A5014164653- Neurobiology and Insect Physiology Research
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Insect and Arachnid Ecology and Behavior
- Silk-based biomaterials and applications
- Animal Behavior and Reproduction
- Cell Image Analysis Techniques
- Nerve injury and regeneration
- Metabolism and Genetic Disorders
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Microfluidic and Bio-sensing Technologies
- Invertebrate Immune Response Mechanisms
- Animal Genetics and Reproduction
- Folate and B Vitamins Research
- Protein Degradation and Inhibitors
- Orbital Angular Momentum in Optics
- Click Chemistry and Applications
- Healthcare and Venom Research
- Cholinesterase and Neurodegenerative Diseases
- Plant Surface Properties and Treatments
- Inorganic Chemistry and Materials
- Plant and Biological Electrophysiology Studies
- Magnetic properties of thin films
- Blood properties and coagulation
University of Nottingham
2022-2024
MRC Laboratory of Molecular Biology
2014-2020
Janelia Research Campus
2018
Howard Hughes Medical Institute
2018
Medical Research Council
1982-2018
University of Birmingham
2008-2013
Peninsula College of Medicine and Dentistry
2013
University of Plymouth
2013
Animals exhibit innate behaviours to a variety of sensory stimuli including olfactory cues. In Drosophila, one higher centre, the lateral horn (LH), is implicated in behaviour. However, our structural and functional understanding LH scant, large part due lack sparse neurogenetic tools for this region. We generate collection split-GAL4 driver lines providing genetic access 82 cell types. use these create an anatomical neurotransmitter map link EM connectomics data. find ~30% projections...
Cytoplasmic accumulation and nuclear clearance of TDP-43 characterize familial sporadic forms amyotrophic lateral sclerosis frontotemporal lobar degeneration, suggesting that either loss or gain function, both, cause disease formation. Here we have systematically compared loss- gain-of-function Drosophila TDP-43, TAR DNA Binding Protein Homolog (TBPH), in synaptic function morphology, motor control, age-related neuronal survival. Both TBPH severely affect development result premature...
Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival, targeting, synaptic plasticity, memory cognition. We have identified a flies, Drosophila Neurotrophin (DNT1), structurally related all known neurotrophins highly conserved insects. By investigating with genetics consequences of removing DNT1 or...
Significance Cellular and subcellular structures in thick biological samples typically are visualized either by genetically encoded fluorescent proteins or antibody staining against of interest. However, both approaches have drawbacks. Fluorescent do not survive treatments for tissue preservation well, available only a few colors, often emit weak signals. Antibody stainings slow, penetrate result considerable background staining. We overcome these limitations using chemical tags that rapid,...
Abstract Efforts to map neural circuits have been galvanized by the development of genetic technologies that permit manipulation targeted sets neurons in brains freely behaving animals. The success these efforts relies on experimenter’s ability target arbitrarily small subsets for manipulation, but such specificity targeting cannot routinely be achieved using existing methods. In Drosophila melanogaster, a widely-used technique refined cell type-specific is Split GAL4 system, which augments...
Abstract Thick tissue specimens present major challenges for labeling cells and subcellular structures in a rapid reliable manner. Sutcliffe et al. present... Labeling visualizing within thick tissues, whole organs, even intact animals is key to studying biological processes. This particularly true studies of neural circuits where neurons form submicron synapses but have arbors that may span millimeters length. Traditionally, achieved by immunofluorescence; however, diffusion antibody...
Retrograde growth factors regulating synaptic plasticity at the neuromuscular junction (NMJ) in Drosophila have long been predicted but their discovery has scarce. In vertebrates, such retrograde produced by muscle include GDNF and neurotrophins (NT: NGF, BDNF, NT3 NT4). NT superfamily members identified throughout invertebrates, so far no functional vivo analysis carried out NMJ invertebrates. The family of proteins is formed DNT1, DNT2 Spätzle (Spz), with sequence, structural conservation...
