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About the Research Theme |
  
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Description of the ThemeThe era of automated DNA sequencing and genome databases (genomics) has arrived and with it have come new methods for identifying particular genes and their protein products (proteomics). It is the expression of a set of genes in a particular cell type which defines the function of that cell. The pattern of gene expression can change, for example during development, or as a result of mutation or disease, so that analysis of altered expression profiles provides fundamental information on basic biological processes. However, understanding how such changes come about requires knowledge of factors that control gene expression as well as the functions of the individual protein products. Assigning function to an unknown protein depends on knowing its precise composition and 3-dimensional structure, as well as its interaction partner. Functional proteomics leads in turn to a deeper understanding of physiological processes. Such genome to proteome studies rely on some sophisticated technology - most of which is now in place on this campus, or soon will be - that can be applied to the study of any tissue or organism. The equipment includes a gene microarray facility, laser capture microscope, LC-mass spectrometer and limited X-ray diffraction equipment, all of which have received support from the University. Underpinning the operations is the use of advanced methods in computational biology (bioinformatics). A number of proven investigators are embracing these new technologies with the common goal of understanding or manipulating gene expression. In addition to using common methodologies, members of this theme share a similar intellectual approach to the analysis of genes and proteins, irrespective of the great diversity of organisms under study. Membership and current projectsPrincipal Departments and Staff Involved:Anatomy & Structural BiologyGreen, Williams BiochemistryBroom, Brown, Carne, Cutfield, Day, Dearden, Eaton-Rye, Farnden, Guilford, Hughes, Lamont, Ledgerwood, Legge, Macknight, Marshall, McCormick, Merriman, Poulter, Reeve, Stockwell, Tate, Thompson, Wilbanks BotanyBurritt, Summerfield Microbiology & ImmunologyFineran, Ronson Oral Sciences and OrthodonticsMonk PathologyBraithwaite, Eccles, Horsfield, Markie, Morison, Robertson, Royds PhysiologyMcDonald Current projects:BraithwaiteWe are interested in how the p53 tumour suppressor decides whether to cause cells to stop growing or to die. Our data derive from studying the functional outcomes of interactions between p53 and other proteins. In most cases we study proteins which bind p53 from the DNA tumour viruses SV40, adenovirus, and papilloma virus. We are also studying the transcriptional control of the p53 gene. BrownBioinformatics and Translational Control
BurrittThe plant biotechnology programme of Dr Burritt in the Botany department focuses on the application of plant tissue and cell culture technologies to agriculture and horticulture. Areas of emphasis are, at present, (i) the physiology of lettuce plants grown in aeroponic culture and (ii) the role light quality plays in controlling the growth and development of crop plants in vitro. These studies involve investigations of specific genes and their protein products. Cancer Genetics Laboratory (Reeve, Guilford, Eccles, Morison)The long-term goal of the Cancer Genetics Laboratory is to provide clinical information and technologies which will help the cancer patient. This research group is now one of the largest and most successful in NZ. Their programme involves basic biomedical research through to clinical studies and they are recognised as international experts in their field. Specific investigations include: determining the early genetic changes in the onset of childhood leukemia, finding the genetic basis of heritable stomach cancer, determining the molecular basis for the metastatic behaviour of colorectal cancer, and identifying the role of developmental genes in kidney cancer. CarneVision research: Research is focussed in two areas (i) molecular-level analysis (involving cDNA cloning and proteomics) of components of the visual signal transduction pathway using an invertebrate (squid) retinal model, to contribute to knowledge of the structure and function of the transducisome signalling complex in vision, and (ii) comparative analysis of the protein complement, using proteomics, of glaucomatous and non-glaucomatous aqueous humour to identify proteins as candidates for involvement in glaucoma, to contribute to molecular-level knowledge of this presentation affecting 2% of the population over 40 years in New Zealand (collaboration with Assoc. Prof. A. Molteno, Otago). CutfieldOur work is aimed at explaining the biological activities of proteins in terms of their 3-dimensional structures. This allows us to design novel (mutant) proteins with modified properties and also inhibitor molecules that could serve as lead compounds for drug development. Currently we are working with enzymes from pathogenic microorganisms, including Candida albicans, Glomerella cingulata and Pseudomonas aeruginosa. A proteomics approach to these organisms would allow us to evaluate other protein targets for structure-based drug design. DayApoptosis is an evolutionarily conserved process required for normal development of multicellular organisms.