A Bioinformatic Analysis And Structural Study On The Inositol Polyphosphate 5-phosphatases
Funder
National Health and Medical Research Council
Funding Amount
$421,320.00
Summary
Communication (or signaling) inside the cell enables the cell to respond to factors in its external environment, such as hormones or growth factors. The inositol phosphates and the phosphoinositides are signaling molecules that play an essential role in intracellular communication. The 5-phosphatases are able to modify these molecules and terminate, and in certain cases stimulate, signals. Failure to properly control intracellular signaling pathways may result in abnormal cell growth and cancer. ....Communication (or signaling) inside the cell enables the cell to respond to factors in its external environment, such as hormones or growth factors. The inositol phosphates and the phosphoinositides are signaling molecules that play an essential role in intracellular communication. The 5-phosphatases are able to modify these molecules and terminate, and in certain cases stimulate, signals. Failure to properly control intracellular signaling pathways may result in abnormal cell growth and cancer. Human 5-phosphatases are a complex family of enzymes: In addition to the region responsible for phosphatase activity (the catalytic domain) many members contain other protein modules . These associated domains may perform critical roles, such as regulating intracellular location and docking with other proteins. This project aims to perform a computational investigation of human 5-phosphatases and their associated domains. In particular we will search for novel phosphatases, investigate the evolutionary relationships between members of each domain family, and make testable predictions regarding the function of uncharacterized domains. This study will take advantage of data produced by the recently completed human genome project. The second aim of the project is to determine, using X-ray crystallography, the three-dimensional shape (or atomic structure) of a representative member of the 5-phosphatase family. Solving the structure of a 5-phosphatase at the atomic level is critical for understanding the nature of substrate specificity and for rational drug design.Read moreRead less
Integrated Analysis And Functional Characterisation Of Gene Amplicons In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$453,068.00
Summary
In Australia in 2001 there were ~1300 new cases of ovarian cancer. Survival of ovarian cancer is very poor and current treatments inadequate. To develop more effective treatments we need to understand the molecular events that cause ovarian cancer. Some genes have multiple copies in ovarian cancer cells and these may be good targets for therapy. We aim to find these genes and determine which ones have a functional effect in the tumour.
TGFB1 Is A Pivitol Regulator Of Endometriotic Lesion Development
Funder
National Health and Medical Research Council
Funding Amount
$438,749.00
Summary
Endometriosis occurs when the tissue that lines the womb is found in the pelvic cavity. 10% of reproductive aged women have endometriosis and suffer from debilitating pelvic pain and subfertility. We have shown that transforming growth factor (TGFB1) is central to the growth of endometriosis and that its absence suppresses disease development. We hope to clarify the role of TGFB1 in endometriosis, in order to develop better therapeutic options for women incapacitated by this disease.
Statistical Methods For Identifying Structural Variation In Tumour Genomes Using Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$243,458.00
Summary
New DNA sequencing technology can sequence a tumour genome affordably in 2 weeks. This re-sequencing data can be used to find small mutations and large-scale chromosomal rearrangements that together are the drivers of cancer. These may one day be used to guide cancer therapy. This project will develop new algorithms for finding mutations and apply these to discover the genetic basis of drug resistance in a model lymphoma system.
Many recent gene mapping efforts have focused on population based approaches instead of previously used family based approaches. One of the limiting factors with population based approaches is the cost of the technology - each participant must be evaluated (or genotyped) for hundreds of thousands of genetic markers. The cost can be reduced by using an approach which pools individuals together for genotyping, with statistical models used to deal with the problems that this creates.
Next-generation Sequencing Of Candidate Ovarian Tumour Suppressor Genes
Funder
National Health and Medical Research Council
Funding Amount
$101,899.00
Summary
In Australia in 2001 there were approximately 1300 new cases of ovarian cancer. Survival of ovarian cancer is very poor and current treatments inadequate. To develop more effective treatments we need to understand the molecular events that cause ovarian cancer. Some genes are inactivated by loss of a copy or mutation. We aim to find these genes using new DNA sequencing techniques.
Investigation Of The Anticancer Action And Cytotoxic-synergism Of Matrix Metalloproteinase Inhibition.
Funder
National Health and Medical Research Council
Funding Amount
$272,036.00
Summary
In virtually all cases, death from solid tumors (including breast cancer) results from invasion and metastasis. The exciting recent pre-clinical observations that a new class of anticancer agents (which primarily target tumour invasion and metastasis) operate synergistically with a number of standard chemotherapy cytotoxics (such as those already used to treat breast cancer) suggests a new and significant additional therapeutic potential for both agents. The basis of this synergism is completely ....In virtually all cases, death from solid tumors (including breast cancer) results from invasion and metastasis. The exciting recent pre-clinical observations that a new class of anticancer agents (which primarily target tumour invasion and metastasis) operate synergistically with a number of standard chemotherapy cytotoxics (such as those already used to treat breast cancer) suggests a new and significant additional therapeutic potential for both agents. The basis of this synergism is completely unknown however, and it is our contention that this mechanism needs to be explored at the molecular level in order to identify which combinations will have most potential in the clinic. This proposal aims to characterize synergistic combinations in an animal model of breast cancer progression, and to determine the specific molecular mechanism of the process. Each phase of the proposed study is a worthwhile undertaking in itself, and while it makes primary use of a breast cancer growth and metastasis system, the information revealed should be relevant to many tumour types. This information can be used to formulate new therapeutic strategies for the treatment of solid tumours and their metastasis in patients.Read moreRead less
Pathogenomics: New Ways To Exploit Genome Sequence Data From Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$547,372.00
Summary
Bacterial pathogens are locked in an evolutionary battle of survival with their eukaryote hosts. The rapidly evolving genes of medically-important pathogens are generally those required for adaptation to the human host. This project aims to exploit the abundance of available bacterial genome sequences to predict rapid evolution in bacterial pathogens using computational methods. The protein products of such genes offer novel targets for therapeutic intervention.
Regulatory RNAs Underlying Genetic Associations With Ankylosing Spondylitis
Funder
National Health and Medical Research Council
Funding Amount
$431,201.00
Summary
Ankylosing spondylitis is a chronic inflammatory disease affecting the spine and causing back pain. The diagnosis of the disease is delayed by up to 10 years due to lack of accurate tests. We aim to identify molecular signatures of the disease that might be used to distinguish inflammatory processes typical of the disease and other causes of back pain. This would allow earlier and more accurate diagnosis of the disease and result earlier patient treatment and better health outcomes.
The Contribution Of Upstream Open Reading Frames To The Eukaryotic Proteome
Funder
National Health and Medical Research Council
Funding Amount
$197,911.00
Summary
This project will investigate the novel idea that genomes of complex organisms (including human) 'double-dip' with many genes containing information for more than one protein. It will also examine if these small supernumary proteins have cell regulatory functions. If proved, it would significantly alter current views on the information content of higher vertebrate genomes. An understanding of the roles of these novel protein sequences may result in the development of new drugs.