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Biology subjects

Hunter, I.

Publications and source records attributed to Hunter, I..

5 recordsLinked to original sources

Renewable Self-Folding Origami Constructed from Bioengineered Bacterial Cellulose

This work presents the first genetically engineered cellulose actuator where the structural basis for actuation is directly encoded in the producing organisms DNA. By modifying Komagataeibacter rhaeticus to secrete BslA protein and treating with NaOH, we create surface-activated bacterial cellulose that exhibits water contact angles 2.4x greater than and water retention 8.2 x less than unmodified cellulose. Layering this hydrophobic BslA-activated cellulose with untreated bacterial cellulose produces a biofabricated actuator driven by differential strain during dehydration. The actuation follows the Timoshenko bilayer beam equation adapted for hydrogels and can be fabricated either by shaping mature pellicles or through direct growth in 3D-printed autoclavable molds. We demonstrate two applications with a self-folding bacterial cellulose origami crane and a biomimetic bacterial cellulose gripper capable of supporting more than 360 times its own weight. This approach represents a significant advance in sustainable soft robotics through the creation of fully renewable, biodegradable, and genetically programmable actuators.

synthetic biology↗

Balance of Activity during a Critical Period Tunes a Developing Network

Developing neural circuits are influenced by activity and are especially sensitive to changes in activity during critical periods (CPs) of development. Changes occurring during a CP often become locked-in so that they affect the mature network. Indeed, several neurodevelopmental disorders have been linked to excessive activity during such periods. It is, therefore, important to identify those aspects of neural circuit development that are influenced by neural activity during a CP. In this study, we take advantage of the genetic tractability of Drosophila to show that activity perturbation during an embryonic CP permanently alters properties of the locomotor circuit. Specific changes we identify include increased synchronicity of motoneuron activity, and greater strengthening of excitatory over inhibitory synaptic drive to motoneurons. These changes are sufficient to reduce network robustness, evidenced by increased sensitivity to induced seizure. We also show that we can rescue these changes when increased activity is mitigated by inhibition provided by mechanosensory neurons. Similarly, we demonstrate a dose-dependent relationship between inhibition experienced during the CP, and the extent to which it is possible to rescue the hyperexcitable phenotype characteristic of the parabss mutation. This suggests that developing circuits must be exposed to a properly balanced sum of excitation and inhibition during the CP to achieve normal mature network function. Our results, therefore, provide novel insight into how activity during a CP shapes specific elements of a circuit, and how activity during this period is integrated to tune neural circuits to the environment in which they will likely function.

neuroscience↗

A Theoretical Framework for Relating Natural Movement to Length and Quality of Life in Human and Non-human Animals

Natural movement is clearly related to health, however, it is also highly complex and difficult to measure. Most attempts to measure it focus on functional movements in humans, and while this a valid and popular approach, assays focussed on particular movements cannot capture the range of natural movement that occurs outside them. It is also difficult to use current techniques to compare movement across animal species. Interspecies comparison may be useful for identifying conserved biomechanical and/ or computational principles of movement that could inform human and veterinary medicine, plus several other fields of research. It is therefore important that research develops a system for quantifying movement in freely moving animals in natural environments and relating it to length and quality of life (LQOL). The present text proposes a novel theoretical framework for doing so, based on movement ability (MA). MA is comprised of three major variables - Movement Quality, Movement Complexity, and Movement Quantity - that may represent the most important components of movement as it relates to LQOL. A constrained version of the framework is validated in Drosophila, which suggests that MA may indeed represent a useful new paradigm for understanding the relationship between movement and length and quality of life.

systems biology↗

The Drosophila orthologue of the primary ciliary dyskinesia-associated gene, DNAAF3, is required for axonemal dynein assembly

Ciliary motility is powered by a suite of highly conserved axoneme-specific dynein motor complexes. In humans the impairment of these motors through mutation results in the disease, Primary Ciliary Dyskinesia (PCD). Studies in Drosophila have helped to validate several PCD genes whose products are required for cytoplasmic pre-assembly of axonemal dynein motors. Here we report the characterisation of the Drosophila homologue of the less known assembly factor, DNAAF3. This gene, CG17669 (Dnaaf3), is expressed exclusively in developing mechanosensory chordotonal (Ch) neurons and spermatocytes, the only two Drosophila cell types bearing motile cilia/flagella. Mutation of Dnaaf3 results in larvae that are deaf and adults that are uncoordinated, indicating defective Ch neuron function. The mutant Ch neuron cilia of the antenna specifically lack dynein arms, while Ca imaging in larvae reveals a complete loss of Ch neuron response to vibration stimulus, confirming that mechanotransduction relies on ciliary dynein motors. Mutant males are infertile with immotile sperm whose flagella lack dynein arms and show axoneme disruption. Analysis of proteomic changes suggest a reduction in heavy chains of all axonemal dynein forms, consistent with an impairment of dynein pre-assembly. SUMMARY STATEMENTDNAAF3 function as a dynein assembly factor for motile cilia is conserved in Drosophila.

cell biology↗

The role of insulators and transcription in 3D chromatin organisation of flies

The DNA in many organisms, including humans, is shown to be organised in topologically associating domains (TADs). In Drosophila, several architectural proteins are enriched at TAD borders, but it is still unclear whether these proteins play a functional role in the formation and maintenance of TADs. Here, we show that depletion of BEAF-32, Cp190, Chro and Dref leads to changes in TAD organisation and chromatin loops. Their depletion predominantly affects TAD borders located in heterochromatin, while TAD borders located in euchromatin are resilient to these mutants. Furthermore, transcriptomic data has revealed hundreds of genes displaying differential expression in these mutants and showed that the majority of differentially expressed genes are located within reorganised TADs. Our work identifies a novel and functional role for architectural proteins at TAD borders in Drosophila and a link between TAD reorganisation and subsequent changes in gene expression.

genomics↗