Phil Hill

Contact

• workFood Sciences
  Sutton Bonington Campus
  Sutton Bonington
  Leicestershire
  LE12 5RD
  UK
• work0115 951 6169
• fax0115 951 6162
• phil.hill@nottingham.ac.uk

Research Summary

Understanding the biological mechanisms underlying the way in which genes are switched on and off in different circumstances is fundamental to improving our knowledge of the regulation of important… read more

Selected Publications

• HILL PJ, STRITZKER J, SCADENG M, GEISSINGER U, HADDAD D, BASSE-LÜSEBRINK TC, GBURECK U, JAKOB P and SZALAY AA, 2011. Magnetic Resonance Imaging Of Tumors Colonized With Bacterial Ferritin-Expressing Escherichia Coli. Plos One. 6(10), e25409
• QAZI, S.N.A., HARRISON, S.E., SELF, T., WILLIAMS, P. and HILL, P.J., 2004. Real-time monitoring of intracellular Staphylococcus aureus replication Journal of Bacteriology. 186(4), 1065-1077
• QAZI, S.N.A., COUNIL, E., MORRISSEY, J., REES, C.E.D., COCKAYNE, A., WINZER, K., CHAN, W.C., WILLIAMS, P. and HILL, P.J., 2001. <i>agr</i> expression precedes escape of internalized <i>Staphylococcus aureus</i> from the host endosome Infection and Immunity. 69(11), 7074-7082
• PEREHINEC,, QAZI,, GADDIPATI,, SALISBURY,, REES, and HILL,, 2007. Construction and evaluation of multisite recombinatorial (Gateway) cloning vectors for Gram-positive bacteria. 8(1), 80

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Current Research

Understanding the biological mechanisms underlying the way in which genes are switched on and off in different circumstances is fundamental to improving our knowledge of the regulation of important biological responses in disease. For instance, when bacteria are ingested they may sense a change in their environment which leads them to express virulence determinants which help them to evade host defences, invade tissues or otherwise cause disease in the host.

Part of my research group's interest is the development of 'in situ' reporter/marker systems in bacteria, which lets us track organisms and allow expression of their genes to be measured in real time, without destruction of the organisms under investigation. We have developed high-level lux (bacterial bioluminescence) and gfp (green fluorescent protein) expression systems for both Gram positive and Gram negative organisms, as well as dual-reporter operons to exploit the complementary advantages of each of these reporter systems simultaneously. Using these tools we have developed high-throughput procedures to directly interrogate bacterial replication and gene expression of intracellular bacteria such as Listeria and Staphylococcus whilst they are inside mammalian cells.

Using the above approaches and other modern molecular biological techniques we are studying the way bacteria respond and adapt to changing environments. For example, we study the global regulation of genes in staphylococci under iron deficiency, an environmental signal encountered by any organism when introduced into a mammalian body which may induce production of virulence determinants. Also in this programme we are investigating the way that staphylococci use quorum sensing mechanisms to modulate their virulence gene expression while they are in intimate contact with mammalian cells.

More recently I have been working on aspects of microbial interactions with different kinds of cancers. This includes the use of reporter microorganisms to give a rapid chemosensitivity test. This allows a patient's individual dose response to chemotherapy to be assessed before treatment, making it possible to avoid using ineffective drugs, so sparing patients the side effects normally associated with these agents. Chemosensitivity testing also allows the selection of drugs which are effective in the laboratory so offering patients a better chance of response.

A further aspect of this work is the development of 'reporter genes' for MRI imaging. Combined with microorganisms that can naturally target and replicate in solid tumours this approach may lead to an improvement in diagnostic imaging.