Ê In mammals the biochemical steps that signal for apoptosis are complex and depend on the death stimulus.Ê Although a number of proteins have been shown to have important roles in regulating apoptosis the molecular details of how they function are poorly understood. Research in my laboratory is primarily aimed at characterisation of the biochemical properties of a number of proteins with important roles in regulating cell death.Ê In particular, we are currentlyÊ focused on characterisation of complexes formed between numerous proteins and both the Bcl-2 family proteins and the IAP family of proteins.Ê We use a combination of structural biology, mutagenesis experiments and interaction assays to investigate complex formation. DeardenResearch in my laboratory is focussed on the study of molecular and developmental evolution. One main theme of the research is the study of the evolution of developmental pathways. We aim to understand the molecular events underlying evolutionary changes in animal morphology, particularly the evolution of segmentation mechanisms in animals. The laboratory studies a number of non-model arthropod species, including spider-mites, brine-shrimps, Drosophila, Bees and Onychophora. Another major theme of our research is the study of horizontal gene transfer. We are trying to understand the effect of horizontal gene transfer from transgenic crops to the environment, and its role in genome evolution. Eaton-RyeMy research group is exploring structure/function relationships of critical proteins required for successful water-splitting in photosynthesis and the unique phosphoryl group transfer reactions that are found in two-component signal transduction. Our experimental system is the cyanobacterium Synechocystis sp. PCC 6803. The complete genomic sequence of this organism is available and we utilise this information for the design of experiments that address gene expression and targeted mutagenesis. FarndenThe work of this group focuses on the control of gene expression in plants. Various projects are being undertaken to identify the regulatory sequences in the promoters of several plant genes involved in nitrogen and carbon metabolism or in the establishment of the legume-Rhizobium symbiosis. It is hoped this work will lead to the identification of elements that can be used to control and target the expression of agriculturally and horticulturally useful plant genes. Specifically we are examining the post-harvest, sucrose regulated expression of genes in asparagus; the identification and expression of amylase genes in apple; and the repression of the plant asparaginase gene in nodulated legumes. Fineran My research group in interested in two related areas, specifically microbial gene regulation and interactions between bacteria and their phage. We use Serratia to examine networks of regulatory mechanisms that enable this bacterium to control the production of extracellular virulence factors, undergo swarming and produce both carbapenem and prodigiosin antibiotics. Our current research uses global approaches (e.g. genomics) in addition to traditional genetic and biochemical techniques to continue to unravel novel mechanisms of gene regulation using this ‘model’ bacterium. My laboratory also examines interactions between bacteria and phages, in particular of mechanisms of phage resistance in Gram-negative bacteria. GreenGlobal gene expression profiling of small cell numbers using Serial Analysis of Gene Expression (SAGE). Design and use of cell-targeted DNA microarrays. High throughput bioinformatics analysis of gene expression profiles. Horsfield In the Chromosome Structure and Development Group (www.otago.ac.nz/csdg), we are interested in how proteins needed for sister chromatid cohesion during mitosis can also contribute to gene expression, animal development and cancer. The main focus of our research is exploring alternative roles for these proteins, particularly in controlling the transcription of developmental genes. Our aim is to investigate developmental pathways that operate downstream of chromatid cohesion proteins using a vertebrate model: the zebrafish. Since there is high conservation of developmental genes throughout evolution, we will be able to use the information from our zebrafish model to interpret developmental roles chromatid cohesion proteins might play in mammals and humans. Hughes Research in the Neural Development and Disease Lab is aimed at identifying molecular pathways regulating neuronal development and disease. Current research is focused on the zinc finger transcription factors of the forebrain embryonic zinc finger family. These transcription factors are required