a state of the art facility for the study of protein trafficking in vivo
Lead Research Organisation:
University of Leeds
Department Name: Institute of Membrane & Systems Biology
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Determining protein localisation and dynamics is important for answering many questions in biology. To understand how proteins function and are regulated in vivo, we need approaches by which we can determine where proteins go and when, as well as when and where two proteins interact. New and emerging technologies will go a long way towards helping us answer these questions. The first is the development of photo-activatable GFP (PA-GFP). By tagging proteins with PA-GFP, and then using photo-activation to observe a subset of fluorescently labelled molecules on a low fluorescent background, their fate can be accurately determined. The second is the recent developments in the GFP and RFP fluorophores that have improved behaviour in FRET, enabling us to use this approach to investigate protein-protein interactions in vivo. Furthermore, microscopy is now being developed as a tool for high throughput screening approaches, to investigate the effects of mutations, or for screening large numbers of small molecules for ones that have useful effects in cell biology. The major goal of this application is to upgrade our existing bio-imaging facility into a state-of-the-art facility that can exploit these new technologies, with the focus of studying protein trafficking in vivo.
Publications
Scott DJ
(2011)
Clot architecture is altered in abdominal aortic aneurysms and correlates with aneurysm size.
in Arteriosclerosis, thrombosis, and vascular biology
Xia R
(2008)
Inhibitory interaction between P2X4 and GABA(C) rho1 receptors.
in Biochemical and biophysical research communications
Smith AJ
(2006)
Increased ATP-sensitive K+ channel expression during acute glucose deprivation.
in Biochemical and biophysical research communications
Baker A
(2010)
Peroxisome biogenesis and positioning.
in Biochemical Society transactions
Turrell SJ
(2012)
Cellular uptake of highly-functionalized ruthenium(II) tris-bipyridine protein-surface mimetics.
in Bioorganic & medicinal chemistry letters
Smith KA
(2011)
Interactions between factor XIII and the alphaC region of fibrinogen.
in Blood
Henderson Z
(2010)
Co-localization of PRiMA with acetylcholinesterase in cholinergic neurons of rat brain: an immunocytochemical study.
in Brain research
Bahnasi YM
(2008)
Modulation of TRPC5 cation channels by halothane, chloroform and propofol.
in British journal of pharmacology
Dove B
(2006)
Changes in nucleolar morphology and proteins during infection with the coronavirus infectious bronchitis virus
in Cellular Microbiology
McHale R
(2010)
Prussian blue coordination polymer nanobox synthesis using miniemulsion periphery polymerization (MEPP).
in Chemical communications (Cambridge, England)
Naylor J
(2010)
Pregnenolone sulphate- and cholesterol-regulated TRPM3 channels coupled to vascular smooth muscle secretion and contraction.
in Circulation research
Li J
(2011)
Orai1 and CRAC channel dependence of VEGF-activated Ca2+ entry and endothelial tube formation.
in Circulation research
Boyne JR
(2006)
gamma-2 Herpes virus post-transcriptional gene regulation.
in Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
Griffiths RA
(2006)
Herpesvirus saimiri-based gene delivery vectors.
in Current gene therapy
Hess K
(2012)
A novel mechanism for hypofibrinolysis in diabetes: the role of complement C3.
in Diabetologia
Ghosh SR
(2010)
Determination of the mobility of novel and established Caenorhabditis elegans sarcomeric proteins in vivo.
in European journal of cell biology
Smith AJ
(2010)
Voltage-dependent charge movement associated with activation of the CLC-5 2Cl-/1H+ exchanger.
in FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Harrison SM
(2007)
Characterisation of cyclin D1 down-regulation in coronavirus infected cells.
in FEBS letters
Boyne JR
(2009)
Nucleolar disruption impairs Kaposi's sarcoma-associated herpesvirus ORF57-mediated nuclear export of intronless viral mRNAs.
in FEBS letters
Dalton JE
(2006)
Intraepithelial gammadelta+ lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection.
in Gastroenterology
Taneja TK
(2009)
Sar1-GTPase-dependent ER exit of KATP channels revealed by a mutation causing congenital hyperinsulinism.
in Human molecular genetics
Hong Y
(2011)
Herpesvirus saimiri-based endothelin-converting enzyme-1 shRNA expression decreases prostate cancer cell invasion and migration.