• HILL PJ, STRITZKER J, SCADENG M, GEISSINGER U, HADDAD D, BASSE-LÜSEBRINK TC, GBURECK U, JAKOB P and SZALAY AA, 2011. Magnetic Resonance Imaging Of Tumors Colonized With Bacterial Ferritin-Expressing Escherichia Coli. Plos One. 6(10), e25409
• STRITZKER, JOCHEN, HILL, PHILIP J, GENTSCHEV, IVAYLO and SZALAY, ALADAR A, 2010. Myristoylation negative msbB-mutants of probiotic E. coli Nissle 1917 retain tumor specific colonization properties but show less side effects in immunocompetent mice. Bioengineered bugs. 1(2), 139-145
• STRITZKER, JOCHEN, WEIBEL, STEPHANIE, SEUBERT, CAROLIN, GÖTZ, ANDREAS, TRESCH, ACHIM, VAN ROOIJEN, NICO, OELSCHLAEGER, TOBIAS A, HILL, PHILIP J, GENTSCHEV, IVAYLO and SZALAY, ALADAR A, 2010. Enterobacterial tumor colonization in mice depends on bacterial metabolism and macrophages but is independent of chemotaxis and motility. International journal of medical microbiology : IJMM.
• THURMAN, JILL, PARRY, JACQUELINE D, HILL, PHILIP J and LAYBOURN-PARRY, JOHANNA, 2010. The Filter-Feeding Ciliates Colpidium striatum and Tetrahymena pyriformis Display Selective Feeding Behaviours in the Presence of Mixed, Equally-Sized, Bacterial Prey. Protist.
• ALLOUSH, HABIB M, ANDERSON, ELIZABETH, MARTIN, ASHLEY D, RUDDOCK, MARK W, ANGELL, JOHANNA E, HILL, PHIL J, MEHTA, PRIYANKA, SMITH, M ANN, SMITH, J GRAHAM and SALISBURY, VYV C, 2010. A bioluminescent microbial biosensor for in vitro pretreatment assessment of cytarabine efficacy in leukemia. Clinical chemistry. 56(12), 1862-70
• BELISLE JT, MAHAFFEY SB and HILL PJ, 2009. Isolation Of Mycobacterium Species Genomic Dna. Methods In Molecular Biology (Clifton, N.J.). 465, 1-12
• TORRELLES JB, KNAUP R, KOLARETH A, SLEPUSHKINA T, KAUFMAN TM, KANG P, HILL PJ, BRENNAN PJ, CHATTERJEE D, BELISLE JT, MUSSER JM and SCHLESINGER LS, 2008. Identification Of Mycobacterium Tuberculosis Clinical Isolates With Altered Phagocytosis By Human Macrophages Due To A Truncated Lipoarabinomannan. The Journal Of Biological Chemistry. 283(46), 31417-28
• BASARAB GS, HILL PJ, RASTAGAR A and WEBBORN PJH, 2008. Design Of Helicobacter Pylori Glutamate Racemase Inhibitors As Selective Antibacterial Agents: A Novel Pro-Drug Approach To Increase Exposure. Bioorganic & Medicinal Chemistry Letters. 18(16), 4716-22
• SIELING PA, HILL PJ, DOBOS KM, BROOKMAN K, KUHLMAN AM, FABRI M, KRUTZIK SR, REA TH, HEASLIP DG, BELISLE JT and MODLIN RL, 2008. Conserved Mycobacterial Lipoglycoproteins Activate Tlr2 But Also Require Glycosylation For Mhc Class Ii-Restricted T Cell Activation. Journal Of Immunology (Baltimore, Md. : 1950). 180(9), 5833-42
• STRITZKER, J., WEIBEL, S., HILL, P.J., OELSCHLAEGER, T.A., GOEBEL, W. and SZALAY, A..A., 2007. Tumor-specific colonization, tissue distribution, and gene induction by probiotic <i>Escherichia coli</i> Nissle 1917 in live mice International Journal of Medical Microbiology. 297(3), 151-162
