Details of Award
NERC Reference : NER/T/S/2003/00724
Natural product screening on a chip-linking taxonomy to function.
Grant Award
- Principal Investigator:
- Professor AC Ward, Newcastle University, Sch of Biology
- Co-Investigator:
- Professor M Goodfellow, Newcastle University, Sch of Natural & Environmental Sciences
- Grant held at:
- Newcastle University, Sch of Biology
- Science Area:
- Marine
- Overall Classification:
- Marine
- ENRIs:
- Biodiversity
- Science Topics:
- Environmental Microbiology
- Environmental Genomics
- Systematics & Taxonomy
- Environmental biotechnology
- Abstract:
- This proposal is for a pilot project to test the phylogenetic distribution of secondary metabolite gene clusters in marine environments. Functional gene chips to test the distribution of a subset of natural product genes, including specific probes for known antibiotic genes, such as actinorhodin or the calcium dependent antibiotic of 'S. coelicolor', rapamycin or avermectin, and probes specific for gene classes such as poly-ketide synthetases will be designed and include probes to detect 16S genes. One of the limitations of functional gene chips is the inability to assign functional genes, detected in environmental or community surveys, to their host organism, except by inference from the phylogenetic analysis of the nucleic acid sequence of the functional gene itself. In this project, screening streptomycetes, the presence of, typically, 6 copies of the ribosomal rRNA gene cluster distributed around the genome will be used to link functional analysis with phytogenetic assignment. This is essential for secondary metabolite gene clusters in which the both the rate of evolution and the potential for lateral gene transfer mean that no inference can be made about the phylogeny of the organism from secondary metabolite sequence data. Large, fragments of genomic DNA will be isolated from environmental meta-genomes, cloned and screened for the presence of secondary metabolite and 16S genes. The 16S gene from such clones will be amplified and sequenced and the results correlated with the secondary metabolites detected. The project will test this strategy using about 500 deep-sea streptomycete isolates and two marine environmental metagenome libraries. This pilot project will provide a strategy for environmental sampling to test the distribution of secondary metabolite genes across phylogenetic, biogeographical and ecological niche - the limited success of historical search and discovery strategies for natural products to generate novel antibiotic in the last 30 years contrasts with the demonstration of extensive untapped microbial biodiversity and new search and discovery strategies are needed. The design of such strategies needs a much better understanding of how functional genes, in this case secondary metabolite biosynthesis genes, are distributed across that biodiversity and the environmental heterogeneity of the biosphere. At a fundamental level exactly the same questions need to be asked about other functional genes which contribute to the extensive eco-system services provided by microbes. This project proposes a proof a concept strategy for a gene chip approach to making such observations.
- NERC Reference:
- NER/T/S/2003/00724
- Grant Stage:
- Completed
- Scheme:
- Directed Pre FEC
- Grant Status:
- Closed
- Programme:
- Marine & Freshwater Microbial
This grant award has a total value of £30,209
FDAB - Financial Details (Award breakdown by headings)
| Total - Staff | Total - T&S | Total - Other Costs | Total - Indirect Costs |
|---|---|---|---|
| £8,335 | £615 | £17,425 | £3,834 |
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