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Trafficking Mechanisms Governing Receptor Availability For Signalling
Funder
National Health and Medical Research Council
Funding Amount
$526,978.00
Summary
Receptors on the cell surface allow cells to respond to their environment. We have recently discovered a new pathway for controlling the amount of receptors displayed on the cell surface, errors within which will lead to defects in development and diseases like cancer. We are studying how this new pathway controls the balance between how much receptors are destroyed after being activated and how much are recycled back for re-use.
Structural Studies Of The Jak And Abl Kinases: A Prerequisite For Drug Design
Funder
National Health and Medical Research Council
Funding Amount
$360,965.00
Summary
Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune related disorders. This fellowship aims to develop more potent kinase inhibitors of a number of PTKs using Cytopia’s drug discovery capability coupled with the X-ray crystallography expertise within Monash University. This innovative approach will permit a rational structure-based drug discovery platform to be established and will lead to the creation of a portfolio ....Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune related disorders. This fellowship aims to develop more potent kinase inhibitors of a number of PTKs using Cytopia’s drug discovery capability coupled with the X-ray crystallography expertise within Monash University. This innovative approach will permit a rational structure-based drug discovery platform to be established and will lead to the creation of a portfolio of phase I therapeutics, which will be of substantial benefit in the medical health area.Read moreRead less
Structural Investigation Into The Regulation Of The Colony Stimulating Factor Receptor, C-FMS.
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
The colony stimulating factor receptor, c-FMS is a member of a family of protein signalling molecules expressed on the cell surface that are implicated in the development of serious diseases in humans, such as inflammatory diseases and cancer. A number of important proteins bind to and regulate c-FMS in different ways. I intend to visualise these interactions to further understand how c-FMS activity is controlled by alternative means.
Neurons are highly compartmentalized cell-types. In neurodegenerative diseases such as Alzheimer's disease, the protein Tau that serves a distinct function in one cellular compartment (the axon) accumulates in a massively phosphorylated form elsewhere (somatodendritic compartments and their spines) which is believed to impair neuronal functions. We will investigate how Tau is distributed in health and disease, and determine how this distribution is regulated.
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
The Biology & Therapeutic Manipulation Of Lymphatic Vessels In Cancer & Lymphedema
Funder
National Health and Medical Research Council
Funding Amount
$2,589,101.00
Summary
This proposal brings together a team of researchers from diverse backgrounds who have already made important discoveries about the molecular control of the lymphatic system in normal physiology and cancer. The lymphatic vasculature consists of a network of vessels in organs and tissues that is critical for the regulation of tissue fluid volume and immune function. The lymphatics are also important for the metastatic spread of cancer, as they provide a route by which tumour cells spread to distan ....This proposal brings together a team of researchers from diverse backgrounds who have already made important discoveries about the molecular control of the lymphatic system in normal physiology and cancer. The lymphatic vasculature consists of a network of vessels in organs and tissues that is critical for the regulation of tissue fluid volume and immune function. The lymphatics are also important for the metastatic spread of cancer, as they provide a route by which tumour cells spread to distant sites in the body, and for lymphedema, a condition in which lymphatic dysfunction leads to swelling of tissues. This program will explore the molecular mechanisms that control the growth and differentiation of the lymphatic vessels. It will greatly enhance our understanding of lymphatic vessel growth (lymphangiogenesis) and generate a range of reagents for stimulating or inhibiting this process. These reagents will be tested in animal models for their capacity to modulate lymphatic function in the context of cancer and lymphedema.Read moreRead less