• PEREHINEC,, QAZI,, GADDIPATI,, SALISBURY,, REES, and HILL,, 2007. Construction and evaluation of multisite recombinatorial (Gateway) cloning vectors for Gram-positive bacteria. 8(1), 80
• SZALAY, AA, HILL, PJ, KRICKA, LJ and STANLEY, PE., eds., 2007. Bioluminescence & Chemiluminescence:: Chemistry, Biology & Applications World Scientific Publishing Co. Pte. Ltd..
• QAZI, S., MIDDLETON, B., MUHARRAM, S.H., COCKAYNE, A., HILL, P., O'SHEA, P., CHHABRA, S.R., CAMARA, M. and WILLIAMS, P., 2006. N-acylhomoserine lactones antagonize virulence gene expression and quorum sensing in staphylococcus aureus Infection and Immunity. 74(2), 910-919
• PATEL, A., CUMMINGS, N., BATCHELOR, M., HILL, P.J., DUBOIS, T., MELLITS, K.H., FRANKEL, G. and CONNERTON, I., 2006. Host protein interactions with enteropathogenic Escherichia coli (EPEC) : 14-3-3 tau binds Tir and has a role in EPEC-induced actin polymerization Cellular Microbiology. 8(1), 55-71
• HARRAGHY, S., KORMANEC, S., WOLZ, S., HOMEROVA, S., GOERKE, S., OHLSEN, S., QAZI, S.N., HILL, P.J. and HERRMANN, P., 2005. 'sae' is essential for the expression of the staphlococcal adhesins Eap and Emp Microbiology. 151(6), 1725-2118
• EDWARDS, C.V., HILL, P., SCAMMELL, B.E. and BAYSTON, R., 2005. A DNA vaccine for prevention of Staphylococcus aureus infection in orthopaedic infection. Journal of Bone and Joint Surgery (British). 87B(Supplement 3), 303
• QAZI, S.N.A., HARRISON, S.E., SELF, T., WILLIAMS, P. and HILL, P.J., 2004. Real-time monitoring of intracellular Staphylococcus aureus replication Journal of Bacteriology. 186(4), 1065-1077
• GILBERT, J.A., HILL, P.J., DODD, C.E.R. and LAYBOURN-PARRY, J., 2004. Demonstration of antifreeze protein activity in Antarctic lake bacteria Microbiology. 150(1), 171-180
• FREES D, CHASTANET, A, QAZI, S, SØRENSEN, K, HILL, P, MSADEK, T and INGMER, H., 2004. Clp ATPases are required for stress tolerance, intracellular replication, and biofilm formation in Staphylococcus aureus Molecular Microbiology. 54(5), 1445–1462
• ERCOLINI, D., HILL, P.J. and DODD, C.E.R., 2003. Bacterial community structure and location in Stilton cheese Applied and Environmental Microbiology. 69(6), 3540-3548
• ERCOLINI, D., HILL, P.J. and DODD, C.E., 2003. Development of a fluorescence in situ hybridization method for cheese using a 16S rRNA probe Journal of Microbiological Methods. VOL 52(NUMBER 2), 267-271
• FREES, D., QAZI, S.N.A., HILL, P.J. and INGMER, H., 2003. Alternative roles of ClpX and ClpP in <i>Staphylococcus aureus</i> stress tolerance and virulence Molecular Microbiology. VOL 48(PART 6), 1565-1578
• MORRISSEY, J.A., COCKAYNE, A., HAMMACOTT, J., BISHOP, K., DENMAN-JOHNSON, A., HILL, P.J. and WILLIAMS, P., 2002. Conservation, surface exposure, and in vivo expression of the Frp family of iron-regulated cell wall proteins in <i>Staphylococcus aureus</i>. Infection and Immunity. 70(5), 2399-2407
• WINZER, K., HARDIE, K.R., BURGESS, N., DOHERTY, N., KIRKE, D., HOLDEN, M.T.G., LINFORTH, R., CORNELL, K.A., TAYLOR, A.J., HILL, P.J. and WILLIAMS P., 2002. LuxS: its role in central metabolism and the <i>in vitro</i> synthesis of 4-hydroxy-5-methyl-3(2H)-furanone Microbiology. 148(4), 909-922
