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Biology subjects

Hunter, I.

Publications and source records attributed to Hunter, I..

3 recordsLinked to original sources

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↗