
Frank J Gunn-MooreUniversity of St Andrews · School of Biology
Frank J Gunn-Moore
BSc, PhD
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197
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Introduction
Additional affiliations
January 2007 - December 2011
January 2007 - December 2011
January 2007 - present
Publications
Publications (197)
Embryo quality assessment by optical imaging is increasing in popularity. Among available optical techniques, light sheet microscopy has emerged as a superior alternative to confocal microscopy due to its geometry, enabling faster image acquisition with reduced photodamage to the sample. However, previous assessments of photodamage induced by imagi...
Embryo quality assessment by optical imaging is increasing in popularity. Among available optical techniques, light sheet microscopy has emerged as a superior alternative to confocal microscopy due to its geometry, enabling faster image acquisition with reduced photodamage to the sample. However, previous assessments of photodamage induced by imagi...
17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) is a multifunctional mitochondrial enzyme and putative drug target for the treatment of various pathologies including Alzheimer's disease or some types of hormone-dependent cancer. In this study, a series of new benzothiazolylurea-based inhibitors were developed based on the structure-activity re...
Alzheimer’s disease (AD) is the most common neurodegenerative disease and the primary cause of disability and dependency among elderly humans worldwide. AD is thought to be a disease unique to humans although several other animals develop some aspects of AD-like pathology. Odontocetes (toothed whales) share traits with humans that suggest they may...
Willin/FRMD6 has been reported as a potential Alzheimer’s disease (AD) risk gene in a series of genome-wide association and neuroimaging studies; however, the mechanisms underlying its potential role in AD pathogenesis remain unknown. Here, we demonstrate the direct effects of Aβ on Willin/FRMD6 expression and position mitochondrial oxidative stres...
Severe brain metabolic dysfunction and amyloid-β accumulation are key hallmarks of Alzheimer's disease (AD). While astrocytes contribute to both pathologic mechanisms, the role of their mitochondria, which is essential for signaling and maintenance of these processes, has been largely understudied. The current work provides the first direct evidenc...
The FERM domain-containing protein 6 (FRMD6), also known as Willin, is an upstream regulator of Hippo signaling that has recently been shown to modulate actin cytoskeleton dynamics and mechanical phenotype of neuronal cells through ERK signaling. Physiological functions of Willin/FRMD6 in the nervous system include neuronal differentiation, myelina...
Willin/FRMD6 is part of a family of proteins with a 4.1 ezrin-radixin-moesin (FERM) domain. It has been identified as an upstream activator of the Hippo pathway and, when aberrant in its expression, is associated with human diseases and disorders. Even though Willin/FRMD6 was originally discovered in the rat sciatic nerve, most studies have focused...
Background:
Lipid dysregulation is associated with several key characteristics of Alzheimer's disease (AD), including amyloid-β and tau neuropathology, neurodegeneration, glucose hypometabolism, as well as synaptic and mitochondrial dysfunction. The β-site amyloid precursor protein cleavage enzyme 1 (BACE1) is associated with increased amyloidogen...
17β‐hydroxysteroid dehydrogenase (17β‐HSD10) is a multifunctional human enzyme with important roles both as a structural component and also as a catalyst of many metabolic pathways. This mitochondrial enzyme has important functions in the metabolism, development and aging of the neural system, where it is involved in the homeostasis of neurosteroid...
Functionally distinct synapses exhibit diverse and complex organisation at molecular and nanoscale levels. Synaptic diversity may be dependent on developmental stage, anatomical locus and the neural circuit within which synapses reside. Furthermore, astrocytes, which align with pre and post-synaptic structures to form “tripartite synapses”, can mod...
Mitochondrial dysfunction has a recognised role in the progression of Alzheimer's disease (AD) pathophysiology. Cerebral perfusion becomes increasingly inefficient throughout ageing, leading to unbalanced mitochondrial dynamics. This effect is exaggerated by amyloid β (Aβ) and phosphorylated tau, two hallmark proteins of AD pathology. A neuroprotec...
