Professor David Hornby
School of Biosciences
Professor of Biochemistry
+44 114 222 4232
Full contact details
School of Biosciences
Firth Court
Western Bank
91Ö±²¥
S10 2TN
- Profile
-
I started my research career interested in metabolic enzyme structure and function and along the way I have turned my attention to increasingly more complex enzymes and proteins, especially those involved in nucleic acid transactions.
This has led me to question the foundations of our understanding of enzyme catalysis.
My research currently involves a series of collaborations aimed at exploring the evolution of enzyme mechanism via random mutagenesis of several enzymes and proteins.
A more recent interest has arisen through collaboration with the Microbiology community at 91Ö±²¥ and is the challenge of understanding the molecular basis of antibiotic resistance, in particular methicillin resistance.
Career history
- 2013 - 2015: Director of Innovation, Liverpool Life Sciences UTC
- 2012: Professor of Biochemistry Department of Molecular Biology and Biotechnology (on sabbatical leave at the Liverpool School of Tropical Medicine)
- 2007 - 2012: Head of the Department of Molecular Biology and Biotechnology
- 2008 - 2011: Director of Enterprise in Life Sciences
- 1999 - 2007: Professor of Biochemistry Department of Molecular Biology and Biotechnology
- 1999 - 2002: Director of the Transgenomic Research Laboratory
- 1998 - 1999: Reader Department of Molecular Biology and Biotechnology
- 1994 - 1998: Senior Lecturer Department of Molecular Biology and Biotechnology
- 1992 - 1993: Visiting Scientist Department Molecular Biology The Scripps Research Institute California
- 1990 - 1994: Lecturer Department of Molecular Biology and Biotechnology
- 1990: EMBO fellowship Gene Expression Program EMBL, Heidelberg
- 1986 - 1990: Lecturer Department of Biochemistry
- 1985 - 1986: Postdoctoral research associate Biozentrum der Universitat Basel, Switzerland
- 1984 - 1985: Postdoctoral research associate Departments of Biochemistry, 91Ö±²¥ and Genetics, Leeds
- 1980 - 1984: PhD (Biochemistry) University of 91Ö±²¥
- Research interests
-
DNA Modifying Enzymes: Cytosine-C5-specific DNA methyltransferases, in particular the monospecific enzyme, M.HhaI and the multi-specific enzyme M.SPRI. The aim is to identify essential residues involved in base flipping in the former and to determine the structural basis of multiple specificity in the latter.
RNA and DNA Polymerases present opportunities for developing a range of molecular biology methods and are in themselves key enzymes in cellular physiology. The former are of interest as targets for structure determination by new cryo-EM methods and the latter is a work horse for the development of in vitro mutagenesis methods in use in my lab.
Multi-enzyme complexes often contain components that are shared by other complexes. Using random mutagenesis methods, we are interested in the evolutionary pressures facing such promiscuous subunits, such as the E3 component of bacterial oxoacid dehydrogenases.
Enzymes are thought to bring substrates into precise alignment in order to stimulate product formation. Since many naturally occurring enzymes that catalyze the same reaction exhibit significant primary structural diversity, we are using random mutagenesis combined with screening and structural methods, to identify the sensitive and essential elements of primary structure in a range of enzyme catalyzed reactions and antibiotic resistance targets.
- Publications
-
Show: Featured publications All publications
Featured publications
Journal articles
All publications
Books
Journal articles
- . PLoS Pathogens, 16(7).
- . The Biochemist, 39(6), 51-51.
- . RNA, 21(3), 347-359.
- . Anal Biochem, 439(1), 47-49.
- . Molecules, 17(10), 12086-12101.
- . Molecules, 17(1), 796-808.
- . J Chromatogr A, 1216(9), 1377-1382.
- . RNA, 12(4), 691-696.
- . ANAL BIOCHEM, 350(1), 128-137.
- . J Biochem Biophys Methods, 58(1), 39-48.
- Identification of nuclear protein complexes using open tube capillary chromatography. AIChE Annual Meeting, Conference Proceedings, 1917.
- . Org Biomol Chem, 1(12), 2070-2074.
- . Nucleic Acids Res, 31(7), 1805-1812.
- . J Mol Biol, 326(5), 1389-1401.
- . J Bacteriol, 185(4), 1284-1288.
- . Eur J Biochem, 269(22), 5492-5501.
- . Anal Biochem, 309(2), 248-252.
- . Hum Mutat, 20(4), 305-311.
