Imperial College London

DrJamesMcGinty

Faculty of Natural SciencesDepartment of Physics

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 7719james.mcginty

 
 
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Location

 

621Blackett LaboratorySouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

91 results found

Davis SPX, Kumar S, Alexandrov Y, Bhargava A, da Silva Xavier G, Rutter GA, Frankel P, Sahai E, Flaxman S, French PMW, McGinty Jet al., 2019, Convolutional neural networks for reconstruction of undersampled optical projection tomography data applied to in vivo imaging of zebrafish., J Biophotonics

Optical projection tomography (OPT) is a 3D mesoscopic imaging modality that can utilize absorption or fluorescence contrast. 3D images can be rapidly reconstructed from tomographic data sets sampled with sufficient numbers of projection angles using the Radon transform, as is typically implemented with optically cleared samples of the mm-to-cm scale. For in vivo imaging, considerations of phototoxicity and the need to maintain animals under anesthesia typically preclude the acquisition of OPT data at a sufficient number of angles to avoid artifacts in the reconstructed images. For sparse samples, this can be addressed with iterative algorithms to reconstruct 3D images from undersampled OPT data, but the data processing times present a significant challenge for studies imaging multiple animals. We show here that convolutional neural networks (CNN) can be used in place of iterative algorithms to remove artifacts - reducing processing time for an undersampled in vivo zebrafish dataset from 77 to 15 minutes. We also show that using CNN produces reconstructions of equivalent quality to CS with 40% fewer projections. We further show that diverse training data classes, for example ex vivo mouse tissue data, can be used for CNN-based reconstructions of OPT data of other species including live zebrafish. This article is protected by copyright. All rights reserved.

Journal article

Chen L, Li G, Tang L, Zhang M, Liu L, Liu A, McGinty J, Ruan Set al., 2019, Hyperspectral scanning laser optical tomography, Journal of Biophotonics, Vol: 12, ISSN: 1864-063X

In order to study physical relationships within tissue volumes or even organism-level systems, the spatial distribution of multiple fluorescent markers needs to be resolved efficiently in three dimensions. Here, rather than acquiring discrete spectral images sequentially using multiple emission filters, a hyperspectral scanning laser optical tomography system is developed to obtain hyperspectral volumetric data sets with 2-nm spectral resolution of optically transparent mesoscopic (millimeter-centimeter) specimens. This is achieved by acquiring a series of point-scanning hyperspectral extended depth of field images at different angles and subsequently tomographically reconstructing the 3D intensity distribution for each wavelength. This technique is demonstrated to provide robust measurements via the comparison of spectral and intensity profiles of fluorescent bead phantoms. Due to its enhanced spectral resolving ability, this technique is also demonstrated to resolve largely overlapping fluorophores, as demonstrated by the 3D fluorescence hyperspectral reconstruction of a dual-labeled mouse thymus gland sample and the ability to distinguish tumorous and normal tissues of an unlabeled mouse intestine sample.

Journal article

French P, Davis S, Wisniewski L, Kumar S, Correia T, Arridge S, Frankel P, McGinty Jet al., 2018, Slice-illuminated optical projection tomography, Optics Letters, Vol: 43, Pages: 5555-5558, ISSN: 0146-9592

To improve the imaging performance of optical projection tomography (OPT) in live samples, we have explored a parallelized implementation of semi-confocal line illumination and detection to discriminate against scattered photons. Slice-illuminated OPT (sl-OPT) improves reconstruction quality in scattering samples by reducing interpixel crosstalk at the cost of increased acquisition time. For in vivo imaging, this can be ameliorated through the use of compressed sensing on angularly undersampled OPT data sets. Here, we demonstrate sl-OPT applied to 3D imaging of bead phantoms and live adult zebrafish.