Human 17β-hydroxysteroid dehydrogenase type 10 is a multifunctional protein involved in many enzymatic and structural processes within mitochondria. This enzyme was suggested to be involved in several neurological diseases, e.g., mental retardation, Parkinson’s disease, or Alzheimer’s disease, in which it was shown to interact with the amyloid-beta...
: It has long been established that mitochondrial dysfunction in Alzheimer’s disease (AD) patients can trigger pathological changes in cell metabolism by altering metabolic enzymes such as the mitochondrial 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10), also known as amyloid-binding alcohol dehydrogenase (ABAD). We and others have shown that...
Drug delivery to the central nervous system (CNS) conferred by brain barriers is a major obstacle in the development of effective neurotherapeutics. In this review, a classification of current approaches of clinical or investigational importance for the delivery of therapeutics to the CNS is presented. This classification includes the use of formul...
Endophilin A1 (EP) is a protein enriched in synaptic terminals that has been linked to Alzheimer's disease (AD). Previous in vitro studies have shown that EP can bind to a variety of proteins, which elicit changes in synaptic transmission of neurotransmitters and spine formation. Additionally, we previously showed that EP protein levels are elevate...
We introduce a novel all-optical assay for functional studies of biological neural networks in vitro. We created a novel optogenetic construct named OptoCaMP which is a combination of a channelrhodopsin variant (CheRiff) and a red genetically encoded calcium indicator (GECI) (jRCaMP1b). It enables simultaneous optical stimulation and recording from...
Background:
The functions of the central nervous system (CNS) rely on the interaction between large populations of neurons across different areas. Therefore, to comprehend CNS functions there is a need for imaging techniques providing access to the neuronal activity of large networks of neurons with very high spatiotemporal resolution.
New method...
Scattering and absorption limit the penetration of optical fields into tissue, but wavefront correction, often used to compensate for these effects, is incompatible with wide field-of-view imaging and complex to implement. We demonstrate a new approach for increased penetration in light-sheet imaging, namely attenuation-compensation of the light fi...
Several neurodegenerative disorders including Alzheimer’s disease (AD) have been connected with deregulation of casein kinase 1 (CK1) activity. Inhibition of CK1 therefore presents a potential therapeutic strategy against such pathologies. Recently, novel class of CK1-specific inhibitors with N-(benzo[d]thiazol-2-yl)-2-phenylacetamide structural sc...
Introduction: Alzheimer's disease and diabetes mellitus are linked by epidemiology, genetics, and molecular pathogenesis. They may also be linked by the remarkable observation that insulin signaling sets the limits on longevity. In worms, flies, and mice, disrupting insulin signaling increases life span leading to speculation that caloric restricti...
Introduction:
Alzheimer's disease and diabetes mellitus are linked by epidemiology, genetics, and molecular pathogenesis. They may also be linked by the remarkable observation that insulin signaling sets the limits on longevity. In worms, flies, and mice, disrupting insulin signaling increases life span leading to speculation that caloric restrict...
Scattering and absorption limit the penetration of optical fields into tissue, but wavefront correction, often used to compensate for these effects, is incompatible with wide field-of-view imaging and complex to implement. We demonstrate a new approach for increased penetration in light-sheet imaging, namely attenuation-compensation of the light fi...
A major hallmark of Alzheimer's disease (AD) is the formation of neurotoxic aggregates composed of the amyloid-β peptide (Aβ). Aβ has been recognized to interact with numerous proteins, resulting in pathological changes to the metabolism of patients with AD. One such mitochondrial metabolic enzyme is amyloid-binding alcohol dehydrogenase (ABAD), wh...
Background:
The mitochondrial enzyme amyloid beta-binding alcohol dehydrogenase (ABAD) also known as 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) has been connected with the pathogenesis of Alzheimer's disease (AD). ABAD/ 17β-HSD10 is a binding site for the amyloid-beta peptide (Aβ) inside the mitochondrial matrix where it exacerbates Aβ t...
