The Formation And Development Of The Ovarian Follicular Membrana Granulosa
Funder
National Health and Medical Research Council
Funding Amount
$351,575.00
Summary
In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicle ....In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicles prior to her birth, ten of thousands in her reproductive years, and none at the menopause. Since she only ovulates about 500 in her lifetime most follicles die in the process of growing to ovulatory size. This project will examine the structure of the follicle wall and the cells that make up that wall. How these cells replicate during follicle growth has never been discovered. This research has important implications for the many women who have polycystic ovarian disease, whose follicles fail to grow to full size. We will be examining these ovaries directly. The research also has importance in the next phase of IVF developments.Read moreRead less
Tyrosine Kinases And Phosphatases In Cell Cycle Checkpoint Responses
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
In order for an organism to grow and develop, the cells that make up the tissues and organs need to undergo a process of cellular division, wherein individual cells grow and then divide into two cells. During this process of cellular growth and division the entire genome needs to be duplicated (this occurs during S-phase) and then divided equally into the two daughter cells. In S-phase several so-called 'checkpoint' mechanisms exist which ensure that this occurs in an orderly and precise manner. ....In order for an organism to grow and develop, the cells that make up the tissues and organs need to undergo a process of cellular division, wherein individual cells grow and then divide into two cells. During this process of cellular growth and division the entire genome needs to be duplicated (this occurs during S-phase) and then divided equally into the two daughter cells. In S-phase several so-called 'checkpoint' mechanisms exist which ensure that this occurs in an orderly and precise manner. The so-called 'DNA replication checkpoint' delays S-phase progression in response to 'replication stresses' that may otherwise cause DNA damage. Protein tyrosine kinases (PTKs) are hyperactivated in many human solid tumours and blood malignancies contributing to varied aspects of tumour progression. Our preliminary studies indicate that the inactivation of PTKs by protein tyrosine phosphatases may be essential for the suppression of S-phase progression in response to replication stress. Our goal is to understand the molecular mechanisms by which PTKs and tyrosine phosphatases contribute to S-phase checkpoints. Our studies will provide important insights into DNA replication stress-induced checkpoint responses in mammals and identify unprecedented mechanisms by which hyperactivated PTKs may contribute to tumour development.Read moreRead less
Viral Interference With Apoptosis: Defining The Mechanisms And Effects On Viral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$551,328.00
Summary
Apoptosis, or programmed cell death, is an orderly process whereby unwanted or damaged cells are removed from an organism. Deregulation of apoptosis has been implicated in the development of diseases such as cancer and autoimmunity. Therefore, a precise understanding of the mechanisms controlling the initiation of apoptosis has important clinical implications. In addition to removing unwanted cells, apoptosis functions as a defence mechanism to inhibit viral replication. Hence, in order to repli ....Apoptosis, or programmed cell death, is an orderly process whereby unwanted or damaged cells are removed from an organism. Deregulation of apoptosis has been implicated in the development of diseases such as cancer and autoimmunity. Therefore, a precise understanding of the mechanisms controlling the initiation of apoptosis has important clinical implications. In addition to removing unwanted cells, apoptosis functions as a defence mechanism to inhibit viral replication. Hence, in order to replicate efficiently viruses have evolved means to inhibit or interfere with apoptosis. The central aim of this work is to understand how two genes encoded by murine cytomegalovirus (MCMV) inhibit apoptosis and contribute to viral replication. MCMV is used as a model for human CMV (HCMV) infection. The majority of the human population is infected with HCMV which poses no risk to healthy individuals. However, reactivation of HCMV in people who are immunosuppressed such as transplant recipients or AIDS patiens is a significant cause of mortality. The MCMV infection model has provided important insights as to how the immune system controls infection and the mechanisms utilized by viruses to circumvent these processes. The proposed studies will improve our understanding of the processes that regulate viral replication. Understanding how viruses subvert host defence mechanisms will allow us to better understand their role in causing human disease, and thus, will provide key information for the design of improved anti-viral strategies. Importantly, the type of analyses proposed here will also contribute critical insights into the normal processes that control cell survival.Read moreRead less
Viral disease is a major health hazard in the modern world. SV40 is a relatively simple virus which must enter mammalian cells in order to replicate. As it does so, it causes the infected cell to divide and hence triggers tumour formation in the host. This proposal is aimed at understanding how SV40 enters cells, and then passes to the nucleus where it replicates. Most viruses have hijacked existing pathways into cells. For example, some viruses have used the pathway by which cells take up nutri ....Viral disease is a major health hazard in the modern world. SV40 is a relatively simple virus which must enter mammalian cells in order to replicate. As it does so, it causes the infected cell to divide and hence triggers tumour formation in the host. This proposal is aimed at understanding how SV40 enters cells, and then passes to the nucleus where it replicates. Most viruses have hijacked existing pathways into cells. For example, some viruses have used the pathway by which cells take up nutrients from the external medium. However, we have shown that SV40 uses a completely novel pathway involving surface pits called caveolae. The subsequent steps in the pathway are unknown and have been difficult to study. We have discovered a number of agents which inhibit infection by SV40. In this proposal we will characterise the infectious entry pathway by investigating exactly where in the cell these agents work. We will then isolate the virus from within the cell and attempt to reconstitute part of the viral entry pathway in vitro. These studies will provide insights into the entry pathway of the virus which may lead to new therapeutic strategies to combat viral disease. In addition, study of this pathway, leading from the cell surface to the nucleus, may provide new avenues for drug delivery and-or gene targetting.Read moreRead less
Mechanisms Underlying APOBEC3G Restriction Of HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
In the fight against worldwide HIV-AIDS, understanding natural cell defenses to the HIV virus may identify new virus targets and strategies to block HIV in humans. Here, we will use state-of-the-art, high resolution, fluorescent microscopy to understand how the recently identified cell protein, APOBEC3G, blocks the HIV life cycle in human cells. We anticipate that APOBEC3G will stop HIV from invading the nucleus of human cells to defend against HIV, a strategy we can apply to new therapies.
Regulation Of The Quality Of DNA Repair By Timing In The Cell Cycle
Funder
National Health and Medical Research Council
Funding Amount
$468,794.00
Summary
During responses to infection or immunisation, antibody-producing _B� cells mutate their antibody genes at extreme rates. Rare mutations which improve the antibodies are selected by competition between B cells favouring those which make the best antibodies: Darwinian evolution on extreme _fast-forward�. We aim to understand this process because it is essential for normal immunity and effective vaccination, and because when it goes wrong, it can cause aggressive human cancers.