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Genomic And Proteomic Dissection Of The Molecular Basis Of Kidney Development.
Funder
National Health and Medical Research Council
Funding Amount
$454,582.00
Summary
The number of nephrons present in the human adult kidney can vary by threefold. This is likely to be due to slight variations in the rate of nephron formation during development. Evidence is mounting that a reduced number of nephrons can predispose to renal failure later in life in response to stresses such as hypertension or substance abuse. 80,000 new cases of end stage renal failure occur each year in the US, with 25% of these related to hypertension and therefore possibly linked to a low nep ....The number of nephrons present in the human adult kidney can vary by threefold. This is likely to be due to slight variations in the rate of nephron formation during development. Evidence is mounting that a reduced number of nephrons can predispose to renal failure later in life in response to stresses such as hypertension or substance abuse. 80,000 new cases of end stage renal failure occur each year in the US, with 25% of these related to hypertension and therefore possibly linked to a low nephron number. While it is known that the kidney arises through a series of reciprocal inductive events between the metanephric mesenchyme and the ureteric bud, a better understanding of the molecular basis of these events is needed to understand what dictates nephron endowment. The Wilms tumour suppressor protein WT1 is not only mutated in some cases of the childhood kidney cancer, Wilms tumour, but is also critical for the normal development of the metanephros, as demonstrated by knockout experiments in mice. One of the earliest genes expressed in the metanephric mesenchyme, WT1 is thought to prevent this tissue from dying before differentiation, directing it to form the kidney and, postnatally, regulating normal podocyte function. Although known to be a nuclear regulatory protein, the genes directly regulated by WT1 have not been clearly or convincingly delineated. This study aims to directly screen for changes to gene expression and protein production levels induced by WT1. To do so, an array approach unique in its use of a specific array set derived from developing kidney will be used. In concert, additional specific clone sets derived from mouse kidney prior and post the commencement of nephron formation will be constructed and analysed. As WT1 is a nuclear protein involved in splicing, this study will involve a parallel investigation at a proteomic level of changes in spliceosomal proteins in response to changes in WT1.Read moreRead less
The Role Of Transcriptional Co-activators And Co-repressors During Embryonic Development
Funder
National Health and Medical Research Council
Funding Amount
$82,421.00
Summary
Every creature starts out as a single fertilized egg. The genome directs the embryonic development of the egg by regulating the expression of genes each of which must be turned on or off at the correct time and place. This essential balance between the activation or repression of genes is controlled by groups of proteins, including ‘transcriptional co-activators’ and ‘repressors’. This project aims to better understand the role of these proteins during embryonic development.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347245
Funder
Australian Research Council
Funding Amount
$630,000.00
Summary
Functional Genomics Analysis - linking a multicentred facility. The aim of this project is to enhance and network the functions and activities of the Clive and Vera Ramaciotti Centre for Gene Function Analysis (CGRCGFA), a joint venture that services five major universities in the Sydney-Newcastle area. This application is for equipment that will improve the speed of DNA analyses, and for a laboratory information management system that will standardise the handling of data and sample information ....Functional Genomics Analysis - linking a multicentred facility. The aim of this project is to enhance and network the functions and activities of the Clive and Vera Ramaciotti Centre for Gene Function Analysis (CGRCGFA), a joint venture that services five major universities in the Sydney-Newcastle area. This application is for equipment that will improve the speed of DNA analyses, and for a laboratory information management system that will standardise the handling of data and sample information at all nodes of the CVRCGFA.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0232455
Funder
Australian Research Council
Funding Amount
$545,000.00
Summary
The Molecular Analysis of Variation and Gene Function. The aim of this project is to establish the nodes of the Clive and Vera Ramaciotti Centre for Gene Function Analysis (CVRCGFA) which is a joint venture that serves the five major universities and three Institutes in the Sydney-Newcastle region. The primary focus of this application is to create new facilities at the hubs of CVRCFGA that are integral to the analysis of molecular variation in a range of organisms. The study of molecular vari ....The Molecular Analysis of Variation and Gene Function. The aim of this project is to establish the nodes of the Clive and Vera Ramaciotti Centre for Gene Function Analysis (CVRCGFA) which is a joint venture that serves the five major universities and three Institutes in the Sydney-Newcastle region. The primary focus of this application is to create new facilities at the hubs of CVRCFGA that are integral to the analysis of molecular variation in a range of organisms. The study of molecular variation will enable researchers to understand better how organisms interact with each other, how they respond to environmental stress and aid in the identification of complez traits.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453724
