A5102868065- Photoreceptor and optogenetics research
- Retinal Development and Disorders
- Circadian rhythm and melatonin
- LGBTQ Health, Identity, and Policy
- Gender, Feminism, and Media
- Neuroscience and Neural Engineering
- Neurobiology and Insect Physiology Research
- African Sexualities and LGBTQ+ Issues
- Media Studies and Communication
- Face Recognition and Perception
- Neuroinflammation and Neurodegeneration Mechanisms
- Sexuality, Behavior, and Technology
- Receptor Mechanisms and Signaling
- Visual perception and processing mechanisms
- melanin and skin pigmentation
- Neural dynamics and brain function
- Media, Gender, and Advertising
- Planarian Biology and Electrostimulation
- Gender Politics and Representation
- Political Philosophy and Ethics
- Neuroscience and Neuropharmacology Research
- Animal Behavior and Reproduction
- Multicultural Socio-Legal Studies
- Spatial Cognition and Navigation
- Spatial Neglect and Hemispheric Dysfunction
University of Manchester
2018-2025
University of Oxford
2014-2021
Manchester Academic Health Science Centre
2021
John Radcliffe Hospital
2016
University of York
2012-2014
Queensland University of Technology
2010
Animal opsins are light-sensitive G-protein-coupled receptors (GPCRs) that enable optogenetic control over the major heterotrimeric G-protein signaling pathways in animal cells. As such, have potential applications both biomedical research and therapy. Selecting opsin with best balance of activity selectivity for a given application requires knowing their ability to couple full range relevant Gα subunits. We present GsX assay, set tools based on chimeric Gs subunits transduce coupling...
Vertebrate retinas share a basic blueprint comprising 5 neuronal classes arranged according to common wiring diagram. Yet, vision is aligned with species differences in behavior and ecology, raising the question of how evolution acts on this circuit adjust its computational characteristics. We address that problem by comparing thalamic visual code retinal cell composition closely related occupying different niches: Rhabdomys pumilio, which are day-active murid rodents, nocturnal laboratory...
Animals detect light using opsin photopigments. Xenopsin, a recently classified subtype of opsin, challenges our views on and photoreceptor evolution. Originally thought to belong the Gαi-coupled ciliary opsins, xenopsins are now understood have diverged from opsins in pre-bilaterian times, but little is known about cells that deploy these proteins, or if they form photopigment drive phototransduction. We characterized xenopsin flatworm, Maritigrella crozieri, found it expressed eyes larva,...
Abstract Gnat −/− , Cnga3 Opn4 triple knockout (TKO) mice lack essential components of phototransduction signalling pathways present in rods, cones and photosensitive retinal ganglion cells (pRGCs) are therefore expected to all sensitivity light. However, a number studies have shown that light responses persist these mice. In this study we use multielectrode array (MEA) recordings light-induced c-fos expression further characterise the TKO retina. Small, but robust electroretinogram type...
There is no consensus on the best inhibitory optogenetic tool. Since Gi/o signalling a native mechanism of neuronal inhibition, we asked whether Lamprey Parapinopsin ("Lamplight"), Gi/o-coupled bistable animal opsin, could be used for silencing. We show that short (405 nm) and long (525 wavelength pulses repeatedly switch Lamplight between stable active inactive states, respectively, combining these wavelengths can to achieve intermediate levels activity. These properties applied produce...
Highlights•ReaChR in bipolar cells restores high-quality visual responses rd1 mice•ReaChR stimulus-response characteristics show equivalent diversity to WT•rd1 system can parse features into multiple output channels•Remodeling after photoreceptor loss has a limited impact on functional capacitySummaryPhotoreceptor degeneration sufficient produce severe often spares the inner retina. This raises hope for vision restoration treatments using optogenetics or electrical stimulation, which...
Abstract Measuring vision in rodents is a critical step for understanding vision, improving models of human disease, and developing therapies. Established behavioural tests perceptual such as the visual water task, rely on learning. The learning process, while effective sighted animals, can be laborious stressful animals with impaired requiring long periods training. Current that do not require training are based sub-conscious, reflex responses (e.g. optokinetic nystagmus) don’t involvement...
Human opsin-based photopigments have great potential as light-sensitisers, but their requirement for phototransduction cascade-specific second messenger proteins may restrict functionality in non-native cell types. In this study, eight chimeric human opsins were generated consisting of a backbone either rhodopsin (RHO) or long-wavelength-sensitive (LWS) opsin and intracellular domains from Gq/11-coupled melanopsin. Rhodopsin/melanopsin coupled to both Gi Gq/11 pathways. Greater substitution...
