matrix knockout strains, we demonstrate the complementary roles of two polymers in this developmental transition: hydrophilic poly-{gamma}-glutamate swells colonies by absorbing water and exopolysaccharides serve as effective cross-linkers, causing a sol-gel-like phase transition that imparts structural integrity. With matrix knockout co-culture biofilms, we independently modulate the production of each polymer and reveal a phase space of biofilm morphologies. Colonies that produce both polymers develop macroscopic wrinkles. A thin-film model predicts biofilm wrinkling from swelling-generated internal strain coupled to elasticity. The model reproduces the shape of our observed morphological phase diagram. Our results demonstrate that bacteria leverage gelation to vary their material properties and morphologies, with implications for microbial ecology and engineering living matter.

biophysics↗

Colony morphogenesis regulates sporulation dynamics in bacterial biofilms

In multicellular systems, organized phenotypic heterogeneity emerges from the interplay of processes spanning scales from molecular to population-level. Using Bacillus subtilis, we investigated feedback between the collective process of colony expansion and the distribution of spore development among individual cells, a process triggered by starvation. Biofilms are commonly studied using a strain with inhibited sporulation. Intact regulation yielded high-frequency sporulation early in biofilm growth. Biofilm composition was organized by a wave of sporulation driving biofilms toward dormancy from within. However, expansion was also maintained by non-sporulating cells in a narrow front at the external edge. Along with mathematical modeling, we also used mutants with altered biofilm morphogenesis to probe the relationship between colony expansion and sporulation. Sporulation dynamics were patterned by radial expansion, but the faster biofilms spread, the greater the separation of growth and sporulation distributions. We demonstrate essential interplay between cell behavior and the physics of collective expansion that organizes differentiation among cells.

microbiology↗

Ascending nociceptive pathways drive rapid escape and sustained avoidance in adult Drosophila

Nociception -- the detection of harmful stimuli by the nervous system -- contributes to both rapid escape and long-term avoidance behaviors. Drosophila larvae detect damaging heat, mechanical, and chemical stimuli with specialized multidendritic (md) neurons, and these cells are among the only sensory neurons that survive metamorphosis. However, it remains unknown which somatosensory neurons contribute to nociception in adult flies. In an optogenetic screen, we found that abdominal md neurons were the only somatosensory class to induce rapid escape and sustained place avoidance. Calcium imaging from abdominal md axons revealed that they are activated by thermal nociceptive stimuli (>40{degrees}C). Connectomic reconstruction showed that md axons form their strongest synaptic connections with ascending interneurons that project to the brain. Among these, we identified two classes of ascending neurons that mediate rapid escape responses and a third that supports sustained avoidance. Our findings reveal that adult Drosophila meet several core criteria commonly used to define pain: dedicated nociceptors, ascending pathways connecting peripheral sensors to integrative brain centers, and a capacity for sustained avoidance of noxious stimuli.

neuroscience↗

Distributed control circuits across a brain-and-cord connectome

Just as genomes revolutionized molecular genetics, connectomes (maps of neurons and synapses) are transforming neuroscience. To date, the only species with complete connectomes are worms1-3 and sea squirts4 (103-104 synapses). By contrast, the fruit fly is more complex (108 synaptic connections), with a brain that supports learning and spatial memory5,6 and an intricate ventral nerve cord analogous to the vertebrate spinal cord7-11. Here we report the first densely reconstructed adult fly connectome that unites the brain and ventral nerve cord, and we leverage this resource to investigate principles of neural control. We show that effector neurons (motor neurons, endocrine cells and efferent neurons targeting the viscera) are primarily influenced by sensory neurons in the same body part, forming local feedback loops. These local loops are linked by long-range circuits involving ascending and descending neurons organized into behavior-centric modules. Single ascending and descending neurons are often positioned to influence the voluntary movements of multiple body parts, together with the endocrine cells or visceral organs that support those movements. Brain regions involved in learning and navigation supervise these circuits. These results reveal an architecture that is distributed, parallelized and embodied, reminiscent of distributed control architectures in engineered systems12,13.