Funder
Australian Research Council
Funding Amount
$532,824.00
Summary
Functional Genomics - Linking Genomics and Proteomics. This application is to enhance the capacity of the Ramaciotti Centre for Gene Function Analaysis (RCFGA) and its Nodes to support research in Functional Genomics by expanding its ability to link genomic analysis (including transcriptomics) with proteomic and cell biological analysis. It will provide access to novel methods for analysing interactions of proteins with other molecules by enabling the manufacture of protein arrays as well as DN ....Functional Genomics - Linking Genomics and Proteomics. This application is to enhance the capacity of the Ramaciotti Centre for Gene Function Analaysis (RCFGA) and its Nodes to support research in Functional Genomics by expanding its ability to link genomic analysis (including transcriptomics) with proteomic and cell biological analysis. It will provide access to novel methods for analysing interactions of proteins with other molecules by enabling the manufacture of protein arrays as well as DNA microarrays and to analyse the data obtained from them. This is a vital component to maintain gene function analysis at the cutting edge of current technology.Read moreRead less
Use of Gradipore technology to develop novel methods for the preparation and segregation of mammalian spermatozoa. The purpose of this project is to harness the expertise available within an Australian biotechnology company, Gradipore, to develop novel methods for the preparation of mammalian spermatozoa and the segregation of these cells into X-and Y- bearing populations. This technology will find application in: (1)clinical andrology, where rapid, safe protocols for the preparation and segrega ....Use of Gradipore technology to develop novel methods for the preparation and segregation of mammalian spermatozoa. The purpose of this project is to harness the expertise available within an Australian biotechnology company, Gradipore, to develop novel methods for the preparation of mammalian spermatozoa and the segregation of these cells into X-and Y- bearing populations. This technology will find application in: (1)clinical andrology, where rapid, safe protocols for the preparation and segregation of human spermatozoa are being actively sought in the context of assisted conception and the management of sex-linked genetic diseases and (2) agriculture, particularly the cattle industry, where a capacity to predetermine the sex of the offspring would be extremely valuable.Read moreRead less
I am a developmental biologist who identifies and characterises genes required for normal embryonic development in mouse. I translate this information into the genetic diagnosis and developmental understanding of congenital malformations in humans.
Mouse models for the identification of factors involved in muscle adaptation. The ability of muscle to adapt to meet functional demands is essential for mobility in normal daily life, in ageing well, in individuals with muscle diseases and nerve damage and in athletes. The ability of muscle to change its cellular composition is desirable for the livestock industry. Knowledge of how genes in muscle cells are regulated to adapt to demands has significant implications for public health and economic ....Mouse models for the identification of factors involved in muscle adaptation. The ability of muscle to adapt to meet functional demands is essential for mobility in normal daily life, in ageing well, in individuals with muscle diseases and nerve damage and in athletes. The ability of muscle to change its cellular composition is desirable for the livestock industry. Knowledge of how genes in muscle cells are regulated to adapt to demands has significant implications for public health and economic benefits. We have devised model systems that will allow us to identify the regulators of these genes in order to develop therapies to combat these changes in ageing and damaged muscle, to improve the quality of meat and optimise sport performance.Read moreRead less
A new paradigm of gene regulation - implications in embryogenesis and disease. The proposed analysis of a new paradigm of gene regulation will provide a new key to understanding genome function and inform some of the most compelling biological issues of our time such as stem cell biology, tissue and organ regeneration and genetic programming. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwi ....A new paradigm of gene regulation - implications in embryogenesis and disease. The proposed analysis of a new paradigm of gene regulation will provide a new key to understanding genome function and inform some of the most compelling biological issues of our time such as stem cell biology, tissue and organ regeneration and genetic programming. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwide, and assert Australia's leadership in this area of research.Read moreRead less