Riboflavin status was measured in infants between birth and two years of age, by the erythrocyte glutathione reductase (NAD(P)H2: oxidoreductase, EC 1.6.4.2) test on finger-prick blood samples. The were living three rural Gambian villages: Keneba, Manduar Kanton Kundar; those Keneba receiving a weaning food supplement 12 months, which provided 0.15 to 0.20 mg riboflavin per day, addition their normal intake from breast milk locally available foods, 0.13 0.21 mg/day over same age range. On...
The use of genetically encoded 'self-labeling tags' with chemical fluorophore ligands enables rapid labeling specific cells in neural tissue. To improve the tagging neurons, we synthesized and evaluated new based on Cy, Janelia Fluor, Alexa ATTO dyes tested these recently improved Drosophila melanogaster transgenes. We found that tissue clearing mounting DPX substantially improves signal quality when combined non-cyanine fluorophores. compared this technique standard immunohistochemistry brain.
Abstract Microrheology with optical tweezers (MOT) is an all-optical technique that allows the user to investigate a materials’ viscoelastic properties at microscopic scales, and particularly useful for those materials feature complex microstructures, such as biological samples. MOT increasingly being employed alongside 3D imaging systems particle tracking methods generate maps showing not only how may vary between different points in sample but also single point direction. However, due...
Abstract Animals exhibit innate behaviours in response to a variety of sensory stimuli such as olfactory cues. In Drosophila , higher centre called the lateral horn (LH) is implicated behaviour. However, our knowledge structure and function LH scant, due lack sparse neurogenetic tools for this brain region. Here we generate collection split-GAL4 driver lines providing genetic access 82 cell-types. We identify neurotransmitter axo-dendritic polarity each cell-type. Using these were create an...
Abstract Genetically encoded fluorescent proteins and immunostainings are widely used to detect cellular or subcellular structures in thick biological samples. However, each approach suffers from limitations, including low signal limited spectral flexibility slow speed, poor penetration high background, respectively. Here we overcome these limitations by using transgenically expressed chemical tags for rapid, even low-background labeling of tissues. We construct a platform applicable...
Abstract New tools and techniques have enabled many key advances in our understanding of the brain. To elucidate circuit function, it is necessary to identify, record from manipulate networks connected neurons. Here we present BAcTrace ( B otulinum Ac tivated Tr acer), first fully genetically encoded, retrograde, transsynaptic labelling system. based on C. botulinum neurotoxin A, Botox, which engineered act as a Trojan horse that jumps retrogradely between neurons activate an otherwise...
The use of genetically encoded ‘self-labeling tags’ with chemical fluorophore ligands enables rapid labeling specific cells in neural tissue. To improve the tagging neurons, we synthesized and evaluated new based on Cy, Janelia Fluor, Alexa ATTO dyes tested these recently improved Drosophila melanogaster transgenes. We found that tissue clearing mounting DPX substantially improves signal quality when combined non-cyanine fluorophores. compared this technique standard immunohistochemistry brain.
The use of genetically encoded ‘self-labeling tags’ with chemical fluorophore ligands enables rapid labeling specific cells in neural tissue. To improve the tagging neurons, we synthesized and evaluated new based on Cy, Janelia Fluor, Alexa ATTO dyes tested these recently improved Drosophila melanogaster transgenes. We found that tissue clearing mounting DPX substantially improves signal quality when combined non-cyanine fluorophores. compared this technique standard immunohistochemistry brain.
Abstract Microrheology with optical tweezers (MOT) is an all-optical technique that allows for viscoelastic properties to be probed at microscopic scales, and particularly useful materials feature complex microstructures, such as biological samples. MOT increasingly being employed alongside 3D imaging systems particle tracking methods allow the mapping of materials. The inherently anisotropic nature trap strength in over a wider range frequencies, weaker axial direction will extend low...
Labeling and visualizing cells sub-cellular structures within thick tissues, whole organs even intact animals is key to studying biological processes. This particularly true for studies of neural circuits where neurons form sub-micron synapses but have arbors that may span millimeters in length. Traditionally labeling achieved by immunofluorescence; however diffusion antibody molecules (>100 kDa) slow often results uneven with very poor penetration into the centre specimens; these...