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 (if you have published using the ESRIC facilities and your publication is not listed please get in touch with This email address is being protected from spambots. You need JavaScript enabled to view it. or if you are registered as an ESRIC user enter it here.

Cellular communication and diabetes

Dr Colin Rickman
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 Cros Correlation Spectroscopy to study SNARE protein interactions in neuronal cells.

DeeFigure panel from: A molecular toggle after exocytosis sequesters the presynaptic ‚Äčsyntaxin1a 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. 

Protein-Protein interactions in the NMD pathway

Professor Javier Caceres (PI)
Dr Dasa Longmann (PDRA)
Human Genetics Unit, University of Edinburgh
Funded by MRC

NMD (Nonsense-mediated mRNA Decay) is an mRNA quality control pathway that ensures rapid degradation of mRNAs that carry premature termination codons, and also modulates expression of a large number of physiological transcripts. The progression of this pathway is governed by dynamic assembly of NMD complexes that leads to degradation of targeted transcript. This project uses FRET-FLIM to investigate direct protein-protein interactions between the core NMD factor UPF1 and other factors that play role in this pathway.

 

Investigating epithelial cell mechanics

Dr Yuang Chen and Dr Nik Willoughby (PI)
Jessica Barkhuissen (PhD student) 
Institute of Biological Chemistry, Bioengineering and Biophysics, Heriot-Watt University
Funded by EPSRC

This project aims to investigate the mechanical properties of particular cell types at a multi-cellular, rather than single cell level, to further understand how interactions at a cellular level can be translated into whole organ structure. Cellular mechanics are investigated using Atomic Force Microscopy.

Combined StacksJBAFM Force map overlay for height measured of an MDCK cell cluster. Channel display (Height of cell sample after deformation). 

ESRIC Publications:

2013/01 Nature communications Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1. 23804033 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

27737961

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