The University of Southampton
Biological Sciences
Phone:
(023) 8059 4374
Email:
K.R.Fox@soton.ac.uk

Professor Keith R Fox MA, MPhil, PhD

Professor of Biochemistry, Principal Investigator (Nucleic Acids), Associate Director of the Faraday Institute for Science and Religion, Cambridge

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Professor Keith R Fox is Professor of Biochemistry within the Centre for Biological Sciences at the University of Southampton

Career history

2000-present: Professor of Biochemistry. University of Southampton, UK.
2012-2013: Acting Head of Centre for Biological Sciences
1994-2000: Reader, Division of Biochemistry & Molecular Biology, School of Biological Sciences, University of Southampton.
1992-1994: Senior lecturer, Department of Physiology & Pharmacology, University of Southampton.
1989-1994: Lister Institute Research Fellow.
1987-1991: Lecturer, Department of Physiology & Pharmacology, University of Southampton.
1982-1986: Research Fellow, Emmanuel College, Cambridge.
1980-1986: Research Associate, Department of Pharmacology, University of Cambridge.

Academic qualifications

PhD (Pharmacology). University of Cambridge, UK.
MPhil (Pharmacology). University of Cambridge, UK.
MA Natural Sciences (Biochemistry). University of Cambridge, UK.

Research

Publications

Teaching

Contributions

Contact

Research interests

My research concerns the sequence specific recognition of DNA by small molecules, oligonucleotides and proteins, and the formation of unusual DNA structures (triplexes and quadruplexes). Compounds that bind to DNA in a sequence specific fashion have potential for artificially controlling gene expression and may be used as anticancer or antiviral agents. Several DNA binding antibiotics are currently used in cancer chemotherapy, and we are seeking to understand the molecular mechanisms by which they bind to DNA with a view to designing new agents with improved selectivity. In all our studies we make extensive use of the footprinting technique, using both natural and synthetic DNA fragments, and have developed this assay as a powerful tool for measuring the specificity, stability and kinetics of ligand-DNA interactions. This has been used to determine the sequence selectivity of several DNA-binding small molecules.

For the past 15 years my work has focussed on triple helix formation as a means for targeting specific DNA sequences. Together with Professor Tom Brown (Chemistry) I have developed several nucleotide analogues, which are designed to form stable triplexes under physiological conditions. Using a combination of these we demonstrated the first example of four base-pair recognition of a DNA sequence by a triplex-forming oligonucleotide at pH 7. In order to facilitate our studies on the stability of triplexes, quadruplexes and small-molecule-DNA complexes we developed a high throughput fluorescence assay for determining DNA melting profiles.

DNA quadruplexes can be formed by G-rich DNA sequences, and these may play a role in telomere structure or controlling gene expression. We have studied their biophysical properties studies, examining their stability, structure, and competition with DNA duplexes.

Together with Professor Tom Brown (now in Chemistry, Oxford) we have developed a novel fluorescence assay for measuring the stability of DNA duplexes, triplexes and quadruplexes [Darby et al. (2002) High throughput measurement of duplex, triplex and quadruplex melting curves using molecular beacons and the LightCycler. Nucleic Acids Res. 29, e39]. This uses synthetic oligonucleotides to which are attached a fluorophore (fluorescein) and a quencher (methyl red). These are positioned so that these groups are close together in a folded DNA structure, such as a quadruplex or duplex, thereby quenching the fluorescence. On increasing the temperature the DNA melts, separating these fluorescence groups and there is a large increase in fluorescence. These experiments are performed on the Roche LightCycler, allowing us to examine 32 samples in parallel, using only small volumes (20 µL) of dilute oligonucleotides (0.25 µM).

Current MPhil/PhD students:

Mohammad Basher:
Interaction of novel pyrrolobenzodiazepines (PBDs) with DNA
Commonwealth Academic Staff Scholarship

Mohammed Alsulami:
Structure and properties of “sticky DNA” formed by GAA repeats.
Saudi Arabia Scholarship

Ibrahim Sayoh:
DNA recognition by Triple helix formation
Thai Government Scholarship

James Edwards:
Mutants of Uracil DNA Glycosylase for Detecting Modified Cytosine
Mayflower Studentship from the University of Southampton

Research group(s)

Molecular and Cellular Biosciences

Affiliate research group(s)

Institute for Life Sciences (IfLS)

Research project(s)

DNA sequence recognition by triple helix formation

One means of achieving precise DNA sequence recognition over several base pairs involves the formation of intermolecular DNA triple helices.

DNA quadruplexes and their interaction with ligands

We are studying the structure of DNA quadruplexes in linear and supercoiled DNA and are examining their effects on gene expression when they are located in promoters.

DNA sequence recognition by small molecules

We are using the footprinting technique with natural and synthetic DNA substrates to study the sequence selectivity of novel DNA binding small molecules.

Modifying nucleic acid nanostructures by triplex formation

We are exploiting the formation of DNA triplexes as a means for generating new DNA nanostructures.

Modifying Uracil DNA Glycosylase

We are generating mutants of this DNA repair enzyme, which have altered recognition properties, and are using these as tools in biotechnological applications.

Extending the boundaries of nucleic acid chemistry

We are part of this BBSRC-funded sLoLa project, led by Prof Tom Brown (Chemistry), and are using click-chemistry to generate unusual DNA structures and examine their biological properties.

Article(s)

Book(s)

  • DNA conjugates and sensors - Fox, Keith R. and Brown, Tom (eds.)
    Published:
    2012
    Published by:
    London, GB
    Series:
    Biomolecular Science Series
    Pages:
    316pp
  • Drug-DNA interaction protocols - Fox, Keith R. (ed.)
    Published:
    2010
    Published by:
    New York, US
    Series:
    Methods in Molecular Biology, 613
    Pages:
    311pp

Book Section(s)

Module coordinator

BIOL2017 Pharmacology B
BIOL3027 Selective Toxicity

Contributor

BIOL2010 Molecular and Cellular Biochemistry: The flow of genetic information
BIOL2016 Pharmacology A
BIOL3013 Molecular Recognition

Professional Contributions

Associate Director of the Faraday Institute for Science and Religion, Cambridge
Senior Executive Editor. Nucleic Acids Research
Former Chair. Christians in Science
Editor. Science & Christian Belief

Professional Memberships

American Chemical Society
British Biophysical Society
Biochemical Society
Fellow of the Royal Society of Chemistry
Member of the Lister Institute of Preventive Medicine

Professor Keith R Fox
Centre for Biological Sciences Faculty of Natural & Environmental Sciences Life Sciences Building 85 University of Southampton Highfield Campus Southampton SO17 1BJ

Room Number: 85/4053

Telephone: (023) 8059 4374
Email: K.R.Fox@soton.ac.uk

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