Journal article

Wisniewski L, Davis S, Lockwood N, Mcginty J, French P, Frankel Pet al., 2018, A role for p130Cas in venous sprouting and lymphangiogenesis in the zebrafish, 5th Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology, Publisher: OXFORD UNIV PRESS, Pages: S90-S90, ISSN: 0008-6363

Conference paper

Rutter GA, Haythorne EA, Georgiadou E, Xavier GDS, Pullen TJ, Rizzuto R, Martinez-Sanchez A, McGinty JA, French PMet al., 2018, Pancreatic beta cell-selective deletion of the mitochondrial calcium uniporter (MCU) impairs glucose-stimulated insulin secretion in vitro but not in vivo, Publisher: WILEY, Pages: 42-42, ISSN: 0742-3071

Conference paper

Chen L, Li G, Li Y, Li Y, Zhu H, Tang L, French P, McGinty J, Ruan Set al., 2017, UbasM: An effective balanced optical clearing method for intact biomedical imaging, Scientific Reports, Vol: 7, ISSN: 2045-2322

Optical clearing methods can facilitate deep optical imaging in biological tissue by reducing light scattering and this has enabled accurate three-dimensional signal visualization and quantification of complex biological structures. Unfortunately, existing optical clearing approaches present a compromise between maximizing clearing capability, the preservation of fluorescent protein emission and membrane integrity and the speed of sample processing – with the latter typically requiring weeks for cm scale tissue samples. To address this challenge, we present a new, convenient, aqueous optical clearing agent, termed UbasM: Urea-Based Amino-Sugar Mixture, that rapidly renders fixed tissue samples highly transparent and reliably preserves emission from fluorescent proteins and lipophilic dyes in membrane integrity preserved tissues. UbasM is simple, inexpensive, reproducible and compatible with all labeling methods that we have encountered. It can enable convenient, volumetric imaging of tissue up to the scale of whole adult mouse organs and should be useful for a wide range of light microscopy and tomography techniques applied to biomedical research, especially the study on organism-level systems biology at multiple levels.

Journal article

Watson, Andrews N, Davis S, Bugeon L, Dallman M, McGinty Jet al., 2017, OPTiM: optical projection tomography integrated microscope using open-source hardware and software, PLOS One, Vol: 12, ISSN: 1932-6203

We describe the implementation of an OPT plate to perform optical projection tomography (OPT) on a commercial wide-field inverted microscope, using our open-source hardware and software. The OPT plate includes a tilt adjustment for alignment and a stepper motor for sample rotation as required by standard projection tomography. Depending on magnification requirements, three methods of performing OPT are detailed using this adaptor plate: a conventional direct OPT method requiring only the addition of a limiting aperture behind the objective lens; an external optical-relay method allowing conventional OPT to be performed at magnifications >4x; a remote focal scanning and region-of-interest method for improved spatial resolution OPT (up to ~1.6 μm). All three methods use the microscope’s existing incoherent light source (i.e. arc-lamp) and all of its inherent functionality is maintained for day-to-day use. OPT acquisitions are performed on in vivo zebrafish embryos to demonstrate the implementations’ viability.

Journal article

Van de Pette M, Abbas A, Feytout A, McNamara G, Bruno L, To WK, Dimond A, Sardini A, Webster Z, McGinty J, Paul EJ, Ungless MA, French PMW, Withers DJ, Uren A, Ferguson-Smith AC, Merkenschlager M, John RM, Fisher AGet al., 2017, Visualizing changes in Cdkn1c expression links early life adversity to imprint mis-regulation in adults, Cell Reports, Vol: 31, Pages: 1090-1099, ISSN: 2211-1247

Imprinted genes are regulated according to parental origin and can influence embryonic growth and metabolism and confer disease susceptibility.Here we designed sensitive allele-specific reporters to non-invasively monitor imprinted Cdkn1cexpression in mice and showed that expression was modulated by environmental factors encounteredin utero.Acute exposure to chromatin modifyingdrugs resulted in de-repression of paternally inherited (silent) Cdkn1calleles in embryos that was temporary and resolved after birth.In contrast, deprivation of maternal dietary proteinin uteroprovoked permanent de-repression of imprinted Cdkn1cexpression that was sustained into adulthood and occurred through a folate-dependent mechanism of DNA methylation loss.Given the function of imprinted genes in regulating behavior and metabolic processes in adults, these results establish imprinting deregulation as a credible mechanism linking early life adversity to later-life outcomes.Furthermore,Cdkn1c-luciferasemice offer non-invasivetools to identify factors that disrupt epigenetic processes and strategies to limit their long-term impact.

