Cell Communication

Members

Summary

Research within this group explores the role of cell communication in both eukaryotes and prokaryotes. A multidisciplinary approach is used to investigate cellular adaptation and differentiation in response to both physiological and pathophysiological stimuli. In mammalian systems, communication influences a variety of cellular processes including host inflammatory responses, cell survival, reproduction and stem cell biology.

Research focuses on understanding how host inflammatory responses are regulated in a range of pathologies. Areas of interest include the role of oxidative/nitrosative stress and understanding the transmission of nitric oxide related signals via S-nitrosothiols, with the aim of developing nitric oxide replacement therapies for cardiovascular disease.

Melanocortin and annexin peptides mediate anti-inflammatory effects and ongoing research aims to develop novel therapeutics in a range of pathologies including stroke, arthritis and respiratory disorders including asthma and COPD.

Research programmes in the area of reproduction include the hypothalamic control of the reproductive axis, the role of hypoxia in the ovarian follicle development and the role of melanocortins in the male and female reproductive systems.

Studies of stem cell differentiation have looked for novel markers such as the STRO-1 antigen and ongoing projects are investigating the role of nitric oxide signalling during mesenchymal stem cell differentiation.

In addition to identification of novel therapeutics, we are actively identifying biomarkers for disease pathologies, which include: identification of annexin 1 (glucocorticoid-induced anti-inflammatory protein) in human saliva as a potential predictive marker for oral disease and a biomarker platform based on proteomic/glycomic technologies allowing the identification of novel molecules implicated in breast and colorectal cancer metastasis. There is also interest within the group exploring metagenomic profiling and the development of rapid diagnostic tools.

Images

Cell communication - responding to change.
Lipid droplets accumulating in an adipocyte cell line.

Oil red O staining:

Differentiated

Undifferentiated

Aspergillus, cultured for 72 hours and stained with Celltrace Calcein red-orange (magnification x10)

Recent Publications

Complete lists of publications are available on each staff members site.

Xiao F, Gordge MP. Cell surface protein disulphide isomerase may explain the platelet-selective action of S-nitrosoglutathione. Nitric Oxide: Biology and Chemistry (2011) 25: 303-308

Gordge MP, Xiao F. S-nitrosothiols as selective antithrombotic agents – possible mechanisms. Br J Pharmacol (2010) 159(8):1572-80.

Leoni G, Voisin MB, Carlson K, Getting S, Nourshargh S, Perretti M. The melanocortin MC(1) receptor agonist BMS-470539 inhibits leucocyte trafficking in the inflamed vasculature. Br J Pharmacol. 2010 160(1):171-80.

Farnaud SJ, Kosti O, Getting SJ, Renshaw D. Saliva: physiology and diagnostic potential in health and disease. ScientificWorldJournal. 2010 Mar 16;10:434-56.

Getting SJ, Kaneva M, Bhadresa Y, Renshaw D, Leoni G, Patel HB, Kerrigan PM, Locke IC. Melanocortin peptide therapy for the treatment of arthritic pathologies. ScientificWorldJournal. 2009 Dec 16;9:1394-414

Sheetal Raina*, Daniela De Vizio*, Mark Odell*, Mark Clements*, Sophie Vanhulle and Tajalli Keshavarz* - Microbial quorum sensing: a tool or a target for antimicrobial therapy?” Biotechnology and Applied Biochemistry (2009) 54, (65–84)

Getting SJ, Riffo-Vasquez Y, Pitchford S, Kaneva M, Grieco P, Page CP, Perretti M, Spina D. A role for MC3R in modulating lung inflammation. Pulm Pharmacol Ther. 2008 Dec;21(6):866-73.

Leoni G, Patel HB, Sampaio AL, Gavins FN, Murray JF, Grieco P, Getting SJ, Perretti M. Inflamed phenotype of the mesenteric microcirculation of melanocortin type 3 receptor-null mice after ischemia-reperfusion. Faseb J. (2008) ;22(12):4228-38.

Farnaud S, Amini M, Rapisarda C, Cammack R, Bui T, Drake A, Evans RW, Rahmanto YS, Richardson DR. Biochemical and spectroscopic studies of human melanotransferrin (MTf): Electron-paramagnetic resonance evidence for a difference between the iron-binding site of MTf and other transferrins. Int J Biochem Cell Biol. (2008) 40:2739-45. 

Farnaud S, Rapisarda C, Bui T, Drake A, Cammack R, Evans RW. Identification of an iron-hepcidin complex. Biochem J. (2008) 413: 553-7.

Conesa C, Sánchez L, Rota C, Pérez MD, Calvo M, Farnaud S, Evans RW. Isolation of lactoferrin from milk of different species: calorimetric and antimicrobial studies. Comp Biochem Physiol B Biochem Mol Biol. (2008) 150:131-9.

Junkes C, Wessolowski A, Farnaud S, Evans RW, Good L, Bienert M, Dathe M. The interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranes. J Pept Sci. (2008) 14(4): 535-43.

Crabtree MJ, Smith CL, Lam G, Goligorsky MS, Gross SS. Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS. Am J Physiol Heart Circ Physiol. (2008) 294(4):H1530-40.

Murphy T, Roy I, Harrop A, Dixon K, Keshavarz T. Elicitation effects of oligosaccharides on the transcriptional level of bacitracin ABC transporter genes in Bacillus licheniformis. Biotechnol Lett. (2008) 30(9):1665-70.

Kerrigan MJ, Hall AC. Control of chondrocyte regulatory volume decrease (RVD) by [Ca2+]i and cell shape. Osteoarthritis Cartilage. (2008) 16(3):312-22.

Chen Y, Leask A, Abraham DJ, Pala D, Shiwen X, Khan K, Liu S, Carter DE, Wilcox-Adelman S, Goetinck P, Denton CP, Black CM, Pitsillides AA, Sarraf CE, Eastwood M. Heparan sulfate-dependent ERK activation contributes to the overexpression of fibrotic proteins and enhanced contraction by scleroderma fibroblasts. Arthritis Rheum. (2008) 58 (2):577-85.

Abstracts 2008-2009

Fawdar S and Clements MO. Characterisation of STRO-1 expression on human Mesenchymal Stem Cells. 3rd UK Mesenchymal Stem Cell Meeting, Sheffield, January 2009.

Stenbeck G, Joseph J, Getting SJ and Smith CL. Asymmetric dimethylarginine negatively influences osteoblast differentiation in vitro. British Pharmacological Society, Winter meeting, December 2008, C041.

Getting SJ, Kaneva M and Kerrigan M. A role for melanocortin peptides in modulating oxidative stress induced inflammation in A549 cells. British Pharmacological Society, Winter meeting, December 2008, C020.

Wotherspoon G, Yogarajah S, Lynch S, Smith C, Getting SJ, Perretti M and Murray JF. Melanocortin 3 receptor in the testes of mice. British Pharmacological Society, Winter meeting, December 2008, P008.

Nadelcheva Y, Getting SJ and Kerrigan M. The role of the actin cytoskeleton in chondroctye protection following single impact. British Pharmacological Society, Winter meeting, December 2008, P101.

Shah C, Bell A & Gordge M. Reversible inhibition of cell surface protein disulphide isomerase by NO donor compounds. 9th UK Nitric Oxide Forum, August 2008.

Current Grants

Dr Joanne Murray - Awarded January 2009. Society for Endocrinology 11895 "Melanocortin-3 receptors in the testis".

Dr Miriam Dwek - 2008 Cancer Research

Dr Mike Gordge - 2008 British Heart Foundation

Dr Joanne Murray - 2008 The Wellcome Trust