My research career can be broadly summed up as an interest in global regulatory mechanisms that allow microorganisms to respond to the environment. My primary approach is usually genetic but once hypotheses have been generated I will use whatever techniques are approriate.
Induction of carotenoid biosynthesis in Myxococcus Xanthus . We have developed a model of the molecular basis of blue-light induction of gene expression in this bacterium. It involves a sigma factor, a membrane-bound light-sensitive anti-sigma factor; a repressor and a novel anti-repressor. Currently we have a grant to study the nature of the repressor/anti-repressor interaction and we are close to reconstructing the system in Escherichia coli . Control of primary and secondary metabolism in Streptomyces coelicolor A3(2). The Gram-positive Streptomyces are responsible for the production of 53% of all known antibiotics. I am the world expert on Streptomyces primary metabolism and have shown that anabolism is not regulated as in other bacteria. We have discovered a bifunctional enzyme with a role in tryptophan and histidine biosynthesis. We have also demonstrated that enzymes used in isoleucine/valine synthesis are also used in proline biosynthesis. This has provided important insights into enzyme evolution as well as a more complete understanding of streptomycete primary metabolism.
We currently have a SysMo grant to study the alternative mechanisms of anaplerosis in streptomycetes . Characterisation of novel pathogenicity determinants in the Gram-positive bacterium Listeria monocytogenes . Listeria monocytogenes is the causative agent of the deadly, food-borne disease listeriosis. I was able to identify generalised transduction in L. monocytogenes which allowed the identification of the molecular basis for the abortive infection mutant phenotype of Listeria monocytogenes. This discovery has implications for vaccine development and the understanding of the physiological basis of bacterial pathogenesis Molecular and cellular computing and synthetic biology. I have had long term collaborations with computer scientists to use DNA as a computing matrix (molecular computing) and to construct Boolean Nand gate logic circuits in gene expression pathways to carry out computation tasks (cellular computing). We also investigated the use of innate pattern formation properties of bacteria to carry out computations.
I gained a first class honours degree in Microbiology and Virology from the University of Warwick in 1976. I then moved to the Department of Genetics of the John Innes Institute where I gained a Ph.D. under the supervision of Dr. Keith Chater. For my research Ph.D. thesis I studied glucose repression in the genetically well characterised, Gram-positive bacterium Streptomyces coelicolor A3(2). I was able to demonstrate, using a number of 14C-labelled carbon sources, that their uptake and/or metabolism was repressed at the level of transcription by glucose. These studies allowed the isolation of mutants that no longer exhibited this control. Complementary studies on solid media led to the characterisation of several genes involved in the organism's ability to use agar as a carbon source. I received my degree in 1980 from the University of East Anglia (the J.I.I. is an affiliate Institute).
From February 1980 until July 1983 I was a postdoctoral fellow under the supervision of Dr. Lucy Shapiro of the Department of Molecular Biology of Albert Einstein College of Medicine, New York, U.S.A. Whilst in Dr. Shapiro's laboratory I participated in three projects involved in the study of Caulobacter crescentus (another bacterial model for development). 1) The mapping of mutations involved in membrane biogenesis which have demonstrated the linkage of membrane and DNA synthesis in this organism. Various double mutants were constructed and characterised. 2) We demonstrated that several proteins are phosphorylated in C. crescentus and one of these was phosphorylated to different extents throughout the cell cycle. We also demonstrated that a coliphage T7-like C. crescentus phage, fÖCdl, encodes a protein kinase, which may be involved in inactivating C. crescentus RNA polymerase. 3) We constructed and utilised a Tn5-based promoter probe for study of control of intermediary metabolism and differentiation in C. crescentus . It was whilst working on the latter project that I conceived of an integrative plasmid-based promoter probe. My period in Dr. Shapiro's laboratory gave me a solid grounding in Biochemical techniques and allowed me to extend my knowledge and practical experience in Bacterial Genetics.