Alzheimer’s disease (AD) is a neurodegenerative disorder associated with an excessive accumulation of amyloid-beta peptide (Aβ). Based on the multifactorial nature of AD, preparation of multi-target-directed ligands presents a viable option to address more pathological events at one time. A novel class of asymmetrical disubstituted indolyl thiourea...
Synaptic dysfunction and dysregulation of Ca2+ are linked to neurodegenerative processes and behavioural disorders. Our understanding of the causes and factors involved in behavioural disorders and neurodegeneration, especially Alzheimer's disease (AD), a tau-related disease, is on the one hand limited and on the other hand controversial. Here, we...
Genome sequencing is now a common procedure, but prior to this, screening experiments using protein baits was one of the routinely used methods that, occasionally, allowed the identification of new gene products. One such experiment uncovered the gene product called willin/human Expanded/FRMD6. Initial characterization studies found that willin bou...
Crumbs 3 (CRB3) is a component of epithelial junctions that has been implicated in apical-basal polarity, apical identity,
apical stability, cell adhesion, and cell growth. CRB3 undergoes alternative splicing to yield two variants: CRB3a and CRB3b.
Here, we describe novel data demonstrating that as with previous studies on CRB3a, CRB3b also promote...
A major hallmark of Alzheimer's disease (AD) is the formation of toxic aggregates composed of the β-amyloid peptide (Aβ). Given that Aβ peptides are known to co-localize within mitochondria and interact with 17β-HSD10, a mitochondrial protein expressed at high levels in AD brains, we have investigated the inhibitory potential of 17β-HSD10 against A...
Fig. S1 left: Full unedited blots and gels used in Fig. 1a–c. Right: gel or blots trimmed as seen in Fig. 1. Rectangle denotes lanes/treatments shown in edited, cropped representative blots. Uncut version of acidic native gel (molecular weight markers are not used as not applicable for native gels) as seen in Fig. 1b show that the proteins do not a...
Fig. S2 Full unedited blots used in Fig. 3c and d. Rectangle denotes lanes/treatments shown in edited, cropped representative blots.
A detailed microscopic analysis of renal podocyte substructure is essential to understand and diagnose nephrotic kidney disease. Currently only time consuming electron microscopy (EM) can resolve this substructure. We used structured illumination microscopy (SIM) to examine frozen sections of renal biopsies stained with an immunofluorescence marker...
This study describes a fundamental functional difference between the two main polymorphisms of the pro-form of brain-derived neurotrophic factor (proBDNF), providing an explanation as to why these forms have such different age-related neurological outcomes. Healthy young carriers of the Met66 form (present in ∼30% Caucasians) have reduced hippocamp...
We retrospectively studied the expression of Yes-associated protein (YAP) using immunohistochemical staining in 10 cases of head and neck squamous cell carcinoma with associated perineural invasion. We find that fibroblasts in areas associated with perineural invasion show higher levels of nuclear YAP compared to fibroblasts in the stroma of normal...
We demonstrate the use of antireflection (AR) coated microparticles for the enhanced optical manipulation of cells. Specifically, we incubate CHO-K1, HL60, and NMuMG cell lines with AR-coated titania microparticles and subsequently performed drag force measurements using optical trapping. Direct comparisons were performed between native, polystyren...
Biological research requires high-speed and low-damage imaging techniques for live specimens in areas such as development study in embryos. Light sheet microscopy provides fast imaging speed whilst keeps the photo-damage and photo-blenching to minimum. Conventional sample embedding methods in light sheet imaging involves using agent such as agarose...
div class="title">Airy Beams for Light-sheet Microscopy
- Volume 21 Issue S3 - Jonathan Nylk, Zhengyi Yang, Miguel Preciado, Michael Mazilu, Tom Vettenburg, Clara Coll-Llado, David E. K. Ferrier, Tomas Cizmar, Frank. J. Gunn-Moore, Kishan Dholakia
Light sheet microscopy is a powerful approach to construct three-dimensional images of large specimens with minimal photo-damage and photo-bleaching. To date, the specimens are usually mounted in agents such as agarose, potentially restricting the development of live samples, and also highly mobile specimens need to be anaesthetized before imaging....
