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Personal profile

Scholarly biography

Genomics has been at the heart of Colin Smith’s research for the last 20 years encompassing a range of interdisciplinary collaborations, investigating antibiotic production by bacteria, human sleep and human nutrition. His first degree, in Microbiology, was undertaken at the University of Bristol and his PhD was awarded for research at the John Innes Centre (Norwich, UK) where he studied the regulation of gene expression in antibiotic producing bacteria. He is presently focusing on regulation of stress responses in Streptomyces bacteria and how antibiotic production by these bacteria is controlled at the level of translation. He is also investigating how vitamin D influences human gene expression by measuring gene activity in the blood of healthy participants. He is currently a member of the Centre for Stress and Age-Related Disease (STRAND) and the Centre for Regenerative Medicine and Devices (CRMD).

He joined the University of Brighton in 2016 to establish Brighton Genomics and to integrate genomics approaches in new interdisciplinary collaborations across Brighton’s research institutions and collaborations with other UK universities. He is a strong advocate of personal genomics and data sharing and had his whole genome sequenced in 2013. Colin is the first person to have donated his genome sequence under ‘open consent’ to the Personal Genome Project UK.

Colin was the lead organiser of a recent Royal Society international scientific meeting: Changing views of translation: from ribosome profiling to high resolution imaging of single molecules in vivo’. This meeting brought together leading researchers from across the world who study gene expression at two ends of the spectrum – from global analysis of translation of all genes in cells and tissues to analysis of expression of single molecules using new high resolution imaging techniques.

Supervisory Interests

My research interests are largely focussed around the study of gene regulation, using a variety of genomics approaches - particularly those techniques for studying the transcriptome and the 'translatome'. Current research areas for MRes and PhD research projects include the identification of RNA-binding proteins in Streptomyces and their role in translational control following exposure to environmental stresses, such as heat-shock and cold-shock. Translational control of anitbiotic production is also a key research topic for postgraduate research. More broadly, I am also currently investigating the influence of chronic illness on human gene expression and of vitamin D supplementation on the whole human blood transcriptome.

Research interests

Stress responses and translational control of antibiotic production by Streptomyces bacteria

We are presently focussing on understanding how Streptomyces bacteria respond to environmental stress at the level of gene expression and how they control the gene clusters that encode production of so-called ‘secondary metabolites’, which include the majority of antibiotics in clinical use since the 1940s. We are exploiting genomics technologies within Brighton Genomics to understand, at a global level, how the biological systems are regulated, both at the level of transcription and translation.

The main aim of this research project is to understand how key genes are controlled at the level of translation in this complex group of soil bacteria. To date most studies of gene expression have focussed on studying transcription, the production of mRNAs. However, a new technique called ‘ribosome profiling’ (Ribo-seq) enables us to measure the level of translation of all mRNAs. This gives us a very different picture of gene expression and, importantly, reveals that the control of gene expression at the level of translation is far more widespread than we realised. Our goal is to determine the molecular processes which orchestrate this control by identifying the RNA-binding proteins and RNA molecules which co-ordinate the regulation. We currently know very little about how these processes operate in bacteria.

We also collaborate with GlaxosmithKline (UK) on the translational control of commercially important natrual products.

Research interests

Role of 'cold-shock' proteins in the regulation of translation in the G+C-rich Streptomyces bacteria.

It has recently been discovered from studies on the model bacterium, Escherichia coli, that ‘cold-shock’ proteins (CSPs), a universally conserved protein family, fulfil important roles in regulating messenger RNA secondary structure after the organism has been subjected to low temperatures. CSPs bind the mRNA to facilitate its unfolding, making it available for translation by ribosomes. We have recently revealed that translation of the homologous CSP family Streptomyces bacteria is enhanced following exposure to heat-shock. We hypothesise that the CSPs in Streptomyces, which are highly abundant proteinshave evolved to fulfil an essential function at all temperatures to maintain mRNAs in a translatable state; this is because the high %G+C content of the streptomycete genes (typically >80% G+C in protein coding ORFs) generates considerable secondary structure in the encoded mRNAs, hindering the ability of ribosomes to translate them.

This interdisciplinary project brings together complementary expertise in genetic manipulation and genome wide analysis of translation in Streptomyces, cutting-edge mass spectrometry-based proteomics (Nicolas Stewart, Brighton) and cutting-edge in vitro array-based screening of transcription and translation (Anastasia Callaghan, Portsmouth) to understand the role of CSPs in Streptomyces and to exploit this information to modulate gene expression in synthetic biology platforms, both in vivo and in vitro. The outputs of this research project could find applications in industrial biotechnology and in in vitro synthetic biology platforms.