On August 1st, 1983 I began work in Dr. Kaiser's Laboratory in the Department of Biochemistry, Stanford University, California. The work was funded by a grant from Life Science Research Foundation that was sponsored by Merck, Sharpe and Dohme Research Laboratories. At Stanford I gained extensive first hand experience in DNA cloning and manipulation techniques. Whilst there I developed a integrative plasmid-based promoter-probe for use in Myxococcus Xanthus . I also cloned a gene responsible for control of blue-light-inducible carotenoid production. I have continued to work on this system since I left California and took up my appointment at Warwick in October 1985.
- Bucca, Giselda, Pothi, Radhika, Hesketh, Andrew, Möller-Levet, Carla, Hodgson, David A, Laing, Emma E, Stewart, Graham R, Smith, Colin P, 2018. Translational control plays an important role in the adaptive heat-shock response of Streptomyces coelicolor. Nucleic Acids Research, 46 (11), pp. 5692-5703
- Wang, Ying, Penfold, Christopher A., Hodgson, D. A., Gifford, Miriam L., Burroughs, Nigel John, 2014. Correcting for link loss in causal network inference caused by regulator interference. Bioinformatics, 30 (19), pp. 2779-2786
- Iqbal, Mudassar, Mast, Yvonne, Amin, Rafat, Hodgson, D. A., Wohlleben, W., Burroughs, Nigel John, 2012. Extracting regulator activity profiles by integration of de novo motifs and expression data : characterizing key regulators of nutrient depletion responses in Streptomyces coelicolor. Nucleic Acids Research, Vol.40 (No.12), pp. 5227-5239
- Wentzel, Alexander, Bruheim, Per, Øverby, Anders, Jakobsen, Øyvind M, Sletta, Håvard, Omara, Walid A. M., Hodgson, D. A., Ellingsen, Trond E., 2012. Optimized submerged batch fermentation strategy for systems scale studies of metabolic switching in Streptomyces coelicolor A3(2). BMC Systems Biology, 6
- Waldvogel, Eva, Herbig, Alexander, Battke, Florian, Amin, Rafat, Nentwich, Merle, Nieselt, Kay, Ellingsen, Trond E., Wentzel, Alexander, Hodgson, D. A., Wohlleben, Wolfgang, Mast, Yvonne, 2011. The PII protein GlnK is a pleiotropic regulator for morphological differentiation and secondary metabolism in Streptomyces coelicolor. Applied Microbiology and Biotechnology, Vol.92 (No.6), pp. 1219-1236
Nieselt, Kay, Battke, Florian, Herbig, Alexander, Bruheim, Per, Wentzel, Alexander, Jakobsen, Øyvind M, Sletta, Håvard, Alam, Mohammad Tauqee, Merlo, Maria E., Moore, Jonathan, Omara, Walid A. M., Morrissey, Edward R., Juarez-Hermosillo, Miguel A, Rodríguez-García, Antonio, Nentwich, Merle, Thomas, Louise, Iqbal, Mudassar, Legaie, Roxane, Gaze, William H., Challis, Gregory L. et al (Select to open full list), 2010.
- Alam, Mohammad T., Merlo, Maria E., Hodgson, D. A., Wellington, E. M. H., Takano, Eriko, Breitling, Rainer, 2010. Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor. BMC Genomics, Vol.11 (No.202)
Nieselt, Kay, Battke, Florian, Herbig, Alexander, Bruheim, Per, Wentzel, Alexander, Jakobsen, Øyvind M., Sletta, Håvard, Alam, Mohammad T., Merlo, Maria E., Moore, Jonathan D., Omara, Walid A. M., Morrissey, Edward R., Juárez, Miguel A., Rodríguez-García, Antonio, Nentwich, Merle, Thomas, L., Iqbal, Mudassar, Legaie, Roxane, Gaze, William H., Challis, Gregory L. et al (Select to open full list), 2010.
