Biological applications



Identifying new genetic and molecular targets to improve bioenergy crops

Rothamsted Research: Dr Angela Karp, Dr Steve Hanley

Renewable energy has been identified by the UK Government as a vital part of the wider sustainability agenda. This presents a formidable challenge and contributions from several renewable energy sources will need to be significantly boosted. Biomass has been identified as playing a significant role in this increase. Willows are among the most advanced biomass crops in temperate regions. The project aims to integrate in-house genetic and genomic willow resources (genetic maps, QTLs, ESTs) with publicly available data sets from model organisms (e.g. Arabidopsis, poplar) to begin the transition from willow QTLs to specific candidate genes for further study, with the ultimate aim of direct selection of beneficial alleles within the crop improvement pipeline.

Functional candidate genes that are implicated in key architecture and yield-related traits will be first identified from model organisms such as Arabidopsis and poplar using data integration and deep text mining techniques. In parallel, by running an Ondex workflow, available willow EST and genomic sequence previously generated at Rothamsted will be annotated by sequence comparison with publicly available databases. Sequence homology will then be used to identify willow orthologues of functional candidates identified from the willow genomic datasets. As a final stage, candidate gene sets that combine both positional and functional information for further study will be generated.



Integration augmentation and validation of yeast metabolome models

University of Manchester: Prof Douglas Kell
VIDEO of our ISMB 2009 technology track demo

Yeast is an important model organism for both its practical uses in fermentation and its genetic similarities to higher, more complex eukaryotes. Yeast is a single-celled eukaryotic organism which is widely used as a simple model for cell biology in humans and the study of human metabolic disease, because its internal signalling pathways are similar to those in human cells.

The project proposes to use the combined technologies of Ondex, data integration, Taverna, text mining and graph analysis to study the yeast metabolome and its response to different conditions. This will enable an increased understanding of yeast metabolism and also identify common metabolic processes for modelling in yeast and other systems.



Supporting research into the role of telomere function in ageing

University of Newcastle, CISBAN (Centre for Integrated Systems Biology of Ageing and Nutrition):
Prof David Lydall, Prof Anil Wipat

Dividing cells balance the conflicting needs of maintaining genetic stability with those of replicating and segregating their genomes. Double strand breaks (DSBs) in DNA are particularly dangerous to genetic stability. Accordingly, DSBs are potent activators of cell cycle arrest and DNA repair. Telomeres look very much like DSBs, yet in most normal cells they are "capped" and hence hidden from repair and cell cycle arrest (checkpoint) pathways. However, as fibroblasts age, telomeres become uncapped, DSB-like, and stimulate repair and checkpoint pathways.

This project in budding yeast, Saccharomyces cerevisiae, examines the interactions of repair and checkpoint pathways with uncapped telomeres. It uses some of the powerful approaches available only in budding yeast to study how the DDR (DNA damage response) responds to uncapped telomeres. Firstly, the system will be customised to incorporate the latest S. cerevisiae data sources, together with information gathered as part of the CISBAN project, and used, together with the literature extracted through text mining to review telomere biology in S. cerevisiae, to further understand how pathological responses to uncapped telomeres are regulated by DNA repair and checkpoint pathways and the identification of novel genes and interactions that occur.


Biofortifying Brassica with calcium (Ca) and magnesium (Mg) for human health

University of Nottingham: Prof Martin Broadley, Dr Niel Graham
University of Warwick: Dr John Hammond
Rothamsted Research: Prof Chris Rawlings, Dr Artem Lysenko, Dr Sue Welham, Mr Pierre Carion

Many UK adults consume insufficient calcium (Ca) or magnesium (Mg) for adequate health. Dietary Ca and Mg could be increased through crop biofortification. We recently identified for the first time, wide natural genetic variation, substantial heritability, and individual loci affecting leaf Ca and Mg concentration (leaf-Ca and Mg) in plants. We have an immediate and timely opportunity to resolve these loci and to understand their regulation for use in biofortification strategies using vegetable Brassica. The aim of this project is to characterise genes and gene networks regulating leaf-Ca and Mg using: (1) genomic sequence, new microarrays and mapping populations of Brassica for comparative and genetical genomics (eQTL); (2) novel TILLING (Targeting Induced Local Lesions IN Genomes) mutants of Brassica to test gene function in planta, using novel eQTL-targets and locus-specific paralogues of Type IA CAX cation transporters known to affect leaf Ca homeostasis in Arabidopsis. All data will curated in the public domain (via www.brassica.info) to enable marker-assisted selection for use in pre-breeding pipelines. We will use novel and existing gene targets to define regulatory gene networks controlling leaf-Ca and Mg using database integration (Ondex) and modelling techniques (Petri Net) under development in our laboratories. We will define genes, alleles, and their regulatory network architecture in the context of increasing industry-use of calcium nitrate (Ca(NO3)2) fertiliser. Ca(NO3)2 can improve Brassica crop quality, reduce greenhouse gas emissions, and improve the security of fertiliser storage.