Melanopsin is a blue light-sensitive opsin photopigment involved in range of non-image forming behaviours, including circadian photoentrainment and the pupil light response. Many naturally occurring genetic variants exist within human melanopsin gene (OPN4), yet it remains unclear how these affect protein function downstream physiological responses to light. Here, we have used bioinformatic analysis vitro expression systems determine functional phenotypes missense OPN4 variants. From 1242...
Melanopsin is an opsin photopigment and light-activated G-protein-coupled receptor; it expressed in photoreceptive retinal ganglion cells (mRGCs) can be employed as optogenetic tool. Mammalian melanopsins signal via Gq/11 Gi/o/t heterotrimeric G proteins, but aspects of the mRGC light response appear incompatible with either mode signalling. We use live-cell reporter assays HEK293T to show that from mice humans also Gs. subsequently this signalling substantially divergent between species....
Melanopsin (OPN4) is an opsin photopigment expressed within intrinsically photosensitive retinal ganglion cells (ipRGCs) that mediate non-image forming (NIF) responses to light. Two single-nucleotide polymorphisms (SNPs) in human melanopsin (hOPN4), Pro10Leu and Thr394Ile, have recently been associated with abnormal NIF light, including seasonal affective disorder. It has suggested these behavioural changes are due altered signalling. However, there currently no direct evidence support this....
An animal's temporal niche - the time of day at which it is active known to drive a variety adaptations in visual system. These include variations topography, spectral sensitivity and density retinal photoreceptors, changes eye's gross anatomy transmission characteristics. We have characterised murid rodent Rhabdomys pumilio (the four-striped grass mouse), same family as (nocturnal) mice rats but exhibits strong diurnal niche. As common species, R. lens acts long-pass filter, providing...
Animal opsins are light activated G-protein-coupled receptors, capable of optogenetic control G-protein signalling for research or therapeutic applications. offer excellent photosensitivity, but their temporal resolution can be limited by long photoresponse duration when expressed outside native cellular environment. Here, we explore methods addressing this limitation a prototypical animal opsin (human rod opsin) in HEK293T cells. We find that the application canonical rhodopsin kinase...
Light has a profound impact on mammalian physiology and behavior. Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin, rendering them sensitive to light, are involved in both image-forming vision non-image forming responses light such as circadian photo-entrainment pupillary reflex. Following outer photoreceptor degeneration, death of rod cone photoreceptors results global re-modeling remnant neural retina. Although ipRGCs can continue signaling...
The viral gene delivery of optogenetic actuators to the surviving inner retina has been proposed as a strategy for restoring vision in advanced retinal degeneration. We investigated safety ectopic expression human rod opsin (hRHO), and two channelrhodopsins (enhanced sensitivity CoChR-3M red-shifted ReaChR) by ON bipolar cells mouse retina. Adult Grm6Cre mice were bred be retinally degenerate or non-retinally (homozygous heterozygous rd1Pde6b mutation, respectively) intravitreally injected...
Abstract How does evolution act on neuronal populations to match computational characteristics functional demands? We address this problem by comparing visual code and retinal cell composition in closely related murid species with different behaviours. Rhabdomys pumilio are diurnal have substantially thicker inner retina larger thalamus than nocturnal Mus musculus . High-density electrophysiological recordings of response features the dorsal lateral geniculate nucleus (dLGN) reveals that...
ABSTRACT Optogenetic therapy is a promising vision restoration method where light sensitive opsins are introduced to the surviving inner retina following photoreceptor degeneration. The cell type targeted for opsin expression will likely influence quality of restored vision. However, like-for-like pre-clinical comparison visual responses evoked equivalent in two major targets, ON bipolar (ON BCs) or retinal ganglion cells (RGCs), absent. We address this deficit by comparing stimulus-response...
ABSTRACT Degenerative retinal disorders leading to irreversible photoreceptor death are a common cause of blindness. Optogenetic gene therapy aims restore vision in affected individuals by introducing light sensitive opsins into the surviving neurons inner retina. While up until now main focus optogenetic has been on terminally blind individuals, treating at stages where residual native is present could have several advantages. Yet, it still unknown how and would interact if same time. Using...
The allocation of spatial attention results in enhanced perception at attended locations the cost unattended locations. While functional MRI (fMRI) studies have shown that cortical representations visual can display negative BOLD responses, this ‘suppression’ remains poorly understood. We sought to characterise suppression expressed retinotopic asking following questions. At what stages hierarchy is expressed? What task- and stimulus contrast- dependence suppression? Participants viewed...