A mutualistic model bacterium is lethal to non-symbiotic hosts via the type VI secretion system.

What makes a bacterium pathogenic? Since the early days of germ theory, researchers have categorized bacteria as pathogens or non-pathogens, those that cause harm and those that do not, but this binary view is not always accurate. is an exclusive mutualistic symbiont found within the light organs of Hawaiian bobtail squid. This symbiotic interaction requires to utilize a range of behaviors and produce molecules that are often associated with pathogenicity.

Effect of Voltage-Gated K Channel Inhibition by 4-aminopyridine in Spinal Cord Injury Recovery in Zebrafish.

Spinal cord injury (SCI) affects between 250,000 to 500,000 individuals annually. After the initial injury, a delayed secondary cascade of cellular responses occurs causing progressive degeneration and permanent disability. One part of this secondary process is disturbance of ionic homeostasis.

Differential Roles of Diet on Development and Spinal Cord Regeneration in Larval Zebrafish.

The zebrafish is a powerful model organism for studying development and regeneration. However, there is a lack of a standardized reference diet for developmental and regeneration experiments. Most studies evaluate the rate of growth, survival, and fecundity.

Non-invasive single cell aptasensing in live cells and animals.

We report a genetically encoded aptamer biosensor platform for non-invasive measurement of drug distribution in cells and animals. We combined the high specificity of aptamer molecular recognition with the easy-to-detect properties of fluorescent proteins. We generated six encoded aptasensors, showcasing the platform versatility.

Effects of age on the response to spinal cord injury: optimizing the larval zebrafish model.

Zebrafish are an increasingly popular model to study regeneration after spinal cord injury (SCI). The transparency of larval zebrafish makes them ideal to study cellular processes in real time. Standardized approaches, including age at the time of injury, are not readily available making comparisons of the results with other models challenging.

Aquatic Freshwater Vertebrate Models of Epilepsy Pathology: Past Discoveries and Future Directions for Therapeutic Discovery.

Epilepsy is an international public health concern that greatly affects patients' health and lifestyle. About 30% of patients do not respond to available therapies, making new research models important for further drug discovery. Aquatic vertebrates present a promising avenue for improved seizure drug screening and discovery.

Targeted cell ablation in zebrafish using optogenetic transcriptional control.

Cell ablation is a powerful method for elucidating the contributions of individual cell populations to embryonic development and tissue regeneration. Targeted cell loss in whole organisms has been typically achieved through expression of a cytotoxic or prodrug-activating gene product in the cell type of interest. This approach depends on the availability of tissue-specific promoters, and it does not allow further spatial selectivity within the promoter-defined region(s).

Correcting glucose-6-phosphate dehydrogenase deficiency with a small-molecule activator.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L).

Mutant SOD1 protein increases Nav1.3 channel excitability.

Amyotrophic lateral sclerosis (ALS) is a lethal paralytic disease caused by the degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. Mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) are present in ~20% of familial ALS and ~2% of all ALS cases. The most common SOD1 gene mutation in North America is a missense mutation substituting valine for alanine (A4V).

Bioreactive Tethers.

Ion channel complexes are challenging to study by traditional biochemical methods due to their membranous lipid environment and large size. Bioreactive tethers are specialized chemical probes that have been used in electrophysiological experiments to provide unique insight into ion channel structure and function. Because bioreactive tethers are small molecular probes, they can be used to manipulate ion channel function in heterologous expression systems, native cells and animal models.

Thinking big with small molecules.

Synthetic chemistry has enabled scientists to explore the frontiers of cell biology, limited only by the laws of chemical bonding and reactivity. As we investigate biological questions of increasing complexity, new chemical technologies can provide systems-level views of cellular function. Here we discuss some of the molecular probes that illustrate this shift from a "one compound, one gene" paradigm to a more integrated approach to cell biology.

Calmodulation meta-analysis: predicting calmodulin binding via canonical motif clustering.

The calcium-binding protein calmodulin (CaM) directly binds to membrane transport proteins to modulate their function in response to changes in intracellular calcium concentrations. Because CaM recognizes and binds to a wide variety of target sequences, identifying CaM-binding sites is difficult, requiring intensive sequence gazing and extensive biochemical analysis. Here, we describe a straightforward computational script that rapidly identifies canonical CaM-binding motifs within an amino acid sequence.

Structural insights into neuronal K+ channel-calmodulin complexes.

Calmodulin (CaM) is a ubiquitous intracellular calcium sensor that directly binds to and modulates a wide variety of ion channels. Despite the large repository of high-resolution structures of CaM bound to peptide fragments derived from ion channels, there is no structural information about CaM bound to a fully folded ion channel at the plasma membrane. To determine the location of CaM docked to a functioning KCNQ K(+) channel, we developed an intracellular tethered blocker approach to measure distances between CaM residues and the ion-conducting pathway.

Xenopus laevis oocytes infected with multi-drug-resistant bacteria: implications for electrical recordings.

The Xenopus laevis oocyte has been the workhorse for the investigation of ion transport proteins. These large cells have spawned a multitude of novel techniques that are unfathomable in mammalian cells, yet the fickleness of the oocyte has driven many researchers to use other membrane protein expression systems. Here, we show that some colonies of Xenopus laevis are infected with three multi-drug-resistant bacteria: Pseudomonas fluorescens, Pseudomonas putida, and Stenotrophomonas maltophilia.

Discovery of a novel activator of KCNQ1-KCNE1 K channel complexes.

KCNQ1 voltage-gated K(+) channels (Kv7.1) associate with the family of five KCNE peptides to form complexes with diverse gating properties and pharmacological sensitivities. The varied gating properties of the different KCNQ1-KCNE complexes enables the same K(+) channel to function in both excitable and non excitable tissues.

Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a cytokine with potential therapeutic value against cancers because of its selective cytotoxicity to many transformed, but not normal, cells. The "decoy receptors" TRAIL-R3 (TR3) and TRAIL-R4 (TR4) were believed to negatively regulate TRAIL-induced cytotoxicity by competing for ligand binding with TRAIL-R1 (TR1) and TRAIL-R2 (TR2). Here, we show that inhibition of TRAIL-induced apoptosis by TR4 critically depends on its association with TR2 via the NH(2)-terminal preligand assembly domain overlapping the first partial cysteine-rich domain of both receptors.