Imperial College London

ProfessorPaulFrench

Faculty of Natural SciencesDepartment of Physics

Professor of Physics and Vice Dean (Research) - FoNS
 
 
 
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Contact

 

+44 (0)20 7594 7706paul.french Website

 
 
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Assistant

 

Ms Judith Baylis +44 (0)20 7594 7713

 
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Location

 

609Blackett LaboratorySouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

494 results found

Xavier GDS, Bellomo EA, McGinty JA, French PM, Rutter GAet al., 2013, Animal Models of GWAS-Identified Type 2 Diabetes Genes, Journal of Diabetes Research, Vol: 2013, ISSN: 2314-6753

More than 65 loci, encoding up to 500 different genes, have been implicated by genome-wide association studies (GWAS) as conferring an increased risk of developing type 2 diabetes (T2D). Whilst mouse models have in the past been central to understanding the mechanisms through which more penetrant risk genes for T2D, for example, those responsible for neonatal or maturity-onset diabetes of the young, only a few of those identified by GWAS, notably TCF7L2 and ZnT8/SLC30A8, have to date been examined in mouse models. We discuss here the animal models available for the latter genes and provide perspectives for future, higher throughput approaches towards efficiently mining the information provided by human genetics.

Journal article

Myatt SS, Kongsema M, Man CW-Y, Kelly DJ, Gomes AR, Khongkow P, Karunarathna U, Zona S, Langer JK, Dunsby CW, Coombes RC, French PM, Brosens JJ, Lam EW-Fet al., 2013, SUMOylation inhibits FOXM1 activity and delays mitotic transition, Oncogene, Vol: 33, Pages: 4316-4329, ISSN: 1476-5594

The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation is enhanced in MCF-7 breast cancer cells in response to treatment with epirubicin and mitotic inhibitors. Mutation of five consensus conjugation motifs yielded a SUMOylation-deficient mutant FOXM1. Conversely, fusion of the E2 ligase Ubc9 to FOXM1 generated an auto-SUMOylating mutant (FOXM1-Ubc9). Analysis of wild-type FOXM1 and mutants revealed that SUMOylation inhibits FOXM1 activity, promotes translocation to the cytoplasm and enhances APC/Cdh1-mediated ubiquitination and degradation. Further, expression of the SUMOylation-deficient mutant enhanced cell proliferation compared with wild-type FOXM1, whereas the FOXM1-Ubc9 fusion protein resulted in persistent cyclin B1 expression and slowed the time from mitotic entry to exit. In summary, our findings suggest that SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response.

Journal article

Kelly DJ, Alibhai D, Warren S, Kumar S, Margineanu A, Stuhmeier F, Murray EJ, Katan M, Lam EWF, Neil MAA, Dunsby C, French PMWet al., 2013, An automated flim multiwell plate reader for high content analysis

We report an automated fluorescence lifetime imaging multiwell plate reader for high content analysis, capable of subcellular mapping of protein interactions. This instrument can acquire FLIM data from 96 wells in less than 15 minutes.©2013 The Optical Society (OSA).

Conference paper

Warren S, Kimberley C, Margineanu A, Laine R, Dunsby C, Katan M, French Pet al., 2013, Flim-fret of cell signalling in chemotaxis

We demonstrate the application of Fluorescence Lifetime Imaging (FLIM) to read out Förster resonant energy transfer (FRET) based biosensors for studying the spatio-temporal dynamics of signalling pathways in cells undergoing chemotaxis. ©2013 The Optical Society (OSA).

Conference paper

Coda S, Kelly DJ, Lagarto JL, Manning HB, Patalay R, Sparks H, Thompson AJ, Warren SC, Dudhia J, Kennedy G, Nickdel MB, Talbot CB, Yamamoto K, Neil MAA, Itoh Y, McGinty J, Stamp GW, Thillainayagam AV, Dunsby C, French PMWet al., 2013, Autofluorescence lifetime imaging and metrology for medical research and clinical diagnosis

We report the development of instrumentation to utilise autofluorescence lifetime for the study and diagnosis of disease including cancer and osteoarthritis. ©2013 The Optical Society (OSA).

