Molecular Analyses Of Flavivirus RNA Replication, Encapsidation, And Complementation
Funder
National Health and Medical Research Council
Funding Amount
$602,545.00
Summary
Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue. Hepatitis C virus is a member of the same virus family. Using Australian flavivirus Kunjin as a model and advanced techniques in molecular biology, biochemistry and electron micriscopy, the Flavivirus Research Unit at SASVRC has established itself as an international leader in the area of flavivirus RNA replication and ultrastructure of virus-infected cells. The objectives of this application are ....Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue. Hepatitis C virus is a member of the same virus family. Using Australian flavivirus Kunjin as a model and advanced techniques in molecular biology, biochemistry and electron micriscopy, the Flavivirus Research Unit at SASVRC has established itself as an international leader in the area of flavivirus RNA replication and ultrastructure of virus-infected cells. The objectives of this application are to advance further our understanding of how the flavivirus RNA replication complex is assembled, how it synthesizes RNA and how this RNA is specifically packaged to produce infectious virus. To achieve these goals we will employ state-of-the-art molecular biology techniques based on manipulations with infectious complementary DNA copy of Kunjin virus RNA. The intimate understanding of these mechanisms in flavivirus replication should facilitate the design of efficient antiviral drugs by specifically targeting unique events in RNA replication and-or packaging. This may assist in the development of antiviral drugs for treatment of infections caused by other higly pathogenic flaviviruses in Australia, such as dengue, Japanese encephalitis and Murray Valley encephalitis, as well as of the related heptitis C virus.Read moreRead less
Molecular Characterization Of Unique Recognition Sites On The Surface Of Human Spermatozoa
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
Developing an understanding of the molecular mechanisms that regulate human sperm function is central to the clinical management of male infertility, attempts to develop novel forms of male contraception and strategies for the introduction of transgenes into the male germ line. Defective sperm function is the largest single defined cause of human infertility. Despite the prevalence of this condition we have no idea how most cases of male infertility arise nor, in a vast majority of patients, do ....Developing an understanding of the molecular mechanisms that regulate human sperm function is central to the clinical management of male infertility, attempts to develop novel forms of male contraception and strategies for the introduction of transgenes into the male germ line. Defective sperm function is the largest single defined cause of human infertility. Despite the prevalence of this condition we have no idea how most cases of male infertility arise nor, in a vast majority of patients, do we understand which particular aspect of sperm biochemistry is defective. As a consequence we have not been able to develop sensitive biochemical diagnostic tests for the infertile male nor do we have any rational methods of treatment that address the cause of this condition. Similarly no new methods of male fertility regulation have been introduced since vasectomy despite the major advances that have been made in the field of female contraception over the same period of time. Clearly if we are to develop sensitive methods for the diagnosis of defective sperm function, introduce protocols for the treatment and prevention of male infertility and discover novel approaches to male contraception, we must first understand the cellular mechanisms that enable these highly specialized cells to perform their unique function. In this study we shall focus on one of the most important attributes of sperm function the capacity of these cells to recognize the egg. Once the biochemical basis of this fundamental recognition process is understood, it should pave the way for the development of clinical applications that target this signaling system with implications for a range of disciplines including reproductive toxicology, occupational medicine, family planning, infertility and biotechnology.Read moreRead less
Cancer is the result of multiple genetic errors, involving both the overactivity of growth-stimulating oncogenes and the loss of tumour suppressor genes. The identification of the genes in both of these categories is important if we are to understand and intervene in the disease. Tumour suppressors are the more difficult to identify, precisely because they are lost in cancer cells. Normally the task is extremely time consuming, tedious and expensive. We have developed a system which will provide ....Cancer is the result of multiple genetic errors, involving both the overactivity of growth-stimulating oncogenes and the loss of tumour suppressor genes. The identification of the genes in both of these categories is important if we are to understand and intervene in the disease. Tumour suppressors are the more difficult to identify, precisely because they are lost in cancer cells. Normally the task is extremely time consuming, tedious and expensive. We have developed a system which will provide a short-cut to the cloning of one such gene. We have started with the mouse version, which is lost in leukemic cells. We have mapped the gene to within a very small chromosomal region, and we have identified a biological effect which correlates with loss of the gene. Our next step is to combine these two approaches to clone the gene. Because these genes are always highly conserved between species, we will be able to quickly clone the corresponding human gene, the loss of which is very likely to be important in cancer of various types.Read moreRead less
RNA Binding Protein Musashi: Role In Folliculogenesis And Oocyte Development
Funder
National Health and Medical Research Council
Funding Amount
$419,223.00
Summary
Women in Australian have opted for social and economic reasons to delay both marriage and childbirth. Both infertility and congenital abnormality is associated with advancing maternal age as the ovarian pool of oocytes declines in number and quality. In this project we aim to gain an understanding of the molecular mechanisms underpinning healthy oocyte development. Insights gained have the potential to alleviate miscarriage, infertility and congenital abnormalities in Australian families.
Xenobiotics - Oxidative Stress In The Mammalian Ovary
Funder
National Health and Medical Research Council
Funding Amount
$377,922.00
Summary
Synthetic chemicals called xenobiotics in the environment are capable of interfering with female fertility. Xenobiotics can trigger oocyte depletion of the ovary and infertility. Exhaustion of the oocyte population results in the menopause, loss of ovarian hormones and profoundly affects female health through increasing susceptibility to heart and bone disease. This research will characterise xenobiotic effects on the ovary and will lead to significant advances in reproductive healthcare.