Journal article

French PMW, Görlitz F, Kelly D, Warren S, Alibhai D, West L, Kumar S, Alexandrov Y, Munro I, McGinty J, Talbot C, Serwa R, Thinon E, Da Paola V, Murray EJ, Stuhmeier F, Neil M, Tate E, Dunsby Cet al., 2017, Open source high content analysis utilizing automated fluorescence lifetime imaging microscopy, Jove-Journal of Visualized Experiments, Vol: 119, ISSN: 1940-087X

We present an open source high content analysis instrument utilizing automated fluorescence lifetime imaging (FLIM) for assaying protein interactions using Förster resonance energy transfer (FRET) based readouts of fixed or live cells in multiwell plates. This provides a means to screen for cell signaling processes read out using intramolecular FRET biosensors or intermolecular FRET of protein interactions such as oligomerization or heterodimerization, which can be used to identify binding partners. We describe herethe functionality of this automated multiwell plate FLIM instrumentation and present exemplar data from our studies of HIV Gag protein oligomerization and a time course of a FRET biosensor in live cells. A detailed description of the practical implementation is then provided with reference to a list of hardware components and a description of the open source data acquisition software written in μ Manager. The application of FLIMfit, an open source MATLAB-based client for the OMERO platform, to analyze arrays of multiwell plate FLIM data is also presented. The protocols for imaging fixed and live cells are outlined and a demonstration of an automated multiwell plate FLIM experiment using cells expressing fluorescent protein-based FRET constructs is presented. This is complemented by a walk-through of the data analysis for this specific FLIM FRET data set.

Journal article

Andrews N, Davis S, Hay C, Kumar S, Ramel M-C, Bugeon L, McGinty J, Dallman MJ, French PMWet al., 2017, Functional imaging of live Zebrafish using fluorescence lifetime optical projection tomography, Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XV, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 0277-786X

Conference paper

Chandaria VV, McGinty J, Nowlan NC, 2016, Characterising the effects of in vitro mechanical stimulation on morphogenesis of developing limb explants, Journal of Biomechanics, Vol: 49, Pages: 3635-3642, ISSN: 1873-2380

Mechanical forces due to fetal movements play an important role in joint shape morphogenesis, and abnormalities of the joints relating to abnormal fetal movements can have long-term health implications. While mechanical stimulation during development has been shown to be important for joint shape, the relationship between the quantity of mechanical stimulation and the growth and shape change of developing cartilage has not been quantified. In this study, we culture embryonic chick limb explants in vitro in order to reveal how the magnitude of applied movement affects key aspects of the developing joint shape. We hypothesise that joint shape is affected by movement magnitude in a dose-dependent manner, and that a movement regime most representative of physiological fetal movements will promote characteristics of normal shape development. Chick hindlimbs harvested at seven days of incubation were cultured for six days, under either static conditions or one of three different dynamic movement regimes, then assessed for joint shape, cell survival and proliferation. We demonstrate that a physiological magnitude of movement in vitro promotes the most normal progression of joint morphogenesis, and that either under-stimulation or over-stimulation has detrimental effects. Providing insight into the optimal level of mechanical stimulation for cartilage growth and morphogenesis is pertinent to gaining a greater understanding of the etiology of conditions such as developmental dysplasia of the hip, and is also valuable for cartilage tissue engineering.

Journal article

Rutter GA, Semplici F, Mondragon A, Macintyre B, Madeyski-Bengston K, Persson-Kry A, Ramne A, Marley A, McGinty J, French P, Soedling H, Yokosuka R, Gaiten J, Lang J, Migrenne-Li S, Philippe E, Herrera PL, Magnan C, da Silva Xavier Get al., 2016, Cell type-specific deletion in mice reveals roles for PAS kinase in insulin and glucagon production, Diabetologia, Vol: 59, Pages: 1938-1947, ISSN: 1432-0428

