Biography

My first degree, in Microbiology, was obtained from the University of Bristol in 1981.
From 1981-1984 I undertook my PhD studies on molecular genetics of Streptomyces in the labs of Prof Keith Chater and Prof Sir David Hopwood at the John Innes Institute, Norwich. My research was focussed on developing RNA methods for Streptomyces and characterisation of gene structure and regulation - using the glycerol catabolic operon as a model system.

I moved back to the University of Bristol (Biochemistry Department) in 1985 to work as a postdoctoral research associate in the lab of Professor Nigel Brown, continuing to dissect regulatory mechanisms controlling the glycerol operon. I took up a Lectureship in Molecular Genetics at UMIST (Manchester) in 1988 and for the next 10 years studied a range of regulatory systems in Streptomyces, most notably the heat-shock response.

From 1999 I started to embrace multidisciplinarity - engaging in collaborative research projects with chemists, mathematicians, engineers, statisticians and computer scientists. From 2001-2002 I undertook a sabbatical in the Control Systems Centre (Dept. Electronics and Electrical Engineering) at UMIST with Dr Olaf Wolkenhauer. Since then my major research areas have been biosynthetic engineering on nonribosomal peptide antibiotics, DNA microarray technology, global analysis of gene expression and characterization of transcriptional regulatory networks.

For the last 10 years I have managed a BBSRC/EC funded microarray/bioinformatics resource at Surrey (formerly at Manchester), principally for the international Streptomyces community. I moved to the University of Surrey in 2003 to take up the new Chair of Functional Genomics, My major areas of research currently revolve around systems level analysis of Streptomyces regulatory networks and of human sleep physiology in the context of global gene expression (monitored from leukocytes).

Research Interests

    A. Systems biology of Streptomyces coelicolor

Our current activities cover two broad inter-related areas:

1. Transcriptional regulatory networks controlling morphological and ‘physiological’ differentiation (e.g. antibiotic production). We are in the process of constructing transcription factor regulatory networks by using a combination of global gene expression profiling and ChIP-on-chip analysis approaches. We have developed experimentally-validated high density arrays (44,000 x 60 mer and 105,000 x 60 mer formats) for this work. In addition to examining the global distribution of RNA polymerase we are currently investigating several transcription factors, including PhoP, CdaR, AbsA2 and DasR (in collaboration with Gilles van Wezel at Leiden University, NL) and AtrA (in collaboration with Kenny McDowall at Leeds University, UK).

2. Non-coding RNA and the primary transcriptome of Streptomyces coelicolor. In recent years it has become clear that small non-coding RNAs play a diverse role in the control of cellular processes in bacteria. We have used our 105K arrays to identify large numbers of small intergenic non coding RNAs, some of which are implicated in controlling morphology and antibiotic production. We are now switching to applying ‘RNA-seq’ to build a comprehensive picture of all non-coding RNAs under a variety of liquid and surface-grown conditions. It is envisaged that the findings of this study will be integrated with the data on transcription factor regulatory networks and that both will ultimately be integrated with the genome scale metabolic network.

Current collaborators:

Internal: Emma Laing, Andrjez Kierzek, Mike Bushell, Claudio Avignone-Rossa

External: Gilles van Wezel (Leiden), David Hodgson (Warwick), Mark Paget (Sussex), Klas Flärdh (Lund) and Kenny McDowall

Current funding from the BBSRC

On-line research resources

We have developed a number of on-line tools for microarray data analysis, genomics and metabolic pathway analysis. Microarrays and a variety of software tools and data resources are available from our website.

    B. Systems level analysis of human sleep physiology

The generic nature of high throughput techniques such as gene expression profiling has led us to develop multidisciplinary collaborations with other groups within FHMS. We are working with Prof Derk-Jan Dijk and others in the Surrey Sleep Research Centre on two major inter-related research contracts:

1. Circadian and homeostatic contributions to physiology, cognition and
genome-wide expression in human and mouse variants of the PER3 VNTR
polymorphism [BBSRC funded since 2008]

2. Cognitive vulnerability following extended wakefulness in defined genotypes:
Effects of sleep duration on sustained attention, executive function, and
novel biomarkers [AFOSR (USA) funded since 2008].

Current collaborators

Derk-Jan Dijk, Simon Archer, Malcolm von Schantz, John Groeger (Cork)

C. Global analysis of gene expression in tumours following chemotherapy. Collaboration with Professor N. Karanjia (Royal Surrey County Hospital), supported by the Liver Cancer Surgery Appeal since 2007.

D. Vitamin D fortification, vitamin D status and global gene expression in leukocytes

A new BBSRC-funded collaboration with Drs Sue Lanham-New and Kath Hart within FHMS: Ergocalciferol (D2) vs. Cholecalciferol (D3) Food Fortification: Comparative Efficiency in Raising 25OHD Status & Mechanisms of Action (D2-D3 Study) [Funded from 2011]

Publications

Teaching

Undergraduate

Molecular Biology and Genetics – Level 1 (Module co-ordinator)

Molecular Biology and Genetics – Level 2

Molecular Biology and Genetics – Level 3

Microbiology Systems – Level 2

Postgraduate

MSc Medical Microbiology (MMIM018) Module: Microbial Genetics and Molecular biology

Departmental Duties

Faculty Research Strategy Leader for Systems Biology

Academic lead: Core Microarray Facility

Member: Faculty Research Committee

Resources

DNA microarray resource

For information on availability of DNA microarrays and their use please access: The Streptomyces coelicolor Microrray Resource