Biological Sciences

Profile

Geoff graduated in 1972 with a BSc (Hons) degree in Biophysics from the University of Leeds. He stayed in the Astbury dept. of Biophysics to do his PhD on X-ray crystallographic analysis of biological molecules, which he was awarded in 1975.

He took up his first post-doctoral post in the Biophysics Laboratories of what was then Portsmouth Polytechnic, where he stayed from 1975 to 1979. In this time, his research was the on structure of chromatin, principally using the technique of neutron scattering, which involved frequent visits to the Institut Laue-Langevin in Grenoble.

This was followed by postdoctoral positions at the European Molecular Biology Laboratory, Heidelberg (1979-1983), where he carried out studies of viral DNA binding proteins using a wide range of biochemical and biophysical techniques. Geoff subsequently moved to the Department of Chemistry, University of Cambridge (1983-1985) where he carried out research on the structure of oligonucleotide duplexes, especially those containing base pair mismatches, using the technique of X-ray crystallography.

In 1985, Geoff returned to Portsmouth as a Senior Lecturer, and was subsequently promoted to Principal Lecturer. In 1990, he was one of the first in the country to be awarded a prestigious Leverhulme Trust Senior Research Fellowship by the Royal Society. In 1992, he was made a Reader and in 1994, was appointed to a Chair in Biomolecular Science. Since 1999, he has been Director of the Institute of Biomedical and Biomolecular Sciences, and in 2002 was also appointed as Associate Dean (Research) in the Science Faculty.

Current and Past Lab members

External Committees

College 8 (Biology) sub-committee of Institut Laue-Langevin, Grenoble, France (2006-2008)

External Examining

• External examiner for Medical and Veterinary Sciences Tripos, Cambridge University, 2010 - 2013
• External examiner for BSc Biochemistry/Molecular Biology, Liverpool University (2006-2009)
• External examiner for BSc Molecular and Cellular Biochemistry at Oxford University
• External examiner for BSc Biological Chemistry at Leicester University.
• External examiner for MSc Molecular Biotechnology at University of Leicester
• External examiner for MSc Molecular Biotechnology at University of Nottingham
• External examiner for PhD theses at Universities of Exeter, Cambridge, Sheffield, Dundee, East Anglia, Birmingham, Southampton, Bristol, Oxford, Nottingham, Newcastle, Glasgow, York

Research Interests

Geoff's research interests continue to be in the application of biochemical, biophysical and molecular biological techniques to the study of protein-nucleic acids. In addition to the cloning, expression, purification and site-directed mutagenesis of DNA binding proteins, techniques include gel retardation analysis, DNA footprinting, fluorescence spectroscopy, CD, analytical centrifugation, light scattering, X-ray crystallography, neutron scattering, NMR and surface plasmon resonance.

Current Research Projects:

• The single stranded DNA binding protein (gene 5 protein) of Fd bacteriophage, its interaction with novel G-quartet containing nucleic acid structures and its role in prion capture.
• Characterisation and structural analysis of Type I DNA methyltranferases, and related multisubunit enzymes.
• Structure and function of the controller protein that regulates the temporal expression of restriction/modification genes
• Structural and functional domains of the origin binding protein UL9 of the virus HSV-1
• Nuclear receptors and co-repressors : protein-protein and protein-DNA interactions

