ESRIC welcomes researchers from a range of disciplines and institutes, below are some examples of a few of these projects as well as the list of publications that have come out of the facility since 2013. We love to hear how you are getting on and you can fill us in at this quick 2 questions survey here or enter any new publications at your ppms account page here.

Polarity signalling in central nervous system myelin

Professor Charles ffrench-Constant 
Dr. Andrew Jarjour (PDRA)
Centre for Regenerative Medicine, University of Edinburgh

This project used the multicolour and 3-Dimensional super-resolution technique, STED, to visualise polarity signalling in oligodendroglia at the regions flanking the nodes of ranvier. Proper polarization of the myelin sheath at these paranodal regions is essential for axo-glial adhesion and the resultant organization of the axon into the distinct molecular domains required for rapid impulse conduction. Understanding the mechanisms involved in polarizing the myelin sheath requires that the myelin sheath be imaged in fine detail, which as seen in the image, STED can provide. This work has significant influence on our understanding of how CNS myelin forms and the demyelination that is seen in patients with multiple sclerosis. 

Andrew Jarjour image STED scaled down

Image of a nerve cell (red) with myelin wrapped around in a spiral (green) shows the level of detail in STED (left) compared to standard imaging (right)

Ion channels in sperm cells and their association with impaired fertility

Dr Sean Brown
School of Science, Engineering and Technology, Abertay University

This project aims to investigate the expression and intracellular localisation of ion channels inside human sperm as it has been found that abnormal channel phenotypes are associated with impaired fertilisation. In particular the knocking out of certain genes that relate to impaired fertility can drastically change calcium channel arrangement along the tail. This project is using single molecule localisation microscopy techniques to quantify the molecular organisation on the nanometer scale over 3 dimensions. 

Sean BrownCalcium channel localisation inside a human sperm cell imaged on the ESRIC Olympus TIRF system, right hand image shows zoom.

Cellular communication and diabetes

Dr Colin Rickman
Dr. Deirdre Kavanagh (PDRA)
Institute of Biological Chemistry, Bioengineering and Biophysics, Heriot-Watt University
Funded by MRC and Wellcome Trust

Using single molecule localisation microscopy such as PALM and STORM this project aims to understand the plasma membrane organisation of tSNARE proteins underlying insulin secretion in β-cells under normal physiological conditions and how this is altered in Type 2 related hyperglycemia. Previous work combined these techniques with Fluorescence Cross Correlation Spectroscopy to study SNARE protein interactions in neuronal cells.

DeeFigure panel from: A molecular toggle after exocytosis sequesters the presynaptic ​syntaxin1a molecules involved in prior vesicle fusion, Nature Communications 2014.

3D Printing of Tumours

Dr Nick Leslie (PI)
Miguel Hermida (PhD)
Institute of Biological Chemistry, Bioengineering and Biophysics, Heriot-Watt University
Funded by Anonymous Trust

This project involves the development of a 3D printing strategy, which uses common biocompatible hydrogels to create multilineage tumour-like structures. These are visualised in ESRIC using live-cell 3D confocal imaging with the aim to study the tumour microenvironment and provide novel highly-reproducible models for preclinical drug testing.

Miguel crop3D printed construct in RGD-Alginate showing U87MG-EYFP glioblastoma cells, WI-38 Cerulean fibroblasts and activated MM-6 mCherry macrophages, 24h after printing. Imaged using the SP5 Confocal laser scanning microscope.

Distribution of pathogen associated molecular patterns on the Candida albicans cell surface

Prof. A. Brown (PI)
Dr Judith Bain (PDRA)
School of Medicine, Medical Sciences and Nutrition, University of Aberdeen
Funded by MRC

This project investigates the cell surface arrangement of pathogen associated molecular patterns (PAMPS), including β-glucan, on the wall of the fungal pathogen, Candida albicans. In this collaboration, Structured Illumination Microscopy (SIM) is used to visualise alterations in PAMP exposure in response to altered host factors.

Judithβ-glucan on the C. albicans cell surface, visualised by Fc-Dectin-1 using the SIM system

Analysis of human lung tissue and bacterial labelling compounds

Dr Kev Dhaliwal (PI)
Dr Tushar Choudhary (PDRA) 
Centre for Inflammation Research, University of Edinburgh
Funded by EPSRC

This collaborative project between Heriot-Watt University and Edinburgh University investigates the properties of markers for lung diseases, which forms part of the Proteus project; developing a tool for next-generation diagnostic testing of lung disease. Fluorescence Lifetime Imaging Microscopy (FLIM) is used to study the fluorescent properties of these markers.