• MCDOWELL, P., AFFAS, Z., REYNOLDS, C., HOLDEN, M.T.G., WOOD, S.J., SAINT, S., COCKAYNE, A., HILL, P.J., DODD, C.E.R., BYCROFT, B.W., CHAN, W.C. and WILLIAMS, P., 2001. Structure, activity and evolution of the group I thiolactone peptide quorum-sensing system of <i>Staphylococcus aureus</i> Molecular Microbiology. 41(2), 503-512
• QAZI, S.N.A., COUNIL, E., MORRISSEY, J., REES, C.E.D., COCKAYNE, A., WINZER, K., CHAN, W.C., WILLIAMS, P. and HILL, P.J., 2001. <i>agr</i> expression precedes escape of internalized <i>Staphylococcus aureus</i> from the host endosome Infection and Immunity. 69(11), 7074-7082
• GOTSCHLICH, A., HUBER, B., GEISENBERGER, O., TOGL, A., STEIDLE, A., RIEDEL, K., HILL, P., TUMMLER, B., VANDAMME, P., MIDDLETON, B., CAMARA, M., WILLIAMS, P., HARDMAN, A. and EBERL, L., 2001. Synthesis of multiple N-acylhomoserine lactones is wide-spread among the members of the Burkholderia cepacia complex Systematic and Applied Microbiology. 24(1), 1-14
• QAZI, S. N. A., REES, C. E. D., MELLITS, K. H. and HILL, P. J., 2001. Development of gfp Vectors for Expression in Listeria monocytogenes and Other Low G+C Gram Positive Bacteria MICROBIAL ECOLOGY -NEW YORK-. VOL 41(PART 4), 301-309
• MORRISSEY, J. A., COCKAYNE, A., HILL, P. J. and WILLIAMS, P., 2000. Molecular Cloning and Analysis of a Putative Siderophore ABC Transporter from Staphylococcus aureus Infection and Immunity. VOL 68(PART 11), 6281-6288
• BAILEY, M., CORBISIER, P., GLOVER, A., HILL, P.J., JANSSON, J.K., KILLHAM, K., LINDOW, S., MOLIN, S., OLIVER, J., PROSSER, J., PALOMARES, A., TEBBE, C. and VAN ELSAS, J.D., 2000. Reporter genes for monitoring microbial cell activity and/or the environment. An opinion sponsered by the European Commission Biotechnology Programme, DGXII
• CIARCIAGLINI, G., HILL, P. J., DAVIES, K., MCCLURE, P. J., KILSBY, D., BROWN, M. H. and COOTE, P. J., 2000. Germination-Induced Bioluminescence, a Route To Determine the Inhibitory Effect of a Combination Preservation Treatment on Bacterial Spores Applied and Environmental Microbiology. VOL 66(PART 9), 3735-3742
• HOLDEN, M. T. G., CHHABRA, S. R., DE NYS, R., STEAD, P., BAINTON, N. J., HILL, P. J., MANEFIELD, M., KUMAR, N., LABATTE, M. and ENGLAND, D., 1999. Quorum-sensing cross talk: isolation and chemical characterization of cyclic dipeptides from Pseudomonas aeruginosa and other Gram-negative bacteria Molecular Microbiology. VOL 33(NUMBER 6), 1254-1266
• HILL, P. and STANLEY, P., 1999. In Memoriam: Gordon Sydney Anderson Birnie Stewart (1951-1999) LUMINESCENCE -CHICHESTER-. VOL 14(NUMBER 5), 235-238
• HILL, P. J., COCKAYNE, A., LANDERS, P., MORRISSEY, J. A., SIMS, C. M. and WILLIAMS, P., 1998. SirR, a Novel Iron-Dependent Repressor in Staphylococcus epidermidis Infection and Immunity. VOL 66(NUMBER 9), 4123-4129