for patterning and differentiation of specific neurons in the cortex, olfactory bulb and hypothalamus. The function of these transcription factors is being investigated using affinity purification of protein complexes containing transcription factors as well as lentiviral-mediated misexpression and knockdown to analyse the genes regulated by these proteins. LamontOur research focusses on the mechanisms that enable a pathogenic bacterium, Pseudomonas aeruginosa, to cause disease. We are using genomic and proteomic approaches to dissect out this process and to better understand the processes that control expression of genes that contribute to infection. As well as enhancing understanding of fundamental cellular processes, this research will reveal potential targets for new anti-Pseudomonas drugs. Ledgerwood The work in the laboratory is aimed at understanding the role of redox changes in mammalian cellular processes such as apoptosis, gene expression and protein folding. We are also investigating a novel cytochrome c variant identified in a NZ family. We use a combination of cell biological and protein biochemistry techniques in our research. LeggeMy research programme is investigating pre-implantation embryo development relating to metabolic and genetic interactions of the oocyte and embryo with its environment. Related to this I am also involved in investigations relating to non-enzymatic reactions in biomedical solutions, including tissue culture media. MacknightThe focus of this programme is to understand the processes of plant development (specifically the control of flowering) using molecular genetic techniques and the model plant Arabidopsis thaliana.
MarkieThe laboratory has an interest in the functional analysis of genes implicated in the development of colorectal cancer, including the genes implicated in rare polyposis disorders, the DNA mismatch repair genes and the mitotic spindle checkpoint genes. We are currently involved in mutation screens in cancers, in the development of yeast complementation systems for biological assays of functional human variants, and in yeast two-hybrid searches for interacting protein partners. MarshallLiving things are found from -80°C in the Antarctic to 120°C in "black smokers" in the depths of the oceans. How do the proteins that are critical for life cope with such a wide range of temperatures? Our work seeks to determine the specific molecular changes in proteins that allow organisms to functionally normally at low temperatures. McCormickStructural and Functional Analysis of the Protein Interactions Involved in Lipoprotein(a) Assembly
McDonaldOverall aim of understanding how the epithelial sodium channel, which is required to maintain normal salt and fluid balance and blood pressure, is controlled. Identification and analysis of proteins that interact with, and potentially regulate, the epithelial sodium channel. A number of proteins in the ubiquitination pathway have been shown to interact with and regulate the epithelial sodium channel's activity. Identification of proteins involved in the trafficking of the epithelial sodium channel to and from the plasma membrane. MerrimanDefining pathways of type 1 diabetes: A multifaceted approach is being used to identify genes and proteins involved in the pathway of type 1 diabetes development. In human, the human genome project is enabling the discovery of functional candidate genes which are tested for association with disease. In mouse, pancreatic proteomes are compared between diabetes prone and resistant strains to discover proteins specific to the diabetes process. PoulterRetrotransposons are probably present in all eukaryotes (fungi, plants and animals). They are often abundant representing about 50% of the maize genome for example. Retrotransposons are highly mobile and therefore the exact pattern of retrotransposon integration sites in the genome is strain specific. This makes the retrotransposon pattern (as displayed by PCR or other techniques) a strain specific 'fingerprint'. Such fingerprints can be used in PVR classification. They can also be used for strain recognition in fungal pathogens of plants (such as Magnaporthe grisea the rice blast fungus). RobertsonCongenital Malformations in Children: The prime thrust of my research is the identification of the genetic determinants of congenital malformations in children. This work has resulted in our recent identification of a new gene family, encoding proteins called filamins, that is involved in the development of a broad range of structural abnormalities in children. Ongoing work is aimed at identifying how filamins operate within the cell to cause these problems as well as identifying other genes that lead to anomalies in much the same way that filamin genes do. Our laboratory attracts referrals of patient samples from around the globe for genetic analysis. RonsonMolecular genetics, genomics and ecology of the Rhizobium-legume symbiosis. The nucleotide sequence of the 500-kb symbiosis island of Mesorhizobium loti has just been completed, and the focus