Tushar cropConfocal images of fluorescently-labelled bacteria and the corresponding image showing the Fluorescence Lifetimes of each bacteria in a false colour scale

Investigating granular dynamics in renin-producing primary cells

Dr John Mullins (PI)
Dr Charlotte Buckley (PDRA) 
BHF Centre for Cardiovascular Science, University of Edinburgh
Funded by British Heart Foundation

The transport and dynamics of renin-producing granules inside primary juxtaglomerular cells has been investigated in a collaborative project between Universities. This research has been possible using TIRF microscopy and photoactivation techniques at ESRIC allowing live-cell tracking and quantification of calcium dynamics.

Combined StacksGranules (left panel) inside a renin-producing (right panel, green) juxtaglomerular cell imaged in live-cell conditions using the Ollympus IX81 TIRF system.

Super-Resolution imaging of postsynaptic proteins in the brain

Professor Seth Grant (PI - previous) and Dr Gareth Miles
Dr Matthew Broadhead (PDRA),
Centre for Neurodegeneration, University of Edinburgh and School of Psychology and Neuroscience, University of St. Andrews
Funded by Principals Career Development Scholarship

Gated stimulated emission depletion (g-STED) microscopy was used in this project to quantify PSD95eGFP organisation at the nanoscale in brain tissue to understand the underlying molecular framework of cognitive functions at the level of the synapse. This work was published in Nature Scientific Reports in May 2016 as part of a Wellcome Trust funded project at the University of Edinburgh. Matthew now works as a PDRA in St Andrews and continnues to collaborate with ESRIC.

STED MBFigure legend from above publication showing dye-filled neurons with single and multiple neuronal clusters in spine heads. Left panel, PSD95-eGFP (green) imaged with a confocal (Con) microscope and the Alexa Fluor 594-filled spine is shown in magenta. Right panel, g-STED image of PSD95-eGFP in same spine. Scale bars 500 nm.


ESRIC Publications:

2013/01 Nature Communications Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1



Hitesh Patel, Judith Zich, Bryan Serrels, Colin Rickman, Kevin G. Hardwick, Margaret C. Frame & Valerie G. Brunton
2013/02 The Journal of Biological Chemistry Munc18-1 protein molecules move between membrane molecular depots distinct from vesicle docking sites. 23223447 Annya M. Smyth, Lei Yang, Kirsty J. Martin, Charlotte Hamilton, Weiping Lu, Michael A. Cousin, Colin Rickman & Rory R. Duncan
2013/08 Science (New York N.Y.) Transcription. Flashing a light on the spatial organization of transcription. 23929972 Colin Rickman & Wendy A. Bickmore
2013/09 Frontiers in endocrinology Imaging large cohorts of single ion channels and their activity. 24027557 Katia Hiersemenzel, Euan R. Brown & Rory R. Duncan
2014/10 J Cell Sci Eps8 controls Src- and FAK-dependent phenotypes in squamous carcinoma cells. 25359883 Christina Schoenherr, Bryan Serrels, Charlotte Proby, Debbie L. Cunningham, Jane E. Findlay, George S. Baillie, John K. Heath & Margaret C. Frame
2014/12 Nature communications A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion. 25517944 Deirdre M. Kavanagh, Annya M. Smyth, Kirsty J. Martin, Alison Dun, Euan R. Brown, Sarah Gordon, Karen J. Smillie, Luke H. Chamberlain, Rhodri S. Wilson, Lei Yang, Weiping Lu, Michael A. Cousin, Colin Rickman & Rory R. Duncan
2015/03 Angewandte Chemie (International ed. in English) Rapid formation of a supramolecular polypeptide-DNA hydrogel for in situ three-dimensional multilayer bioprinting. 25656851 Chuang Li, Alan Faulkner-Jones, Alison R. Dun, Juan Jin, Ping Chen, Yongzheng Xing, Zhongqiang Yang, Zhibo Li, Wenmiao Shu, Dongsheng Liu & Rory R. Duncan
2015/06 Methods The evolution of structured illumination microscopy in studies of HIV. doi 10.1016/j.ymath.2015.06.007 26071977 Kelly Marnoc, Lara Al’Zoubic, Matthew Pearsona, b, Markus Poschd, Áine McKnightc & Ann P. Wheeler
2015/08 Histochemistry and Cell Biology Chromatin at the nuclear periphery and the regulation of genome functions 26170147 Charlene Lemaître & Wendy A. Bickmore
2015/09 eLife TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23). 26386247 Stephen LA, Tawamie H, Davis GM, Tebbe L, Nürnberg P, Nürnberg G, Thiele H, Thoenes M, Boltshauser E, Uebe S, Rompel O, Reis A, Ekici AB, McTeir L, Fraser A, Hall E, Mill P, Daudet N, Cross C, Wolfrum U, Jamra AR, Davey MG & Bolz HJ
2015/09 Genes & development A negative loop within the nuclear pore complex controls global chromatin organization. 26341556 Manuel Breuer & Hiroyuki Ohkura
2015/11 IEEE transactions on bio-medical engineering Estimation of Fluorescence Lifetimes via Rotational Invariance Techniques. 26571506 Yu H, Saleeb R, Dalgarno P & Day-Uei Li D.
2015/11 Scientific reports SIMcheck: a Toolbox for Successful Super-resolution Structured Illumination Microscopy. 26525406 Graeme Ball, Justin Demmerle, Rainer Kaufmann, Ilan Davis, Ian M. Dobbie & Lothar Schermelleh
2015/12 Biofabrication Three-dimensional bioprinting of complex cell laden alginate hydrogel structures. 26689257 Atabak Ghanizadeh Tabriz, Miguel A Hermida, Nicholas Leslie & Wenmiao Shu
2015/12 Cell reports ADF and Cofilin1 Control Actin Stress Fibers Nuclear Integrity and Cell Survival. 26655907 Georgios Kanellos, Jing Zhou, Hitesh Patel, Rachel A. Ridgway, David Huels, Christine B. Gurniak, Emma Sandilands, Neil O. Carragher, Owen J. Sansom, Walter Witke, Valerie G. Brunton & Margaret C. Frame
2016/01 Scientific reports Translation Microscopy (TRAM) for super-resolution imaging 26822455 Zhen Qiu, Rhodri S Wilson, Yuewei Liu, Alison R Dun, Rebecca S Saleeb, Dongsheng Liu, Colin Rickman, Margaret Frame, Rory R Duncan & Weiping Lu
2016/04 Scientific reports PSD95 nanoclusters are postsynaptic building blocks in hippocampus circuits. 27109929