Research interests

Exploiting genomics to understand the role of vitamin D in human health and metabolism

Vitamin D is essential to human health. It is crucial for bone and muscle health and it is important for protection against many diseases, including hypertension, infection, autoimmune diseases, diabetes and cancer. Vitamin D deficiency is widespread among the population and is a major public health concern in the UK and many other countries worldwide. Vitamin D3 (cholecalciferol) is the natural form that is made by our skin when exposed to ultraviolet B (UVB) radiation in sunlight and obtained from some animal-derived foods, while plant/fungus-derived vitamin D2 (ergocalciferol) is obtainable from supplements and some artificially fortified foods and is generally manufactured by UV-irradiating mushrooms. At the latitude of the UK there is only sufficient UVB radiation from sunlight between the months of April and September and therefore it is recommended that we take vitamin D3 supplements between October and March. The UK new government guidelines are that we take 10 micrograms vitamin D per day as a supplement.

Our over-arching aim is to understand how vitamin D supplementation influences gene expression and consequently health in humans. To do this we analyse genome-wide expression in whole human blood across time following vitamin D supplementation. We are currently undertaking this study with healthy white European and South Asian women, the latter to explore whether there may be ethnic differences in the response to elevated levels of vitamin D in the body. We are investigating the global influence of the two different forms of vitamin D,  D2 and D3 on the transcriptome, as part of a randomised placebo-controlled trial. Vitamin D2 is generally used by vegans, vegetarians and Muslims since it is not derived from animal products. 

This work was supported by DRINC, a partnership between BBSRC, the Engineering and Physical Sciences Research Council (EPSRC), the Economic and Social Research Council (ESRC), the Medical Research Council (MRC), and a consortium of leading food and drink companies. Continuation of this research has been made possible by generous donations from the University of Brighton and by Michael and Maureen Chowen.

Latest findings

Vitamin D3 was found to be significantly better at raising serum total 25-hydroxyvitamin D (25(OH)D) levels than vitamin D2; 25(OH)D is used as a measure of how efficiently vitamin D is assimilated in the body. The results from our genomic analysis are surprising. Strikingly, we have discovered that in many cases the two forms of vitamin D influence expression of different cellular pathways (judged from whole blood transcriptome analysis), where vitamin D3 influences many more genes than D2. This raises the intriguing possibility that vitamin D2 may not be exerting the same biological effects in humans. The interpretation and further validation of these findings is ongoing. Ultimately, the results of our study are likely to have a high societal and economic impact because they may influence future national and international guidelines on the fortification of foods with vitamin D2.

 

 

Keywords

  • R Medicine (General)
  • Microbiology
  • Genomics

Fingerprint Dive into the research topics where Colin Smith is active. These topic labels come from the works of this person. Together they form a unique fingerprint.

  • 1 Similar Profiles
Streptomyces coelicolor Medicine & Life Sciences
Regulon Medicine & Life Sciences
Genome Medicine & Life Sciences
Ergocalciferols Medicine & Life Sciences
Cholecalciferol Medicine & Life Sciences
Transcriptome Medicine & Life Sciences
Anti-Bacterial Agents Medicine & Life Sciences
Genes Medicine & Life Sciences

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Research Output 2014 2019

Genome-wide analysis of the role of the antibiotic biosynthesis regulator AbsA2 in Streptomyces coelicolor A3(2)

Lewis, R., Wahab, A., Bucca, G., Laing, E. E., Moller-Levet, C., Kierzek, A. & Smith, C., 10 Apr 2019, In : PLoS ONE. 14, 4, p. 1-23 23 p., e0200673.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File
Streptomyces coelicolor
antibiotics
biosynthesis
Genome
Anti-Bacterial Agents

Stress hormone-mediated acceleration of breast cancer metastasis is halted by inhibition of nitric oxide synthase

Flaherty, R. L., Intabli, H., Falcinelli, M., Bucca, G., Hesketh, A., Patel, B., Allen, M., Smith, C. & Flint, M., 24 May 2019, In : Cancer Letters. 459, p. 59-71 13 p.

Research output: Contribution to journalArticleResearchpeer-review

Nitric Oxide Synthase
Hormones
Breast Neoplasms
Neoplasm Metastasis
Glucocorticoids

Personal Genome Project UK (PGP-UK): a research and citizen science hybrid project in support of personalized medicine

Personal Genome Project UK (PGP UK) & Smith, C., 27 Nov 2018, In : BMC Medical Genomics. 11, 12 p., 108.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File
Precision Medicine
Genome
Research
Genomics
Information Dissemination

Translational control plays an important role in the adaptive heat-shock response of Streptomyces coelicolor

Bucca, G., Pothi, R., Hesketh, A., Moller-Levet, C., Hodgson, D. A., Laing, E. E., Stewart, G. R. & Smith, C., 9 May 2018, In : Nucleic Acids Research. 46, 11, p. 5692–5703

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File
Streptomyces coelicolor
Heat-Shock Response
Polyribosomes
Hot Temperature
Molecular Chaperones

Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial

Tripkovic, L., Wilson, L., Hart, K., Johnsen, S., de Lusignan, S., Smith, C., Bucca, G., Penson, S., Chope, G. & Elliott, R., 5 Jul 2017, In : American Journal of Clinical Nutrition. 106, 2, p. 481-490 10 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File
Ergocalciferols
Cholecalciferol
Placebos
Food
Vitamin D