is now on uncovering the function of all identified genes, using microarray, proteomic and mutational analyses. Analysis of role of gene transfer in the evolution and environmental adaptation of soil microbes; molecular genetics and ecology of rhizosphere colonisation. RoydsThe focus of my laboratory is on the prognostic, mechanistic and therapeutic significance of p53 and other tumour suppressor genes (TSG) in human solid tumours. Current studies include work on the relationship between p53 status and genetic/telomeric instability in CNS tumours in which we have shown that Alternative Lengthening of Telomeres (ALT) confers a favourable prognosis in patients with gliomas. We are also determining the clinical significance of interactions between p53 and the new potential oncogene YB-1. Work is in progress on the development of therapeutic strategies for combating cancer based on TSG dysfunction, with special emphasis on viro-oncology. StockwellSince completing a PhD on the computer simulation of genetic drift and sequence analysis by computer, work has focussed on the growing area of bioinformatics. Aside from managing and programming on Unix computer systems and advising others on their use and on the interpretation of results, effort is directed to importing and evaluating public domain applications software for genomic work. I have extensive experience and interest in computer analysis and manipulation of genome and sequence data, in particular the development of widely-distributed software for multiple sequences with particular capabilities for phylogenetic analysis, routines for the automated parsing of sequence database entries and in the automatic derivation of downstream data from them. Summerfield Cyanobacteria are a diverse phylum of photosynthetic microbes with potential applications in bioremediation; bioenergy production; biofertilisation, and in the identification of novel bioactive compounds. My research interests include the application of molecular techniques to examine the diversity and metabolic flexibility of cyanobacteria. This work combines the use of model strains, for which high throughput genomics approaches are available, alongside screening for novel New Zealand cyanobacterial strains. TateThe research group has a major focus on gene expression and how it is regulated at the translational level. It introduced a Bioinformatics component to the research 10 years ago by establishing a database TransTerm to characterise the translational stop signal. Genomics is important to the research group since full genome sequences provide the resources to extend the characterisation of the stop signal from bacteria to humans. This has led to novel strategies for drug design to treat AIDS, to understanding mechanisms of synthesising selenoproteins, and how one signal can be used for selenium incorporation and for stopping the synthesis. The research group now has a major interest in structural genomics to determine how the translational stop signal is decoded by specific proteins, a feature unique among the decoding mechanisms used in protein biosynthesis, and how the signal recognition is transmitted to promote the release of the completed polypeptides. ThompsonThe focus of my research is on hormonal and nutrient regulation of the expression of a number of newly-discovered genes (uncoupling proteins and leptin) that are involved in regulating energy balance. Identification of factors that regulate these genes will give important insights into how body weight is regulated in health and disease. WilbanksMolecular chaperones control the structure, location and longevity of other proteins. Regulation of these properties of mature gene products has as profound an effect on biological activity as does regulation of gene expression. Dr Wilbanks's group focuses on the structures of the chaperones themselves and how they grasp their partners. Research subjects include the "trigger factor" chaperone of Mycobacterium tuberculosis and Haemophilus influenzae and the WT1 tumor suppressor protein implicated in the pediatric Wilms' tumor. WilliamsA major goal of our research group is to understand how memories are laid down in the brain. Specifically we aim to uncover molecular changes that occur at the synapse which may contribute to memory processes. In these studies we use traditional biochemical techniques and electron microscopy along side state-of-the-art functional genomics including DNA microarray technology and proteomics. These studies are carried out within the Department of Anatomy & Structural Biology in close collaboration with research teams within the Departments of Biochemistry andÊ Psychology. CollaborationsInternationalCSIRO, Canberra, Australia
NationalHort Research (4 Projects)
ObjectivesThe overall objective of the theme is to promote, foster and enhance research in the areas of Functional Genomics, Gene Expression and Proteomics within the University, and both nationally and internationally. To achieve this it is planned to:
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