Background and Aims. Per-Arnt-Sim domain containing kinase (PASK) is a nutrient regulated protein kinase previously implicated in the control of insulin gene expression and glucagon secretion. Here, we explore the roles of the kinase in the control of islet hormone release by generating mice deleted selectively for the Pask gene in pancreatic beta or alpha cells. Methods. Floxed alleles of Pask were produced by homologous recombination and animals bred with mice bearing beta (Ins1Cre, PaskBKO), or alpha (PPG-Cre; PaskAKO) cell selective Cre recombinase alleles. Glucose homeostasis and hormone secretion in vivo and in vitro, gene expression, and islet cell mass, were measured using standard techniques.Results. Ins1Cre-based recombination led to efficient beta cell targeted deletion of Pask. Beta cell mass was reduced by 36.5% (p<0.05) compared to controls in PaskBKO mice, as well as in global null Pask mice (38%, p<0.05). PaskBKO mice displayed normal body weight and fasting glycemia, but slightly impaired glucose tolerance, and beta cell proliferation, after maintenance on a high fat diet. Whilst glucose tolerance was unaffected in PaskAKO mice, glucose infusion rates were increased, and glucagon secretion tended to be lower, during hypoglycemic clamps. Though alpha cell mass was increased (21.9%, p<0.05), glucagon release at low glucose was impaired (p<0.05) in PaskAKO islets. Conclusions. The present findings demonstrate cell autonomous roles for PASK in the control of pancreatic endocrine hormone secretion. Differencesbetween the glycemic phenotype of global versus cell type specific null mice suggest important roles for tissue interactions in the control of glycemia by the kinase.

Journal article

Kumar S, Lockward N, Ramel M-C, Correia T, Ellis M, Alexandrov Y, Andrews N, Patel R, Bugeon L, Dallman M, Brandner S, Arridge S, Katan M, McGinty J, Frankel P, French PMWet al., 2016, Quantitative in vivo optical tomography of cancer progression & vasculature development in adult zebrafish, Oncotarget, Vol: 7, Pages: 43939-43948, ISSN: 1949-2553

We describe a novel approach to study tumour progression and vasculature development in vivo via global 3-D fluorescence imaging of live non-pigmented adult zebrafish utilising angularly multiplexed optical projection tomography with compressive sensing (CS-OPT). This “mesoscopic” imaging method bridges a gap between established ~μm resolution 3-D fluorescence microscopy techniques and ~mm-resolved whole body planar imaging and diffuse tomography. Implementing angular multiplexing with CS-OPT, we demonstrate the in vivo global imaging of an inducible fluorescently labelled genetic model of liver cancer in adult non-pigmented zebrafish that also present fluorescently labelled vasculature. In this disease model, addition of a chemical inducer (doxycycline) drives expression of eGFP tagged oncogenic K-RASV12 in the liver of immune competent animals. We show that our novel in vivo global imaging methodology enables non-invasive quantitative imaging of the development of tumour and vasculature throughout the progression of the disease, which we have validated against established methods of pathology including immunohistochemistry. We have also demonstrated its potential for longitudinal imaging through a study of vascular development in the same zebrafish from early embryo to adulthood. We believe that this instrument, together with its associated analysis and data management tools, constitute a new platform for in vivo cancer studies and drug discovery in zebrafish disease models.

Journal article

French PMW, andrews N, dallman M, ramel MC, kumar S, alexandrov Y, kelly D, warren S, kerry L, bugeon L, Lockwood N, Frolov Aet al., 2016, Visualising apoptosis in live zebrafish using fluorescence lifetime imaging with optical projection tomography to map FRET biosensor activity in space and time, Journal of Biophotonics, Vol: 9, Pages: 414-424, ISSN: 1864-0648

Fluorescence lifetime imaging (FLIM) combined with optical projection tomography (OPT) has the potential to map Förster resonant energy transfer (FRET) readouts in space and time in intact transparent or near transparent live organisms such as zebrafish larvae, thereby providing a means to visualise cell signalling processes in their physiological context. Here the first application of FLIM OPT to read out biological function in live transgenic zebrafish larvae using a genetically expressed FRET biosensor is reported. Apoptosis, or programmed cell death, is mapped in 3-D by imaging the activity of a FRET biosensor that is cleaved by Caspase 3, which is a key effector of apoptosis. Although apoptosis is a naturally occurring process during development, it can also be triggered in a variety of ways, including through gamma irradiation. FLIM OPT is shown here to enable apoptosis to be monitored over time, in live zebrafish larvae via changes in Caspase 3 activation following gamma irradiation at 24 hours post fertilisation. Significant apoptosis was observed at 3.5 hours post irradiation, predominantly in the head region.