Conference paper

Roper JC, Yerolatsitis S, Birks TA, Mangan BJ, Dunsby C, French PMW, Knight JCet al., 2013, Minimising group index variations in a multicore endoscope fibre

We describe a multicore endoscope fibre with minimised group index variation between cores that is obtained at a V parameter of 3. Tapering the fibre input enables us to achieve single-mode propagation. © OSA 2013.

Conference paper

Nickdel MB, Lagarto JL, Kelly DJ, Manning HB, Yamamoto K, Talbot CB, Dudhia J, Dunsby C, French PM, Itoh Yet al., 2013, Detection of cartilage matrix degradation by autofluorescence lifetime, Spring Meeting of the British-Society-for-Matrix-Biology, Publisher: WILEY-BLACKWELL, Pages: A12-A13, ISSN: 0959-9673

Conference paper

Xavier GDS, Mondragon A, Mitchell R, Hodson DJ, Ferre J, Thorens B, McGinty JA, French PMW, Rutter GAet al., 2013, Defective glucose homeostasis in mice inactivated selectively for Tcf7l2 in the adult beta cell with an Ins1-controlled Cre, 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Publisher: SPRINGER, Pages: S142-S142, ISSN: 0012-186X

Conference paper

Warren SC, Margineanu A, Alibhai D, Kelly DJ, Talbot C, Alexandrov Y, Munro I, Katan M, Dunsby C, French PMWet al., 2013, Rapid Global Fitting of Large Fluorescence Lifetime Imaging Microscopy Datasets, PLOS ONE, Vol: 8, ISSN: 1932-6203

Journal article

Seidenari S, Arginelli F, Dunsby C, French PMW, Koenig K, Magnoni C, Talbot C, Ponti Get al., 2013, Multiphoton Laser Tomography and Fluorescence Lifetime Imaging of Melanoma: Morphologic Features and Quantitative Data for Sensitive and Specific Non-Invasive Diagnostics, PLOS ONE, Vol: 8, ISSN: 1932-6203

Journal article

Arginelli F, Manfredini M, Bassoli S, Dunsby C, French P, Koenig K, Magnoni C, Ponti G, Talbot C, Seidenari Set al., 2013, High resolution diagnosis of common nevi by multiphoton laser tomography and fluorescence lifetime imaging, SKIN RESEARCH AND TECHNOLOGY, Vol: 19, Pages: 194-204, ISSN: 0909-752X

Journal article

Alibhai D, Kelly DJ, Warren S, Kumar S, Margineau A, Serwa RA, Thinon E, Alexandrov Y, Murray EJ, Stuhmeier F, Tate EW, Neil MAA, Dunsby C, French PMWet al., 2013, Automated fluorescence lifetime imaging plate reader and its application to Forster resonant energy transfer readout of Gag protein aggregation, Journal of Biophotonics, Vol: 6, Pages: 398-408, ISSN: 1864-0648

Fluorescence lifetime measurements can provide quantitativereadouts of local fluorophore environment andcan be applied to biomolecular interactions via Fo¨ rsterresonant energy transfer (FRET). Fluorescence lifetimeimaging (FLIM) can therefore provide a high contentanalysis (HCA) modality to map protein-protein interactions(PPIs) with applications in drug discovery, systemsbiology and basic research. We present here an automatedmultiwell plate reader able to perform rapid unsupervisedoptically sectioned FLIM of fixed and livebiological samples and illustrate its potential to assayPPIs through application to Gag protein aggregationduring the HIV life cycle. We demonstrate both heteroFRETand homo-FRET readouts of protein aggregationand report the first quantitative evaluation of a FLIMHCA assay by generating dose response curves throughaddition of an inhibitor of Gag myristoylation. Z0 factorsexceeding 0.6 are realised for this FLIM FRET assay.Fluorescence lifetime plate map with representativeimages of high and low FRET cells and correspondingdose response plot.