- . J Mol Biol, 321(4), 591-599.
- . J Biochem Mol Biol, 35(3), 348-351.
- . Anal Biochem, 304(1), 47-54.
- . Eur J Biochem, 269(5), 1525-1533.
- . Anal Biochem, 301(2), 290-297.
- . RNA, 8(2), 247-251.
- DNA replication with the mutagenic nucleotide dPTP; Effects of tautomerism on nucleotide incorporation. CHEMISTRY OF NUCLEIC ACID COMPONENTS, 5, 215-220.
- . Breast Cancer Res, 4(4), R6.
- Rapid analysis of biochemical modifications in DNA fragments - Visualisation of phosphorylation and cytosine deamination in single 15 minute analyses.. AM J HUM GENET, 69(4), 462-462.
- Rapid, high precision analysis of DNA and RNA footprinting reactions utilising the WAVE (R) Nucleic Acid Fragment Analysis System.. AM J HUM GENET, 69(4), 468-468.
- Novel mutations in the BRCA1 and BRCA2 gene in Iranian women with early-onset Breast Cancer. J MED GENET, 38, S54-S54.
- Analysis of nucleic acid modification enzyme reactions using IP RP HPLC. J MED GENET, 38, S71-S71.
- . Nucleic Acids Res, 29(7), 1565-1573.
- . Biochem Biophys Res Commun, 277(1), 147-151.
- . Nucleosides Nucleotides Nucleic Acids, 19(10-12), 1505-1516.
- . Anal Biochem, 284(1), 164-167.
- . Anal Biochem, 278(1), 46-51.
- Synthesis of two stable nitrogen analogues of S-adenosyl-L-methionine. J ORG CHEM, 64(20), 7467-7473.
- . Mycologist, 13(2), 96-IBC.
- . J Mol Biol, 286(2), 389-401.
- . Journal of Medical Internet Research, 1(SUPPL. 1).
- Studying the function of methyltransferases using nucleotide analogue based random mutagenesis. CHEMISTRY OF NUCLEIC ACID COMPONENTS, 2, 209-212.
- . Mol Hum Reprod, 4(12), 1136-1144.
- . Biochem Soc Trans, 26(4), S394.
- Novel splicing of ROMK K+ channel RNA generates new isoforms in rat kidney. JOURNAL OF PHYSIOLOGY-LONDON, 511P, 29P-29P.
- . Curr Opin Biotechnol, 9(4), 354-358.
- . J Physiol, 509 ( Pt 3), 629-634.
- Substitution of the conserved phenylalanine in the S-adenosyl-L-methionine binding site of M.MspI with tyrosine modifies the kinetic properties of the enzyme.. Biol Chem, 379(4-5), 591-594.
- The polypeptide backbone of recombinant human zona pellucida glycoprotein-3 initiates acrosomal exocytosis in human spermatozoa in vitro. BIOCHEM J, 330, 839-845.
- Quantification of ROMK mRNA expression in rat kidney by competitive polymerase chain reaction (PCR). JOURNAL OF PHYSIOLOGY-LONDON, 505P, 115P-115P.
- The polypeptide backbone of recombinant human ZP3 induces acrosomal exocytosis in human spermatozoa. HUM REPROD, 12(5), S13-S13.
- . Mol Hum Reprod, 2(12), 911-919.
- Renal and extrarenal localization of the RACTK1 K+ channel by immunofluorescence. JOURNAL OF PHYSIOLOGY-LONDON, 497P, P94-P95.
- Atomic force microscopy used to image the inwardly-rectifying ATP-sensitive potassium channel protein, ROMK1.. KIDNEY INTERNATIONAL, 50(5), 1780-1780.
- Renal and extrarenal localisation of the RACTK and ROMK1 K+-channel proteins. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 7(9), A0139-A0139.
- . Proc Natl Acad Sci U S A, 93(16), 8756-8760.
- . Mol Hum Reprod, 2(8), 583-589.
- Differential expression of ROMK1 and RACTK potassium channel mRNAs in cell lines. JOURNAL OF PHYSIOLOGY-LONDON, 493P, P92-P92.
- . J Mol Biol, 257(4), 804-813.
- A ROMK1/GLUTATHIONE-S-TRANSFERASE FUSION PROTEIN IMAGED USING THE ATOMIC-FORCE MICROSCOPE. JOURNAL OF PHYSIOLOGY-LONDON, 489P, P90-P90.