Journal article

Watson TJ, Andrews N, Harry E, Bugeon L, Dallman MJ, French PMW, McGinty Jet al., 2016, Remote focal scanning and sub-volume optical projection tomography

© OSA 2016. We present a platform for sub-volume optical projection tomography utilising an electrically tunable lens and tracking technology. Applied to 3D fluorescent bead phantoms and zebrafish embryos, we demonstrate an improvement in resolution and light collection efficiency with respect to conventional optical projection tomography.

Conference paper

Watson TJ, Andrews N, Harry E, Bugeon L, Dallman MJ, French PMW, McGinty Jet al., 2016, Remote focal scanning and sub-volume optical projection tomography

© OSA 2016. We present a platform for sub-volume optical projection tomography utilising an electrically tunable lens and tracking technology. Applied to 3D fluorescent bead phantoms and zebrafish embryos, we demonstrate an improvement in resolution and light collection efficiency with respect to conventional optical projection tomography.

Conference paper

Andrews N, Ramel MC, Kumar S, Alexandrov Y, Kelly DJ, Warren SC, Kerry L, Lockwood N, Frolov A, Frankel P, Bugeon L, McGinty J, Dallman MJ, French PMWet al., 2016, Fluorescence lifetime optical projection tomography and FRET applied to visualizing apoptosis in live zebrafish larvae

© OSA 2016. We present the application of FLIM-OPT to read out biological function in live transgenic zebrafish larvae using a genetically expressed cleavable FRET biosensor for Caspase-3 as an indicator of gamma radiation induced apoptosis.

Conference paper

McGinty J, French P, Frankel P, 2016, Novel 3D imaging platform tracks cancer progression in vivo, Biochemist, Vol: 38, Pages: 12-15, ISSN: 0954-982X

© 2016 Biochemical Society. Optical imaging underpins biomedical research in many respects and recent decades have seen spectacular advances, particularly in fluorescence imaging where genetic engineering approaches to labelling have been combined with new light sources, detectors and data analysis techniques to provide capabilities like super-resolution beyond the diffraction limit, exquisite spectroscopic contrast for molecular readouts and high-speed image capture for in vivo and high-throughput applications. However, the main impact of such advanced instrumentation and data analysis has been to provide unprecedented quantitative 2D and 3D information concerning samples compatible with microscopy where volumes of less than 1 mm3 are typically imaged in a single 'acquisition'. The ability to view and measure cellular processes and signalling pathways in live cells has been a significant advance for biomedical research and drug discovery. However, for conventional microscope-based assays and experiments, the samples typically comprise thin layers of cells that are not experiencing the same signals that they would in a 3D tissue context and any findings may not directly translate to live organisms. It is desirable to study disease processes in live intact organisms that can provide appropriate physiological complexity. For cancer studies, recent research from our group shows that optical tomography can be used to directly monitor in vivo changes in tumour growth and vascular development in a zebrafish cancer model over time. This technique not only improves the value of the collected data, but if used on a wider scale should result in a reduction in the number of animals used in biomedical research.

Journal article

Correia T, Lockwood N, Kumar S, Yin J, Ramel M-C, Andrews N, Katan M, Bugeon L, Dallman MJ, McGinty J, Frankel P, French PMW, Arridge Set al., 2015, Accelerated optical projection tomography applied to in vivo imaging of zebrafish, PLOS One, Vol: 10, ISSN: 1932-6203

Optical projection tomography (OPT) provides a non-invasive 3-D imaging modality that can be applied to longitudinal studies of live disease models, including in zebrafish. Current limitations include the requirement of a minimum number of angular projections for reconstruction of reasonable OPT images using filtered back projection (FBP), which is typically several hundred, leading to acquisition times of several minutes. It is highly desirable to decrease the number of required angular projections to decrease both the total acquisition time and the light dose to the sample. This is particularly important to enable longitudinal studies, which involve measurements of the same fish at different time points. In this work, we demonstrate that the use of an iterative algorithm to reconstruct sparsely sampled OPT data sets can provide useful 3-D images with 50 or fewer projections, thereby significantly decreasing the minimum acquisition time and light dose while maintaining image quality. A transgenic zebrafish embryo with fluorescent labelling of the vasculature was imaged to acquire densely sampled (800 projections) and under-sampled data sets of transmitted and fluorescence projection images. The under-sampled OPT data sets were reconstructed using an iterative total variation-based image reconstruction algorithm and compared against FBP reconstructions of the densely sampled data sets. To illustrate the potential for quantitative analysis following rapid OPT data acquisition, a Hessian-based method was applied to automatically segment the reconstructed images to select the vasculature network. Results showed that 3-D images of the zebrafish embryo and its vasculature of sufficient visual quality for quantitative analysis can be reconstructed using the iterative algorithm from only 32 projections—achieving up to 28 times improvement in imaging speed and leading to total acquisition times of a few seconds.