Journal article

Chen L, Andrews N, Kumar S, Frankel P, McGinty J, French PMWet al., 2013, Simultaneous angular multiplexing optical projection tomography at shifted focal planes, OPTICS LETTERS, Vol: 38, Pages: 851-853, ISSN: 0146-9592

Journal article

Manfredini M, Arginelli F, Dunsby C, French P, Talbot C, Koenig K, Pellacani G, Ponti G, Seidenari Set al., 2013, High-resolution imaging of basal cell carcinoma: a comparison between multiphoton microscopy with fluorescence lifetime imaging and reflectance confocal microscopy, SKIN RESEARCH AND TECHNOLOGY, Vol: 19, Pages: E433-E443, ISSN: 0909-752X

Journal article

Manning HB, Nickdel MB, Yamamoto K, Lagarto JL, Kelly DJ, Talbot CB, Kennedy G, Dudhia J, Lever J, Dunsby C, French P, Itoh Yet al., 2013, Detection of cartilage matrix degradation by autofluorescence lifetime, MATRIX BIOLOGY, Vol: 32, Pages: 32-38, ISSN: 0945-053X

Journal article

Roper JC, Yerolatsitis S, Birks TA, Mangan BJ, Dunsby C, French PMW, Knight JCet al., 2013, Minimising group index variations in a multicore endoscope fibre, Conference on Lasers and Electro-Optics (CLEO), Publisher: IEEE, ISSN: 2160-9020

Conference paper

Martins M, Warren S, Kimberley C, Margineanu A, Peschard P, McCarthy A, Yeo M, Marshall CJ, Dunsby C, French PMW, Katan Met al., 2012, Activity of PLC epsilon contributes to chemotaxis of fibroblasts towards PDGF, JOURNAL OF CELL SCIENCE, Vol: 125, Pages: 5758-5769, ISSN: 0021-9533

Journal article

Chen L, McGinty J, Taylor HB, Bugeon L, Lamb JR, Dallman MJ, French Pet al., 2012, Improved OPT reconstructions based on the MTF and extension to FLIM-OPT

We demonstrate the improved reconstruction of OPT datasets by incorporating the measured MTF in the reconstruction process. We also extend OPT to FLIM-OPT and demonstrate its use for imaging live zebrafish embryos displaying autofluorescence. © 2012 OSA.

Conference paper

Laine R, Stuckey DW, Manning H, Warren SC, Kennedy G, Carling D, Dunsby C, Sardini A, French PMWet al., 2012, Fluorescence Lifetime Readouts of Troponin-C-Based Calcium FRET Sensors: A Quantitative Comparison of CFP and mTFP1 as Donor Fluorophores, PLOS ONE, Vol: 7, ISSN: 1932-6203

Journal article

Seidenari S, Arginelli F, Dunsby C, French P, Koenig K, Magnoni C, Manfredini M, Talbot C, Ponti Get al., 2012, Multiphoton laser tomography and fluorescence lifetime imaging of basal cell carcinoma: morphologic features for non-invasive diagnostics, EXPERIMENTAL DERMATOLOGY, Vol: 21, Pages: 831-836, ISSN: 0906-6705

Journal article

Xavier GDS, Mondragon A, Sun G, Chen L, McGinty JA, French PM, Rutter GAet al., 2012, Abnormal glucose tolerance and insulin secretion in pancreas-specific Tcf7l2-null mice, DIABETOLOGIA, Vol: 55, Pages: 2667-2676, ISSN: 0012-186X

Journal article

Patalay R, Talbot C, Alexandrov Y, Lenz MO, Kumar S, Warren S, Munro I, Neil MAA, Koenig K, French PMW, Chu A, Stamp GWH, Dunsby Cet al., 2012, Multiphoton Multispectral Fluorescence Lifetime Tomography for the Evaluation of Basal Cell Carcinomas, PLOS One, Vol: 7, ISSN: 1932-6203

We present the first detailed study using multispectral multiphoton fluorescence lifetime imaging to differentiate basal cell carcinoma cells (BCCs) from normal keratinocytes. Images were acquired from 19 freshly excised BCCs and 27 samples of normal skin (in & ex vivo). Features from fluorescence lifetime images were used to discriminate BCCs with a sensitivity/specificity of 79%/93% respectively. A mosaic of BCC fluorescence lifetime images covering >1 mm2 is also presented, demonstrating the potential for tumour margin delineation.Using 10,462 manually segmented cells from the image data, we quantify the cellular morphology and spectroscopic differences between BCCs and normal skin for the first time. Statistically significant increases were found in the fluorescence lifetimes of cells from BCCs in all spectral channels, ranging from 19.9% (425–515 nm spectral emission) to 39.8% (620–655 nm emission). A discriminant analysis based diagnostic algorithm allowed the fraction of cells classified as malignant to be calculated for each patient. This yielded a receiver operator characteristic area under the curve for the detection of BCC of 0.83.We have used both morphological and spectroscopic parameters to discriminate BCC from normal skin, and provide a comprehensive base for how this technique could be used for BCC assessment in clinical practice.