neuroscience↗

Chronic paternal morphine exposure increases sensitivity to morphine-derived antinociception

Parental exposure to drugs of abuse such as opioids can have profound and long-lasting effects on reward processing and drug sensitivity across generations. However, little is known about the impact of long-term paternal exposure to morphine on offspring sensitivity to morphine-derived antinociception during painful experiences. To address this question, we constructed a rat pain scale at millisecond timescales to measure mechanical nociception in a multigenerational morphine exposure paradigm. Surprisingly, while developing the pain scale, we found that von Frey hair filaments (VFHs), the most common stimuli used in pain research, are not painful to rats and morphine did not change the touch-like responses elicited by VFHs. We next deployed this novel pain scale to determine whether chronic morphine exposure in sires impacted pain sensitivity in the next generation. Offspring produced from a cross of morphine-treated sires and drug-naive dams, did not show any baseline changes in sensitivity to mechanical nociception. However, morphine-sired male progeny displayed a higher sensitivity to the antinociceptive properties of morphine, as measured by our pain scale. These findings demonstrate that long-term paternal exposure to morphine increases sensitivity to morphine-derived analgesia in the subsequent generation.

neuroscience↗

A mobile genetic element increases bacterial host fitness by manipulating development

Horizontal gene transfer is a major force in bacterial evolution. Mobile genetic elements are responsible for much of horizontal gene transfer and also carry beneficial cargo genes. Uncovering strategies used by mobile genetic elements to benefit host cells is crucial for understanding their stability and spread in populations. We describe a benefit that ICEBs1, an integrative and conjugative element of Bacillus subtilis, provides to its host cells. Activation of ICEBs1 conferred a frequency-dependent selective advantage to host cells during two different developmental processes: biofilm formation and sporulation. These benefits were due to inhibition of biofilm-associated gene expression and delayed sporulation by ICEBs1-containing cells, enabling them to exploit their neighbors and grow more prior to development. A single ICEBs1 gene, devI (formerly ydcO), was both necessary and sufficient for inhibition of development. Manipulation of host developmental programs allows ICEBs1 to increase host fitness, thereby increasing propagation of the element.

microbiology↗

3D printing of Microgel-loaded Modular LEGO-like Cages as Instructive Scaffolds for Tissue Engineering

Biomaterial scaffolds have served as the foundation of tissue engineering and regenerative medicine. However, scaffold systems are often difficult to scale in size or shape in order to fit defect-specific dimensions, and thus provide only limited spatiotemporal control of therapeutic delivery and host tissue responses. Here, a lithography-based three-dimensional (3D) printing strategy is used to fabricate a novel miniaturized modular LEGO-like cage scaffold system, which can be assembled and scaled manually with ease. Scalability is based on an intuitive concept of stacking modules, like conventional LEGO blocks, allowing for literally thousands of potential geometric configurations, and without the need for specialized equipment. Moreover, the modular hollow-cage design allows each unit to be loaded with biologic cargo of different compositions, thus enabling controllable and easy patterning of therapeutics within the material in 3D. In summary, the concept of miniaturized cage designs with such straight-forward assembly and scalability, as well as controllable loading properties, is a flexible platform that can be extended to a wide range of materials for improved biological performance. TOC3D printed LEGO-like hollow microcages can be easily assembled, adjoined, and stacked-up to suit the complexity of defect tissues; aid spatial loading of cells and biomolecules; instruct cells migration three-dimensionally; and facilitate cell invasion and neovascularization in-vivo, thus accelerating the process of tissue healing and new tissue formation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/974204v1_ufig1.gif" ALT="Figure 1"> View larger version (88K): org.highwire.dtl.DTLVardef@1a97a72org.highwire.dtl.DTLVardef@1a60fbeorg.highwire.dtl.DTLVardef@1538f13org.highwire.dtl.DTLVardef@d6345b_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