Journal article

Chen L, Alexandrov Y, Kumar S, Andrews N, Dallman MJ, French PMW, McGinty Jet al., 2015, Mesoscopic in vivo 3-D tracking of sparse cell populations using angular multiplexed optical projection tomography, BIOMEDICAL OPTICS EXPRESS, Vol: 6, Pages: 1253-1261, ISSN: 2156-7085

Journal article

Sayers S, Kantor C, Pullen TJ, Nguyen-Tu MS, Hodson DJ, McGinty J, Lingling C, French P, Ibberson M, Thorens Bet al., 2015, Preserved insulin secretion despite impaired glucose signalling after pancreatic beta cell selective deletion of the tumour suppressor LKB1, Publisher: WILEY-BLACKWELL, Pages: 13-13, ISSN: 0742-3071

Conference paper

Mitchell RK, Mondragon A, Chen L, Mcginty JA, French PM, Ferrer J, Thorens B, Hodson DJ, Rutter GA, Xavier GDSet al., 2015, Selective disruption of Tcf7l2 in the pancreatic beta cell impairs secretory function and lowers beta cell mass, HUMAN MOLECULAR GENETICS, Vol: 24, Pages: 1390-1399, ISSN: 0964-6906

Journal article

Kelly DJ, Warren SC, Alibhai D, Kumar S, Alexandrov Y, Munro I, Margineanu A, McCormack J, Welsh NJ, Serwa RA, Thinon E, Kongsema M, McGinty J, Talbot C, Murray EJ, Stuhmeier F, Neil MAA, Tate EW, Braga VMM, Lam EW-F, Dunsby C, French PMWet al., 2015, Automated multiwell fluorescence lifetime imaging for Forster resonance energy transfer assays and high content analysis, ANALYTICAL METHODS, Vol: 7, Pages: 4071-4089, ISSN: 1759-9660

Journal article

McGinty J, Chen L, Kumar S, Alexandrov Y, Andrews N, Kelly D, Dallman MJ, French PMWet al., 2015, Techniques to improve the spatial and temporal resolution in optical projection tomography: Remote focal scanning and time-lapse cell tracking

© OSA 2015. Optical projection tomography is a 3-D imaging approach applicable to transparent samples and model organisms like zebrafish embryos. We present methods to improve the spatial resolution and realize 3-D cell tracking in OPT.

Conference paper

Kone M, Sun G, Ibberson M, Martinez-Sanchez A, Sayers S, Marie-Sophie N-T, Kantor C, Swisa A, Dor Y, Gorman T, Ferrer J, Thorens B, Reimann F, Gribble F, McGinty JA, Chen L, French PM, Birzele F, Hildebrandt T, Uphues I, Rutter GAet al., 2014, LKB1 and AMPK differentially regulate pancreatic beta-cell identity, Faseb Journal, Vol: 28, Pages: 4972-4985, ISSN: 1530-6860

