Biomedical Sciences Research Institute

Centre for Functional Genomics

    Centre for Functional Genomics

    Introduction

    The Centre of Excellence in Functional Genomics was established on 1st October 2003, in the University of Ulster at Coleraine, with £2m funding from the European Union (EU) Programme for Peace and Reconciliation, under Technology Support for the Knowledge-Based Economy.

    JPEG - 38.3 kb
    Giant model of the DNA double helix - photo A Hermida

    Project Aims and Objectives

    The project aims to augment the existing world-class biotechnology and biomedical facilities at Coleraine by creating a specialist Centre of Excellence in Functional Genomics (CFG), which concentrates on research projects that may, in the short or long-term, have commercial impact on biotechnology, biomedicine or high-added-value food production. This is being carried out using the modern techniques of functional genomics - the molecular analysis of how gene products work, as opposed to structural genomics - the discovery of what genes exist. The CFG is intended to give rise to spin-off companies from the University, which will take advantage of novel ideas and technologies and also attract inward investment into Northern Ireland: immediately and directly into the adjacent University of Ulster Science Park; more indirectly, by stimulating the environment in which high-technology, high information content, high added value components can be incorporated into existing commercial enterprises.

    Management of the Centre for Functional Genomics Project

    The CFG Project is managed by a Principal Investigator (Profesor Stephen Downes) who is assisted by a management board comprising the leaders of Research Groups involved in the project, meeting at monthly intervals to discuss strategy for the CFG and the CMB building in which it is embedded.

    Equipment Purchased to Assist CFG Research Projects A portion of the CFG grant has been used to purchase equipment such as a microarray reader, real-time PCR machine, two mass spectrometers, protein purification workstation and PALM laser microdissection system, all of which are installed and functioning. Five cell culture laboratories are now up and running.

    Research Areas The principal research themes are:
    - Creation of probiotic or prebiotic enhancers of functional foods
    - Optimisation of next-generation antibiotics
    - Exploitation of the genomic diversity of extremophilic micro-organisms
    - Cloning and exploitation of amphibian and other peptides with biological activity
    - Creation of transgenic mice for analytical purposes
    - Use of gene transfer to enhance tumour therapy
    - Stem cell differentiation to islet cell phenotypes for diabetes using stable and novel peptides targeting islet cells
    - Transfection of milk-borne maternal gene transcripts to the mammalian neonate

    Staff have already been recruited to work in these areas of research. Below is a brief summary of these research projects.

    Stem cell differentiation to islet cell phenotypes for diabetes using stable and novel peptides targeting islet cells (Professor Peter Flatt, Professor Finbarr O’Harte) This project will continue the exploitation of novel amphibian peptides pioneered by our Pharmaceutical Biotechnology Research Group. Seventeen such peptides have been identified as having potent activities on insulin-secreting pancreatic islet cells; all have been sequenced and can be synthesised in a pure form, removing the need for further isolation from venom. The proposal is to develop their use further and to seek to discover conditions that will allow stem cell differentiation into glucose-responsive islet cells, which may ultimately prove a potent therapy for diabetes.

    Transfection of milk-borne maternal gene transcripts to the mammalian neonate (Dr Tony Bjourson) This project is also derived, less directly, from the previous work of our Pharmaceutical Biotechnology Research Group, who demonstrated that some amphibian skin venom peptides can bind to and stabilise messenger RNAs; this may be a means of ensuring that venom-affected tissues are subverted into continuing to synthesise fresh venom components, thus producing a long-lasting toxic effect. Dr Bjourson, who was part of the team that established this, has produced the imaginative hypothesis that milk, which is also a skin secretion, may also contain mRNA-stabilising peptides. If so, the consequences for our understanding of neonatal health and the proper formulation of infant feeds may be very considerable.

    Validation of probiotic or prebiotic enhancers of functional foods It is obviously desirable to make high added-value products wherever possible. In the case of the food industry, value can be added by modifying products so that they are not only nutritious, but contribute to health; thus creating functional foods. One way of doing this is to incorporate ingredients that modify the bowel bacteria so as to reduce the risk of disease: either desirable bacteria (probiotics) or substrates that encourage desirable bacteria (prebiotics). However, in this case there is little evidence that functional foods, even if they do modify the bowel flora, really act on bowel cells so as to reduce the risk of disease. We therefore intend to develop genomic technology that will allow us to monitor from human nucleic acids in faecal samples, the response of human colon cells to functional foods.

    Exploitation of the genomic diversity of extremophilic micro-organisms (Professor Geoff McMullan) Extremophile micro-organisms, capable of flourishing in conditions that destroy most forms of life, are a barely-tapped biological resource; many of them are only distantly related to more normal micro-organisms. We are concentrating on the use of Geobacillus as a source of small biologically active proteins that inhibit the growth of other micro-organisms; and on the investigation of the functional genomic diversity of a number of Geobacillus isolates. We intend thus to identify proteins and the genes that encode them, of application in the pharmaceutical and biotechnology industry.

    Optimisation of next generation antibiotics (Dr James Dooley) Dr Colm Lowery, after being recruited to work on this project has since taken up a post of Lecturer in Medical Microbiology at UU in Coleraine. He is continuing to work on this project in collaboration with the Centre for Disease Control in Atlanta and Belfast City Hospital and is concentrating on the development of a real-time PCR-based method for the rapid detection of pathogens in various samples (water, food, shellfish, human). The PALM laser micro-dissection system, mentioned above, will prove optimal for excising Cryptospridium from cell culture at various stages in its developmental cycle.

    Exploitation of amphibian and other peptides with biological activity (Professor Peter Flatt) The intention of this project is to investigate novel peptides from amphibian secretions and to modify peptides of known biological activity so as to give them desirable properties (increased resistance to degradation, preferential uptake by target tissues) so as to develop therapeutically useful compounds. Several novel peptides from amphibian venom and modified forms of peptides involved in glucose metabolism have been shown to have considerable biological activity.

    Creation of transgenic mice for analytical purposes (Professor Stephen Downes) The participants in this project intend to develop transgenic mice that will serve to identify the tissue-specific and mechanism-specific actions of mutagenic carcinogens; these should have commercial applications. The researchers then intend to supplement this by creating other transgenic strains, which will be deficient in the repair of mutagenic damage; crosses between the two strains should be more useful. With funding from a CEC grant, the University has already made progress in the supplementary part of this project: mice that it is believed will be hypersensitive to low levels of radiation have been produced and are viable. Their radio-sensitivity is yet to be determined.