- IMMUNOCYTOCHEMICAL LOCATION OF THE POTASSIUM CHANNEL ROMK1 IN RAT-KIDNEY CORTEX. JOURNAL OF PHYSIOLOGY-LONDON, 489P, P93-P94.
- . Biochem J, 311 ( Pt 3), 901-904.
- . FEBS Lett, 355(1), 57-60.
- . Biochem J, 298 Pt 3, 727-732.
- . Biochem J, 298 ( Pt 1), 107-113.
- . J Mol Biol, 235(2), 545-553.
- . J Mol Endocrinol, 11(2), 191-200.
- . FEBS Letters, 323(3), 295-295.
- . Biochem J, 291 ( Pt 2), 493-504.
- . J Mol Biol, 230(3), 779-786.
- . Collection of Czechoslovak Chemical Communications, 58(s1), 116-119.
- . Methods Mol Biol, 16, 201-211.
- . Mol Microbiol, 6(21), 3251-3256.
- . Biochem J, 287 ( Pt 3), 871-879.
- . Methods Mol Biol, 11, 273-286.
- . FEBS Letters, 287(1-2), 226-227.
- S1 nuclease transcript mapping using sequenase-derived single-stranded probes.. Biotechniques, 10(4), 426-428.
- . Mol Microbiol, 5(3), 685-694.
- PURIFICATION, CHEMICAL MODIFICATION AND ANALYSIS OF PH-DEPENDENCE OF THE NADP+-DEPENDENT GLUTAMATE-DEHYDROGENASE OF ESCHERICHIA-COLI. BIOCHEM SOC T, 16(5), 876-877.
- . J Mol Biol, 200(1), 23-29.
- ISOLATION OF 3 COMPONENTS OF THE HYDROXYGLUTARATE PATHWAY FROM CLOSTRIDIUM-SYMBIOSUM. BIOCHEM SOC T, 15(6), 1039-1040.
- CHARACTERIZATION OF ECOP1 DNA ADENINE METHYLASE. BIOCHEM SOC T, 15(6), 1039-1039.
- . Nucleic Acids Res, 15(20), 8564.
- A SIMPLE METHOD FOR THE CALIBRATION OF RECORDING FLUOROMETERS BY KINETIC MEANS IN THE STUDY OF NAD(P)+-DEPENDENT DEHYDROGENASES. BIOCHEM SOC T, 15(3), 386-387.
- . Biochem J, 242(3), 789-795.
- . Gene, 54(2-3), 239-245.
- . J Mol Biol, 181(1), 147-149.
- . Int J Biochem, 17(7), 851-854.
- . Biochem J, 223(1), 161-168.
- . Eur J Biochem, 143(3), 557-560.
- . J Gen Microbiol, 130(9), 2385-2394.
- . Biochemical Society Transactions, 11(2), 175-176.
- . Int J Biochem, 15(4), 495-500.
- . ChemInform, 31(5), no-no.
Chapters
- , Restriction Endonucleases (pp. 1-18). Springer Berlin Heidelberg
- , Highly Selective Separations in Biotechnology (pp. 163-178). Springer Netherlands
- (pp. 185-197).
- Wiley-VCH Verlag GmbH & Co. KGaA
- John Wiley & Sons, Ltd
Conference proceedings papers
- Analysis of the RNA component of human telomerase and its associated activity.. AMERICAN JOURNAL OF HUMAN GENETICS, Vol. 71(4) (pp 333-333)
- A rapid, accurate and quantitative method for analysis of the methylation status of imprinted genes, using primer extension and IP RP HPLC.. EUROPEAN JOURNAL OF HUMAN GENETICS, Vol. 10 (pp 294-294)
- The signal transduction pathway of the acrosome reaction in human spermatozoa in response to purified recombinant human ZP3. HUMAN SPERM ACROSOME REACTION, Vol. 236 (pp 426-427)
- The production and purification of recombinant human ZP3 from E-6coli. HUMAN SPERM ACROSOME REACTION, Vol. 236 (pp 404-405)
- Induction of the human acrosome reaction by rhuZP3. HUMAN SPERM ACROSOME REACTION, Vol. 236 (pp 105-122)
- Teaching activities
-
Level 3 modules
- MBB308 Molecular Systems Biology and Synthetic Biology (Module Coordinator)
Level 2 modules
- FCP201 Molecules to Market (Module Coordinator)
- MBB267 Molecular Bioscience 2B
- Professional activities and memberships
-
- 2015 Fellow of the Royal Society of Biology (FRSB)
Links