- Barona-Gomez, Francisco, Hodgson, D. A., 2010. Multicopy proC in Streptomyces coelicolor A3(2) elicits a transient production of prodiginines, while proC deletion does not yield a proline auxotroph. Journal of Molecular Microbiology and Biotechnology, 19 (3), pp. 152-158
- Saqi, Mansoor, Dobson, Richard J B, Kraben, Preben, Hodgson, D. A., Wild, David L., 2009. An approach to pathway reconstruction using whole genome metabolic models and sensitive sequence searching. Journal of Integrative Bioinformatics, Vol.6 (No.1)
- Wright, H. (Helena), Noda-Garcia, Lianet, Ochoa-Leyva, Adrian, Hodgson, D. A., Fülöp, Vilmos, Barona-Gomez, Francisco, 2008. The structure/function relationship of a dual-substrate (beta alpha)(8)-isomerase. Biochemical and Biophysical Research Communications, 365 (1), pp. 16-21
- Whitworth, David E., Millard, Andrew D., Hodgson, D. A., Hawkins, Peter F., 2008. Protein-protein interactions between two-component system transmitter and receiver domains of Myxococcus xanthus. Proteomics, Vol.8 (No.9), pp. 1839-1842
- Whitworth, David E., Holmes, Antony B., Irvine, Alistair G., Hodgson, D. A., Scanlan, David J., 2008. Phosphate acquisition components of the Myxococcus xanthus Pho regulon are regulated by both phosphate availability and development. Journal of Bacteriology, 190 (6), pp. 1997-2003
- Amos, Martyn, Hodgson, D. A., Gibbons, Alan (Alan M.), 2007. Bacterial self-organisation and computation. International Journal of Unconventional Computing, 3 (3), pp. 199-210
- Pham, Vinh D., Shebelut, Conrad W., Jose, Ivy R., Hodgson, D. A., Whitworth, David E., Singer, Mitchell, 2006. The response regulator PhoP4 is required for late developmental events in Myxococcus xanthus. Microbiology, Vol.152 (Part 6), pp. 1609-1620
- Battke, F., Herbig, A., Wentzel, A., Jakobsen, Ø. M., Bonin, M., Hodgson, D. A., Wohlleben, W., Ellingsen, T. E., Nieselt, K., 2011. A Technical Platform for Generating Reproducible Expression Data from Streptomyces coelicolor Batch Cultivations. In Arabnia, H.R; Tran, Q-N. (eds.), Software Tools and Algorithms for Biological Systems, New York, Springer, pp. 3-15
- Amos, Martyn, Gibbons, Alan (Alan M.), Hodgson, D. A., 1996. Error-resistant implementation of DNA computations. University of Warwick. Department of Computer Science
|Title||Funder||Award start||Award end|
|Exploiting microbial genomics and synthetic biology for discovery of novel antibiotics||BBSRC||01 Sep 2013||30 Sep 2016|
|TRAIN-ASAP 2011||European Commission||01 Jan 2012||19 Sep 2016|
|Global Metabolic Switching in Streptomyces Coelicolor.||BBSRC||01 Dec 2006||17 Nov 2011|
|The Myxococcus xanthus Pho regulon: functional characterisation of a complex system with multiple regulatory components.||BBSRC||01 Oct 2005||30 Sep 2008|
|Light-regulated Gene Expression in Myxococcus Xanthus: The Mechanism of Action of Anti-repressor CarS on Repressor CarA||BBSRC||01 Jan 2007||21 Sep 2008|
|Light-regulated gene expression in Myxococcus xanthus: the mechanism of action of anti-repressor CarS on repressor CarA||BBSRC||01 Jan 2004||31 Dec 2006|
|A whole genome analysis of two-component system signal transduction pathways in myxococcus xanthus||BBSRC||22 May 2005||15 Sep 2005|
|A whole genome analysis of two-component system signal transduction pathways in Myxococcus xanthus||BBSRC||01 Apr 2002||22 May 2005|
|Vacation Studentship for Sanjeev Kumar||BBSRC||12 Jul 2004||03 Sep 2004|
|Vacation Studentship for Lucy Pylypiw||Society for General Microbiology||05 Jul 2004||27 Aug 2004|
|Royal Society Travel Grant||Royal Society||01 Jul 2003||30 Jul 2003|