Fully differentiated pancreatic b cellsare essential for normal glucose homeostasis in mammals.Dedifferentiation of these cells has been suggestedto occur in type 2 diabetes, impairing insulinproduction. Since chronic fuel excess (“glucotoxicity”)is implicated in this process, we sought here to identifythe potential roles in b-cell identity of the tumor suppressorliver kinase B1 (LKB1/STK11) and the downstreamfuel-sensitive kinase, AMP-activated proteinkinase (AMPK). Highly b-cell-restricted deletion ofeach kinase in mice, using an Ins1-controlled Cre, wastherefore followed by physiological, morphometric,and massive parallel sequencing analysis. Loss of LKB1strikingly (2.0–12-fold, E<0.01) increased the expressionof subsets of hepatic (Alb, Iyd, Elovl2) and neuronal(Nptx2, Dlgap2, Cartpt, Pdyn) genes, enhancing glutamatesignaling. These changes were partially recapitulatedby the loss of AMPK, which also up-regulated b-cell“disallowed” genes (Slc16a1, Ldha, Mgst1, Pdgfra) 1.8- to3.4-fold (E<0.01). Correspondingly, targeted promoterswere enriched for neuronal (Zfp206; P51.3310233)and hypoxia-regulated (HIF1; P52.5310216) transcriptionfactors. In summary, LKB1 and AMPK, through onlypartly overlapping mechanisms, maintain b-cell identityby suppressing alternate pathways leading to neuronal,hepatic, and other characteristics. Selective targetingof these enzymes may provide a new approach tomaintaining b-cell function in some forms of diabetes.—Kone,M., Pullen, T. J., Sun, G., Ibberson, M.,Martinez-Sanchez, A., Sayers, S., Nguyen-Tu, M.-S.,Kantor, C., Swisa, A., Dor, Y., Gorman, T., Ferrer, J.,Thorens, B., Reimann, F., Gribble, F., McGinty, J. A.,Chen, L., French, P. M., Birzele, F., Hildebrandt, T.,Uphues, I., Rutter, G. A. LKB1 and AMPK differentiallyregulate pancreatic b-cell identity.

Journal article

Chen L, Kumar S, Kelly D, Andrews N, Dallman MJ, French PMW, McGinty Jet al., 2014, Remote focal scanning optical projection tomography with an electrically tunable lens, BIOMEDICAL OPTICS EXPRESS, Vol: 5, Pages: 3367-3375, ISSN: 2156-7085

Journal article

Xavier GDS, Mondragon A, Mitchell R, Hodson D, Ferrer J, Thorens B, Chen L, Mcginty J, French P, Rutter GAet al., 2014, Defective glucose homeostasis in mice inactivated selectively for Tcf7l2 in the adult beta cell with an Ins1-controlled Cre, 50th EASD Annual Meeting, Publisher: Springer Verlag (Germany), Pages: S151-S151, ISSN: 1432-0428

Conference paper

Watson TJ, Andrews N, Harry E, Bugeon L, Dallman MJ, French PMW, McGinty Jet al., 2014, Remote focal scanning and sub-volume optical projection tomography

© OSA 2016. We present a platform for sub-volume optical projection tomography utilising an electrically tunable lens and tracking technology. Applied to 3D fluorescent bead phantoms and zebrafish embryos, we demonstrate an improvement in resolution and light collection efficiency with respect to conventional optical projection tomography.

Conference paper

Kumar S, Lockwood N, Ramel MC, Correia T, Ellis M, Alexandrov Y, Andrews N, Patel R, Bugeon L, Dallman MJ, Brandner S, Arridge S, Katan M, McGinty J, Frankel P, French PMWet al., 2014, In vivo multiplexed OPT and FLIM OPT of an adult zebrafish cancer disease model

© OSA 2016. We report angular multiplexed OPT and FLIM OPT applied to in vivo imaging of cancer and FRET biosensors in adult zebrafish. Multiple-spectral 3-D datasets of entire adult zebrafish can be acquired in 3 minutes.

Conference paper

Marcu L, French PMW, Elson DS, 2014, Preface, ISBN: 9781439861677

© 2015 by Taylor & Francis Group, LLC. Wide-field time-gated fluorescence lifetime imaging (FLIM) essentially entails illuminating a sample with an ultrashort pulse of excitation radiation and sampling the resulting time varying fluorescence “image” following excitation by acquiring a series of gated fluorescence intensity images recorded at different relative delays with respect to the excitation pulse. This is represented schematically in Figure 8.1. In the simplest case, a map of the mean fluorescence decay times across the field of view is obtained. If the sampling of the fluorescence decay profiles is appropriately detailed, then the entire fluorescence decay profile for each image pixel can be acquired, and the resulting data set can be fitted to complex temporal decay models. For example, a double exponential decay model is frequently used to analyze data from Förster resonant energy transfer (FRET) experiments. The acquisition of time-gated fluorescence intensity images requires a 2-D detector, normally a charge-coupled device (CCD) camera, and some kind of fast “shutter” able to sample fluorescence decay profiles on subnanosecond timescales. Such a “shutter” function cannot be provided by mechanical means or yet by electronic circuitry and is typically provided by optical image intensifiers whose gain can be modulated by varying the applied voltage.

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