A5041209830- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
- Axon Guidance and Neuronal Signaling
- Neurobiology and Insect Physiology Research
- Cellular transport and secretion
- Skin and Cellular Biology Research
- Developmental Biology and Gene Regulation
- Silk-based biomaterials and applications
- Genetics, Aging, and Longevity in Model Organisms
- Ubiquitin and proteasome pathways
- Invertebrate Immune Response Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Autophagy in Disease and Therapy
- Cardiomyopathy and Myosin Studies
- Plant Reproductive Biology
- Protein Degradation and Inhibitors
- Nerve injury and regeneration
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Animal Genetics and Reproduction
- Angiogenesis and VEGF in Cancer
- Proteins in Food Systems
- Photosynthetic Processes and Mechanisms
- Coenzyme Q10 studies and effects
- Studies on Chitinases and Chitosanases
- Lysosomal Storage Disorders Research
University of Liverpool
2016-2025
University of Manchester
2005-2013
Wellcome Centre for Cell-Matrix Research
2005-2012
Johannes Gutenberg University Mainz
2003
University of Cambridge
1996-2000
The correct outgrowth of axons is essential for the development and regeneration nervous systems. Axon growth primarily driven by microtubules. Key regulators microtubules in this context are spectraplakins, a family evolutionarily conserved actin-microtubule linkers. Loss function mouse spectraplakin ACF7 or its close Drosophila homolog Short stop/Shot similarly cause severe axon shortening microtubule disorganization. How spectraplakins perform these functions not known. Here we show that...
Axons are crucial for transmitting neurochemical signals. As organisms age, the ability of neurons to maintain their axons declines; hence, aged more susceptible damage or dysfunction. Understanding how aging causes axonal vulnerability is developing strategies enhance overall resilience and prevent neuronal deterioration during in age-related neurodegenerative diseases. Increasing levels reactive oxygen species (ROS) oxidative stress - a hallmark Despite this association, causal...
We have cloned and characterised a member of the High Mobility Group superfamily genes from Drosophila, Sox70D, which is closely related to mammalian testis determining gene SRY. Sox70D corresponds dominant wing mutation Dichaete. Homozygous deletions recessive lethal Dichaete alleles variable embryonic segmentation phenotype. expressed in early embryos dynamic pattern reminiscent gap pair-rule required for appropriate expression primary even skipped, hairy runt. The molecular nature its...
Spectraplakins are large actin-microtubule linker molecules implicated in various processes, including gastrulation, wound healing, skin blistering and neuronal degeneration. Expression data for the mammalian spectraplakin ACF7 genetic analyses of Drosophila Short stop (Shot) suggest an important role during neurogenesis. Using three parallel culture systems we demonstrate that, like Shot, is essential axon extension describe, first time, their subcellular functions axonal growth. Firstly,...
The regulation of growth cone actin dynamics is a critical aspect axonal control. Among the proteins that are directly involved in dynamics, nucleation factors play pivotal role by promoting formation novel filaments. However, essential developing neurons have so far not been clearly identified. Here, we show expression data, and use true loss-of-function analysis targeted activated constructs to demonstrate Drosophila formin DAAM plays morphogenesis. In agreement with this finding, dDAAM...
Abstract The formation of neuronal networks, during development and regeneration, requires outgrowth axons along reproducible paths toward their appropriate postsynaptic target cells. Axonal extension occurs at growth cones (GCs) the tips axons. GC advance navigation activity cytoskeletal comprising filamentous actin (F‐actin) in lamellipodia filopodia as well dynamic microtubules (MTs) emanating from bundles axonal core. molecular mechanisms governing these two cross‐talk, response to...
The mechanisms regulating synapse numbers during development and ageing are essential for normal brain function closely linked to disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in numbers, thus unravelling an important cellular requirement Tau. In this context, find that displays a strong functional overlap with microtubule-binding spectraplakins, establishing new links between two different neurodegenerative factors....
Directed axonal growth depends on correct coordination of the actin and microtubule cytoskeleton in cone. However, despite relatively large number proteins implicated actin-microtubule crosstalk, mechanisms whereby polymerization is coupled to stabilization advancement peripheral cone remained largely unclear. Here, we identified formin Dishevelled-associated activator morphogenesis (DAAM) as a novel factor playing role concerted regulation remodeling Drosophilamelanogaster primary neurons....
Natural ageing is accompanied by a decline in motor, sensory, and cognitive functions, all impacting quality of life. Ageing also the predominant risk factor for many neurodegenerative diseases, including Parkinson’s disease Alzheimer’s disease. We need to therefore gain better understanding cellular physiological processes underlying age-related neuronal decay. However, gaining this slow process due large amount time required age mammalian or vertebrate animal models. Here, we introduce new...
Peroxisomes are essential organelles involved in critical metabolic processes animals such as fatty acid oxidation, ether phospholipid production and reactive oxygen species detoxification. We have generated transgenic Drosophila melanogaster models expressing fluorescent reporters for the selective autophagy of peroxisomes, a process known pexophagy. show that these colocalized with peroxisomal marker they can reflect pexophagy induction by iron chelation inhibition depletion core protein...
Cortical collapse factors affect microtubule (MT) dynamics at the plasma membrane. They play important roles in neurons, as suggested by inhibition of axon growth and regeneration through ARF activator Efa6 C. elegans, neurodevelopmental disorders linked to mammalian kinesin Kif21A. How cortical influence is little understood. Here we studied them, focussing on function Drosophila experimentally genetically amenable fly neurons. First, show that can inhibit MTs directly without interacting...
The formation and maintenance of microtubules requires their polymerisation, but little is known about how this polymerisation regulated in cells. Focussing on the essential microtubule bundles axons Drosophila Xenopus neurons, we show that plus-end scaffold Eb1, polymerase XMAP215/Msps lattice-binder Tau co-operate interdependently to promote bundle organisation during axon development maintenance. Eb1 each other's localisation at polymerising plus-ends. outcompetes Eb1-binding along...
F-actin networks are important structural determinants of cell shape and morphogenesis. They regulated through a number actin-binding proteins. The function many these proteins is well understood, but very little known about how they cooperate integrate their activities in cellular contexts. Here, we have focussed on the roles actin regulators controlling filopodial dynamics. Filopodia needle-shaped, actin-driven protrusions with characteristic features that conserved amongst vertebrates...
Axonal branching allows a neuron to connect several targets, increasing neuronal circuit complexity. While axonal is well described, the mechanisms that control it remain largely unknown. We find in Drosophila CNS branches develop through process of excessive growth followed by pruning. In vivo high-resolution live imaging developing brains as loss and gain function experiments show activation Epidermal Growth Factor Receptor (EGFR) necessary for branch dynamics final pattern. Live also...
The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo also contribute to brain circuits. Whether molecular mechanisms regulating these signals modified fit more complex processes is unclear. We investigated the role in Drosophila higher-order circuits identified differences cellular Robo/Slit function. First, we find that signaling by regulated Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane...
The phenomenon of pioneer neurons has been known for almost a century, but so far we have little insights into mechanisms and molecules involved. Here, study the formation Drosophila intersegmental motor nerve (ISN). We show that aCC/RP2 U grow together at leading front ISN. Nevertheless, are pioneers, followers, because only effectively influence growth also this depends on neural cell adhesion molecule homolog FasciclinII. First, ablation stronger impact ISN than ablation. Second, strong...