in International journal of cancer
Hong Y
(2012)
The impact of amyloid precursor protein signalling and histone deacetylase inhibition on neprilysin expression in human prostate cells.
in International journal of cancer
Macnab SA
(2011)
Herpesvirus saimiri-mediated delivery of the adenomatous polyposis coli tumour suppressor gene reduces proliferation of colorectal cancer cells.
in International journal of oncology
Manna P
(2010)
Constitutive Endocytic Recycling and Protein Kinase C-mediated Lysosomal Degradation Control KATP Channel Surface Density
in Journal of Biological Chemistry
Turrell SJ
(2011)
Mutation of herpesvirus Saimiri ORF51 glycoprotein specifically targets infectivity to hepatocellular carcinoma cell lines.
in Journal of biomedicine & biotechnology
Dunn S
(2008)
Differential trafficking of Kif5c on tyrosinated and detyrosinated microtubules in live cells
in Journal of Cell Science
Street M
(2006)
Stimulation of Galphaq-coupled M1 muscarinic receptor causes reversible spectrin redistribution mediated by PLC, PKC and ROCK.
in Journal of cell science
Musa H
(2006)
Targeted homozygous deletion of M-band titin in cardiomyocytes prevents sarcomere formation.
in Journal of cell science
Swailes NT
(2006)
Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse.
in Journal of cell science
Peckham M
(2008)
Engineering a multi-nucleated myotube, the role of the actin cytoskeleton.
in Journal of microscopy
Emmott E
(2010)
Quantitative proteomics using SILAC coupled to LC-MS/MS reveals changes in the nucleolar proteome in influenza A virus-infected cells.
in Journal of proteome research
Reed ML
(2007)
Characterization of the nuclear export signal in the coronavirus infectious bronchitis virus nucleocapsid protein.
in Journal of virology
Taylor A
(2011)
Mutation of a C-terminal motif affects Kaposi's sarcoma-associated herpesvirus ORF57 RNA binding, nuclear trafficking, and multimerization.
in Journal of virology
Dove B
(2006)
Cell cycle perturbations induced by infection with the coronavirus infectious bronchitis virus and their effect on virus replication.
in Journal of virology
Groppelli E
(2010)
Cell entry of the aphthovirus equine rhinitis A virus is dependent on endosome acidification.
in Journal of virology
Smith AJ
(2008)
Investigation of K(ATP) channel endocytosis by immunofluorescence.
in Methods in molecular biology (Clifton, N.J.)
Wu W
(2012)
Different NF-?B activation characteristics of human respiratory syncytial virus subgroups A and B.
in Microbial pathogenesis
Xu SZ
(2008)
TRPC channel activation by extracellular thioredoxin.
in Nature
Henderson Z
(2010)
Distribution and role of Kv3.1b in neurons in the medial septum diagonal band complex.
in Neuroscience
Rose K
(2011)
Transcriptional repression of the M channel subunit Kv7.2 in chronic nerve injury.
in Pain
Prandovszky E
(2011)
The neurotropic parasite Toxoplasma gondii increases dopamine metabolism.
in PloS one
Mankouri J
(2010)
Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.
in PLoS pathogens
Jackson BR
(2011)
An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export.
in PLoS pathogens
Description | The aim of this project was to improve our ability to use light microscopy to image cells, and within cells. The funding allowed us to buy additional equipment to upgrade our existing confocal microscopes, so that we could improve our imaging. These microscopes are used by over 20 different research groups within the Faculty of Biological Sciences at the University, and have supported a wide range of research, from imaging organelles and how they move in living plants, to imaging receptors in mammalian cells. |
Exploitation Route | The research can be used by those interested in developing treatments for infections and disease (e.g. pharma companies, clinicians). Imaging is central to understanding the healthy human organism, plants and animals. Without knowledge of how things work, it is very difficult to understand what goes wrong in disease states. The new microscopes are essential for using imaging to understand cellular processes, and in detecting what goes wrong in diseases from virus infections, to inherited mutant |
Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
URL | http://www.fbs.leeds.ac.uk/facilities/bioimaging/ |
Description | This funding provided an upgrade to our bio-imaging facility which is used by over 40 different research groups across biological sciences and medicine. It has had impact in a broad range of healthcare and biological sciences. |
First Year Of Impact | 2007 |
Sector | Healthcare,Other |
Impact Types | Economic |