Recent Publications

More recent publications

Publications Before 2008

• Papapanagiotou I, Streeter S.D., Cary, P.D. and Kneale G.G. (2007) DNA structural deformations in the interaction of the controller protein C.AhdI with its operator sequence. Nucleic Acids Research 35, 2643-50
• Yuan J, Xiao X, McGeehan J, Dong Z, Cali I, Fujioka H, Kong Q, Kneale G, Gambetti P, Zou WQ. (2006) Insoluble Aggregates and Protease-resistant Conformers of Prion Protein in Uninfected Human Brains. J. Biol. Chem. 281, 34848-58.
• Friedeberg,C., Scarlett, G., McGeehan, J., Abu-daya, A., Guille, M. and Kneale, G. (2006). Identification of a structural and functional domain in xNAP1 involved in protein-protein interactions. Nucleic Acids Research 24, 4893-9
• McGeehan, J.E., Papapanagiotou I, Streeter S.D. and Kneale G.G. (2006) Cooperative Binding of the C.AhdI Controller Protein to the C/R Promoter and its Role in Endonuclease Gene Expression. J. Mol. Biol. 358, 523-31
• McGeehan, J. E., Streeter, S., Papapanagiotou, I., Fox, G.C. and Kneale G.G. (2005) High-resolution crystal structure of the restriction-modification controller protein C.AhdI from Aeromonas hydrophilia. J. Mol. Biol. 346, 689-701
• Chant A, Kraemer-Pecore CM, Watkin R, Kneale GG. (2005) Attachment of a histidine tag to the minimal zinc finger protein of the Aspergillus nidulans gene regulatory protein AreA causes a conformational change at the DNA-binding site. Protein Expression and Purification 39, 152-159.
• Yuan, J, Kinter, M., John McGeehan, J. E., Perry, G., Kneale, G. G. , Gambetti,P., and Zou, W-Z. (2005) Concealment of epitope by reduction and alkylation in prion protein. Biochem. Biophys. Res. Comm. 326, 652-659
• Streeter, S.D., Papapanagiotou, I., McGeehan, J.E. & Kneale, G. G. (2004) DNA footprinting and biophysical characterisation of the controller protein C.AhdI suggests the basis of a genetic switch. Nucleic Acids Research 32, 6445-53
• Scarlett GP, Elgar SJ, Cary PD, Noble AM, Orford RL, Kneale GG, Guille MJ. (2004) Intact RNA binding domains are necessary for structure specific DNA binding and transcription control by CBTF122 during Xenopus development. J. Biol. Chem. 279, 52447-55
• McGeehan, J. E., Streeter, S., Cooper, J.B., Mohammed, F., Fox, G.C and Kneale, G.G. (2004) Crystallization and preliminary X-ray analysis of the controller protein C.AhdI from Aeromonas hydrophilia. Acta Crystallographica Section D, 60, 323-325.
• Marks, P., McGeehan, J.E. and Kneale, G.G. (2004) A novel strategy for the expression and purification of the DNA methyltransferase, M.AhdI. Protein Expression and Purification 37, 236-242
• Chant, A. Provatopoulou, X., Manfield I. and Kneale G.G. (2003) Structural and functional characterisation of the DNA binding domain of the A. nidulans gene regulatory protein AreA. Biochimica Biophysica Acta 1648, 84-89.
• Marks, P., McGeehan, J., Wilson, G., Errington, N. and Kneale, G.G. (2003). Purification and Characterisation of a Novel DNA Methyltransferase, M.AhdI. Nucleic Acids Research 31, 2803-2810.
• Smith, M., Read, C.M. and Kneale, G.G. (2001) "Domain structure and subunit interactions in the type I DNA methyltransferase M.EcoR124I" J. Mol. Biol. 314, 41-50
• Oliver, A.W., Bogdarina, I., Schroeder, E, Taylor, I.A. and Kneale, G.G. (2000) Preferential binding of fd gene 5 protein to tetraplex nucleic acid structures. J. Mol. Biol. 301, 575 - 584

Recent Research Grants

A total of £5.6m of external research funding has been awarded to date, most recently:

• BBSRC: £445,031 awarded for "DNA Distortion, Sequence Recognition and the Control of R-M Gene Expression". PI, with 1 co-applicant ( Dr J McGeehan). 2010-2013
• Wellcome Trust: £200,000. Structural biology of type I restriction-modification enzymes (2006-2009)
• BBSRC £485,000. Structural analysis of the genetic switch controlling expression of the AhdI restriction-modification system (2006-2009)
• EPSRC £800,000. (Renewal) Deuteration Initiative for Biological Neutron Scattering and NMR (co-applicant, with 6 other Universities) 2006-2009
• Wellcome Trust £157,000. Structure and function of the methyltransferase M.AhdI. 2003-2006
• BBSRC. £200,000. The structural basis of gene regulation in a novel restriction-modification system. 2003-2006
• EPSRC £780,000. Deuteration Initiative for Biological Neutron Scattering and NMR (co-applicant, with 6 other Universities) 2002-2005
• Wellcome Trust (JREI): £780,000 awarded for "A 600 MHz facility for biomolecular research". (1999-2004). PI with 2 co-applicants
• Wellcome Trust: £143,000 awarded for “Structure-specific DNA and RNA sequence recognition by the Fd gene 5 protein” (1997-2000)
• BBSRC: £163,572 awarded for “Structure-function relationships of a novel, developmentally regulated CCAAT box transcription factor” for 3 years Co-applicant with Dr M.J. Guille (1996 - 1999).
• BBSRC: £169,000 awarded for “Structure and interactions of the Gene Regulatory Protein AreA of Aspergillus Nidulans” for 3 years (1995 - 1999)
• Wellcome Trust: £124,000 awarded for “Structural studies of the Methyltransferase M.EcoR124I and its interaction with DNA” for 3 years (1995 - 1999)