Matthew J. Broadhead, Mathew H. Horrocks, Fei Zhu, Leila Muresan, Ruth Benavides-Piccione, Javier DeFelipe, David Fricker, Maksym V. Kopanitsa, Rory R. Duncan, David Klenerman, Noboru H. Komiyama, Steven F. Lee & Seth G. N. Grant

2016/05 American journal of human genetics A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence for Dominant-Negative Effect. 27108798 Meriel McEntagart1, Kathleen A. Williamson, Jacqueline K. Rainger, Ann Wheeler, Anne Seawright, Elfride De Baere, Hannah Verdin, L. Therese Bergendahl, Alan Quigley, Joe Rainger, Abhijit Dixit, Ajoy Sarkar, Eduardo López Laso, Rocio Sanchez-Carpintero, Jesus Barrio, Pierre Bitoun, Trine Prescott, Ruth Riise, Shane McKee, Jackie Cook, Lisa McKie, Berten Ceulemans, Françoise Meire, I. Karen Temple, Fabienne Prieur, Jonathan Williams, Penny Clouston, Andrea H. Németh, Siddharth Banka, Hemant Bengani, Mark Handley, Elisabeth Freyer, Allyson Ross, DDD Study, Veronica van Heyningen, Joseph A. Marsh, Frances Elmslie & David R. FitzPatrick
2016/08 Development Shh and ZRS enhancer co-localisation is specific to the zone of polarizing activity 23804033 Hitesh Patel, Judith Zich, Bryan Serrels, Colin Rickman, Kevin G. Hardwick, Margaret C. Frame & Valerie G. Brunton
2016/10 Genes and Development Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability


J Woodward, GC Taylor, DC Soares, S Boyle, D Sie, D Read, K Chathoth, M Vukovic, N Tarrats, D Jamieson, KJ Campbell, K Blyth, JC Acosta, B Yistra, MJ Arends, KR Kranc, AP Jackson, WA Bickmore, AJ Wood
2016/11 Open Biology SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neuralprogenitor cells 27852806 NS Benabdallah, P Gautier, B Hekiimoglu-Balkan, LA Lettice, S Bhatia & WA Bickmore
2016/11 Scientific Reports Smart-aggregation imaging for single molecule localisation with SPAD cameras 27876857 I Gyongy, A Davies, NA Dutton, RR Duncan, C Rickman, RK Henderson & PA Dalgarno
2017/01 Renal Physiology - American Journal of Physiology Bimodal dynamics of granular organelles in primary renin-expressing cells revealed using TIRFmicroscopy 28069661 C Buckley, AR Dun, A Peter, C Bellamy, KW Gross, RR Duncan & JJ Mullins
2017/01 Current Biology Navigation through the Plasma Membrane Molecular Landscape Shapes Random Organelle Movement 28089515 AR Dun, GJ Lord, RS Wilson, DM Kavanagh, KI Cialowivz, S Sugita, S Park, L Yang, AM Smyth, A Papadopulos, C Rickman & RR Duncan
2017/01 Scientific Reports Tryptophan and Non-Tryptophan Fluorescence of the Eye Lens Proteins Provides Diagnostics of Cataract at the Molecular Level 28071717 Anna Gakamsky, Rory R Duncan, Nicola M Howarth, Baljean Dhillon, Kim K Buttenschön, Daniel J Daly, and Dmitry Gakamsky
2017/01 Nature Communications Repo-Man/PP1 regulates heterochromatin formation in interphase
Inês J. de Castro, James Budzak, Maria L. Di Giacinto, Lorena Ligammari, Ezgi Gokhan, Christos Spanos, Daniela Moralli, Christine Richardson, Jose I. de las Heras, Silvia Salatino, Eric C. Schirmer, Katharine S. , Juri Rappsilber, Catherine GreenUllman, Wendy A. Bickmore, Sarah Lamble, Martin W. Goldberg, Veronica Vinciotti & Paola Vagnarelli
2017/03 eLife Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell invasion via trafficking networks 28362576 Christina Schoenherr, Adam Byron, Emma Sandilands, Ketevan Paliashvili, George S Baillie, Amaya Garcia-Munoz, Cristina Valacca, Francesco Cecconi, Bryan Serrels, and Margaret C Frame
2017/06  Cell SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs 28622508 Ryu-Suke Nozawa, LoraBoteva, Dinesh C Soares, Catherine Naughton, Alison R Dun, Adam Buckle, Bernard Ramsahoye, Peter C Bruton, Rebecca S Saleeb, Maria Arnedo, Bill Hill, Rory R Duncan, Sutherland K Maciver and Nick Gilbert
2017/10 Scientific Reports High-throughput assessment of mechanical properties of stem cell derived red blood cells toward cellular downstream processing 29089557 Ewa Guzniczak, Maryam Mohammad Zadeh, Fiona Dempsey, Melanie Jimenez, Henry Bock, Graeme Whyte, Nicholas Willoughby and Helen Bridle
2017/12 IEEE Trans. Electron Devices A 256 x 256 100-kfps 61% Fill-Factor SPAD Image Sensor for Time-Resolved Microscopy Applications doi:10.1109/TED.2017.2779790 Istvan Gyongy, Neil Calder, Amy Davies, Neale Dutton, Rory R. Duncan, Colin Rickman, Paul Dalgarno, Robert K. Henderson
2017/12 Scientific Reports A Bi-fluorescence complementation system to detect associations between the Endoplasmic reticulum and mitochondria 29234100 Mark Harmon, Philip Larkman, Giles Hardingham, Mandy Jackson and Paul Skehel
2018/01 The EMBO Journal Glyoxal as an alternative fixative to formaldehyde in immunostaining and super-resolution microscopy 29146773 Katharina N Richter, Natalia H Revelo, Katharina J Seitz, Martin S Helm, Deblina Sarkar, Rebecca S Saleeb, Elisa D'Este, Jessica Eberle, Eva Wagner, Christian Vogl, Diana F Lazaro, Frank Richter, Javier Coy‐Vergara, Giovanna Coceano, Edward S Boyden, Rory R Duncan, Stefan W Hell, Marcel A Lauterbach, Stephan E Lehnart, Tobias Moser, Tiago F Outeiro, Peter Rehling, Blanche Schwappach, Ilaria Testa, Bolek Zapiec, and Silvio O Rizzoli
2018/09 Nature Communications Super-silent FRET Sensor Enables Live Cell Imaging and Flow Cytometric Stratification of Intracellular Serine Protease Activity in Neutrophils
Thomas H. Craven, Nicolaos Avlonitis, Neil McDonald, Tashfeen Walton, Emma Scholefield, Ahsan R. Akram, Timothy S. Walsh, Chris Haslett, Mark Bradley & Kevin Dhaliwal
2018/09 The EMBO Journa Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis 30049712 Joel S Riley, Giovanni Quarato, Catherine Cloix, Jonathan Lopez, Jim O'Prey, Matthew Pearson, James Chapman, Hiromi Sesaki, Leo M Carlin, João F Passos, Ann P Wheeler, Andrew Oberst, Kevin M Ryan, Stephen WG Tait
2019/01 Journal of Biological Chemistry A VPS33A-binding motif on syntaxin17 controls autophagy completion in mammalian cells 30655294  R.S Saleeb, D.M. Kavanagh, A.R.Dun, P.A.Dalgarno, R.R. Duncan