Journal article

Brown AC, Oddos S, Dobbie IM, Alakoskela JM, Parton RM, Eissmann P, Neil MA, Dunsby C, French PM, Davis I, Davis DMet al., 2012, Correction: Remodelling of Cortical Actin Where Lytic Granules Dock at Natural Killer Cell Immune Synapses Revealed by Super-Resolution Microscopy., PLoS Biol, Vol: 10

[This corrects the article on p. e1001152 in vol. 9.].

Journal article

Patalay R, Chu A, Dunsby C, Talbot C, Konig K, French P, Alexandrov Yet al., 2012, A noninvasive imaging study of skin using two photon microscopy of cellular autofluorescence, 70th Annual Meeting of the American-Academy-of-Dermatology (AAD), Publisher: MOSBY-ELSEVIER, Pages: AB83-AB83, ISSN: 0190-9622

Conference paper

Chen L, McGinty J, Taylor HB, Bugeon L, Lamb JR, Dallman MJ, French PMWet al., 2012, Incorporation of an experimentally determined MTF for spatial frequency filtering and deconvolution during optical projection tomography reconstruction, OPTICS EXPRESS, Vol: 20, Pages: 7323-7337, ISSN: 1094-4087

Journal article

Thompson AJ, Coda S, Sorensen MB, Kennedy G, Patalay R, Waitong-Bramming U, De Beule PAA, Neil MAA, Andersson-Engels S, Bendsoe N, French PMW, Svanberg K, Dunsby Cet al., 2012, In vivo measurements of diffuse reflectance and time-resolved autofluorescence emission spectra of basal cell carcinomas, JOURNAL OF BIOPHOTONICS, Vol: 5, Pages: 240-254, ISSN: 1864-063X

Journal article

Sardini A, Stuckey DW, McGinty J, Laine R, Soloviev VY, Arridge SR, Wells DJ, French PMW, Hajnal JVet al., 2012, In Vivo Investigation of Calpain Activity by Lifetime Imaging of Genetically Encoded FRET Sensors, BIOPHYSICAL JOURNAL, Vol: 102, Pages: 159A-159A, ISSN: 0006-3495

Journal article

Esseling M, Kemper B, Antkowiak M, Stevenson DJ, Chaudet L, Neil MAA, French PW, von Bally G, Dholakia K, Denz Cet al., 2012, Multimodal biophotonic workstation for live cell analysis, JOURNAL OF BIOPHOTONICS, Vol: 5, Pages: 9-13, ISSN: 1864-063X

Journal article

Antkowiak M, Torres-Mapa ML, McGinty J, Chahine M, Bugeon L, Rose A, Finn A, Moleirinho S, Okuse K, Dallman M, French P, Harding SE, Reynolds P, Gunn-Moore F, Dholakia Ket al., 2012, Towards gene therapy based on femtosecond optical transfection, BIOPHOTONICS: PHOTONIC SOLUTIONS FOR BETTER HEALTH CARE III, Vol: 8427, ISSN: 0277-786X

Journal article

Seidenari S, Arginelli F, Bassoli S, Cautela J, French PMW, Guanti M, Guardoli D, K├Ânig K, Talbot C, Dunsby Cet al., 2012, Multiphoton laser microscopy and fluorescence lifetime imaging for the evaluation of the skin., Dermatol Res Pract, Vol: 2012

Multiphoton laser microscopy is a new, non-invasive technique providing access to the skin at a cellular and subcellular level, which is based both on autofluorescence and fluorescence lifetime imaging. Whereas the former considers fluorescence intensity emitted by epidermal and dermal fluorophores and by the extra-cellular matrix, fluorescence lifetime imaging (FLIM), is generated by the fluorescence decay rate. This innovative technique can be applied to the study of living skin, cell cultures and ex vivo samples. Although still limited to the clinical research field, the development of multiphoton laser microscopy is thought to become suitable for a practical application in the next few years: in this paper, we performed an accurate review of the studies published so far, considering the possible fields of application of this imaging method and providing high quality images acquired in the Department of Dermatology of the University of Modena.

Journal article

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