We demonstrate a miniaturized single beam fiber optical trapping probe based on a high numerical aperture graded index (GRIN) micro-objective lens. This enables optical trapping at a distance of 200μm from the probe tip. The fiber trapping probe is characterized experimentally using power spectral density analysis and an original approach based on...
The amyloid-β peptide (Aβ) has been associated with Alzheimer's disease (AD) for decades. The original amyloid cascade hypothesis declared that the insoluble extracellular plaques were responsible for Aβ toxicity. Later, this hypothesis has been updated and soluble intracellular Aβ forms and their effects within the cell have come into focus.Mitoch...
Benzothiazole compounds represent heterocyclic systems comprising a benzene ring fused with a thiazole ring containing nitrogen and sulphur in its structure. Besides the presence of a benzothiazole core in naturally occurring molecules, synthesized compounds containing a benzothiazole moiety in their structure proved to be a significant class of po...
EFhd2 is a calcium-binding adaptor protein that has been found to be associated with pathologically aggregated tau in the brain in Alzheimer disease and in a mouse model of frontotemporal dementia. EFhd2 has cell type–specific functions, including the modulation of intracellular calcium responses, actin dynamics, and microtubule transport. Here we...
Light-sheet imaging is rapidly gaining importance for imaging intact biological specimens. Many of the latest innovations rely on the propagation-invariant Bessel or Airy beams to form an extended light sheet to provide high resolution across a large field of view. Shaping light to realize propagation-invariant beams often relies on complex program...
Swiprosin-1/EFhd2 (EFhd2) is a cytoskeletal Ca2+ sensor protein strongly expressed in the brain. It has been shown to interact with mutant tau, which can promote neurodegeneration, but nothing is known about the physiological function of EFhd2 in the nervous system. To elucidate this question, we analyzed EFhd2-/-/lacZ reporter mice and showed that...
Light-sheet microscopy facilitates rapid, high-contrast, volumetric imaging with minimal sample exposure. However, the rapid divergence of a traditional Gaussian light sheet restricts the field of view (FOV) that provides innate subcellular resolution. We show that the Airy beam innately yields high contrast and resolution up to a tenfold larger FO...
The use of ultrashort-pulsed lasers for molecule delivery and transfection has proved to be a non-invasive and highly efficient technique for a wide range of mammalian cells. This present study investigates the effectiveness of femtosecond photoporation in plant cells, a hard-to-manipulate yet agriculturally relevant cell type, specifically suspens...
Light sheet microscopy has seen a resurgence as it facilitates rapid, high contrast, volumetric imaging with minimal sample exposure. Initially developed for imaging scattered light, this application of light sheet microscopy has largely been overlooked but provides an endogenous contrast mechanism which can complement fluorescence imaging and requ...
A prevailing problem in neuroscience is the fast and targeted delivery of DNA into selected neurons. The development of an appropriate methodology would enable the transfection of multiple genes into the same cell or different genes into different neighboring cells as well as rapid cell selective functionalization of neurons. Here, we show that opt...
A tightly-focused ultrashort pulsed laser beam incident upon a cell membrane has previously been shown to transiently increase cell membrane permeability while maintaining the viability of the cell, a technique known as photoporation. This permeability can be used to aid the passage of membrane-impermeable biologically-relevant substances such as d...
The cell selective introduction of therapeutic agents remains a challenging problem. Here we demonstrate spatially controlled cavitation instigated by laser-induced breakdown of an optically trapped single gold nanoparticle of diameter 100 nm. The energy breakdown threshold of the gold nanoparticle with a single nanosecond laser pulse at 532 nm is...