• COCKAYNE, A., HILL, P. J., POWELL, N. B. L., BISHOP, K., SIMS, C. and WILLIAMS, P., 1998. Molecular Cloning of a 32-Kilodalton Lipoprotein Component of a Novel Iron-Regulated Staphylococcus epidermidis ABC Transporter Infection and Immunity. VOL 66(NUMBER 8), 3767-3774
• HILL, P.J., BYCROFT, B.W., SIMS, C.M., GRIESMAYR, G., STEWART, G.S., WILLIAMS, P., WINSON, M.K. and SWIFT, S., 1998. Engineering the <em>luxCDABE</em> genes from <em>Photorhabdus luminescens) to provide a bioluminescent reporter for constitutive and promotor probe plasmids and mini-Tn</em>5 constructs FEMS Microbiology Letters. 163, 193-202
• STEWART, G.S., HILL, P.J., LOESSNER, M. and SCHERER, S., 1998. Bacterial bioluminescence: A forward perspective. In: A practical guide to industrial uses of ATP-luminescence in Rapid Microbiology Cara Technology Ltd, East Grinstead, UK. 115-123
• DE LORENZO, V., GLOVER, A., HILL, P.J., JANSSON, J.K., JORGENSON, K., MERGEAY, M., MOLIN, S., MORGAN, A., NYBROE, O., OLIVER, J., PROSSER, J., ROMANTSHUK, M., SELBITSCHKA, W., TEBBE, C. and TOP, E., 1998. Marker genes as tags for monitoring microorganisms in nature.
• HILL, P. J., HALL, L., VINICOMBE, D. A. and SOPER, C. J., 1994. Bioluminescence and spores as biological indicators of inimical processes Journal of Applied Bacteriology. VOL 76(NUMBER SUP), 129S
• HILL, P. J. and STEWART, G. S. A. B., 1994. Use of Lux Genes in Applied Biochemistry JOURNAL OF BIOLUMINESCENCE AND CHEMILUMINESCENCE. VOL 9(NUMBER 3), 211
• SWIFT,S., WINSON,M.K., CHAN,P.F., BAINTON,N.J., BIRDSALL,M., REEVES,P.J., REES,C.E.D., CHHABRA,S.R., HILL,P.J., THROUP,J.P., BYCROFT,B.W., SALMOND,G.P.C., WILLIAMS,P. and STEWART,G.S.A.B, 1993. A novel strategy for the isolation of luxI homologues: evidence for the widespread distribution of a LuxR:LuxI superfamily in enteric bacteria Molecular Microbiology. 10(3), 511-520
• SEYMOUR, G. B., FRAY, R. G., HILL, P. and TUCKER, G. A., 1993. Down-regulation of two non-homologous endogenous tomato genes with a single chimaeric sense gene construct Plant Molecular Biology. VOL 23(NUMBER 1), 1
• BAINTON,N.J., BYCROFT,B., CHHABRA,S., STEAD,P., GLEDHILL,L., HILL,P.J., REES,C.E.D., WINSON,M.K., SALMOND,G.P.C., STEWART,G.S.A.B. and WILLIAMS,P, 1992. A general role for the lux autoinducer in bacterial cell signalling -control of antibiotic synthesis in Erwinia Gene. 116(1), 87-91
• STARBUCK, M., HILL, P.J. and STEWART, G.S., 1992. Ultra-sensitive detection of Listeria monocytogenes in milk by the polymerase chain reaction (PCR) Letters in Applied Microbiology. 15, 248-252
• HILL, P.J., SWIFT, S. and STEWART, G.S., 1991. PCR based gene engineering of the Vibrio harveyi lux operon and the Escherichia coli trp operon provides for biochemically functional native and fused gene products Molecular and General Genetics. 226, 41-48
• JACOBS, M., HILL, P.J. and STEWART, G.S., 1991. Highly bioluminescent Bacillus subtilis obtained through high-level expression of a luxAB fusion gene. Molecular and General Genetics. 230, 251-256