Modulation Of Virus-cellular Receptor Interactions In Picornaviral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$422,036.00
Summary
Gastrointestinal viral infections of humans result in a wide variety of illnesses ranging from the common cold to infantile paralysis and viral myocarditis. Despite the wide range of tissues and organs targeted by these viruses, the manner in which infection is initiated is remarkably similar. The primary step in infection is the binding of a virus to a specific protein on the cell surface, similar to the lock and key analogy. This project seeks to investigate the nature of interactions between ....Gastrointestinal viral infections of humans result in a wide variety of illnesses ranging from the common cold to infantile paralysis and viral myocarditis. Despite the wide range of tissues and organs targeted by these viruses, the manner in which infection is initiated is remarkably similar. The primary step in infection is the binding of a virus to a specific protein on the cell surface, similar to the lock and key analogy. This project seeks to investigate the nature of interactions between representative picornaviruses and their cellular attachment proteins with a view to designing rational anti-viral strategies to block virus cell attachment and cell entry. Using the data raised when investigating why some viruses only infect certain cells, we plan to target human tumors cells based on their susceptibilty to different viruses.Read moreRead less
Recycling Of E-cadherin: Implications For Dynamic Cell Adhesion
Funder
National Health and Medical Research Council
Funding Amount
$250,494.00
Summary
E-cadherin is one of the major proteins responsible for mediating cell-to-cell adhesion in the body. During embryonic development E-cadherin is essential for establishing the normal body pattern and the cellular architecture of many epithelial organs. Throughout life E-cadherin serves to maintain epithelial barriers, such as the lining of the digestive tract. E-cadherin has been clearly identified as a tumour suppressor molecule: loss of normal E-cadherin function leads to tumour metastasis and ....E-cadherin is one of the major proteins responsible for mediating cell-to-cell adhesion in the body. During embryonic development E-cadherin is essential for establishing the normal body pattern and the cellular architecture of many epithelial organs. Throughout life E-cadherin serves to maintain epithelial barriers, such as the lining of the digestive tract. E-cadherin has been clearly identified as a tumour suppressor molecule: loss of normal E-cadherin function leads to tumour metastasis and cancer invasion. It is therefore essential to understand the physiological function and regulation of E-cadherin in cells. E-cadherin is normally expressed on the surface of cells for adhesion to neighbouring cells. Recently, we found that cells can internalise and recycle this surface E-cadherin: even in mature epithelia, a proportion of the E-cadherin molecules appear to undergo constant movement in and out of the cell. It is likely that this mechanism participates in the dynamic remodelling of adhesive contacts between cells in organs such as the gastrointestinal tract and during wound healing. Corruption of this recycling mechanism could also potentially contribute to tumorigenesis. In this grant we propose to build upon this discovery by investigating molecular and cellular mechanisms that mediate E-cadherin recycling. We will characterize the cellular pathways by which E-cadherin is trafficked. The signaling pathways that regulate recycling will be analysed, since these may be perturbed in cancer and inflammation. Other molecules that interact with E-cadherin will be studied to determine whether they too recycle. The information from these studies will have broad implications for understanding the role of E-cadherin in healthy organs and in common cancers.Read moreRead less
I am a molecular geneticist with a special interest in molecular pathology determining the inherited and somatic genetic events that predispose to, and advance cancer development. Much of this work has immediate translatability to clinical genetics practi
The Role Of TGF-beta Signaling In Suppression Of Stat3-mediated Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$667,000.00
Summary
Stomach cancer is the third most prevalent cancer in the Western World and result in the yearly death of several thousand people in Australia alone. We have discovered a specifice gene mutation of a receptor molecule called gp130 that results in the formation of stomach cancer in mice. We are now aiming to understand the exact molecular events by which this mutation results in the uncontrolled growth of stomach mining cells. Our proposal combines the expertise of the two investigators in signal ....Stomach cancer is the third most prevalent cancer in the Western World and result in the yearly death of several thousand people in Australia alone. We have discovered a specifice gene mutation of a receptor molecule called gp130 that results in the formation of stomach cancer in mice. We are now aiming to understand the exact molecular events by which this mutation results in the uncontrolled growth of stomach mining cells. Our proposal combines the expertise of the two investigators in signal transduction and the making of genetically modified mouse models. These strategies will be employed to specifically address in the laboratory mouse the function of two specififc signaling cascades, called Stat3 and TGF-beta. The identification of detailed description by which these molecules causally relate to cancer formation will provide clear and specific molecular targets for future therapies to treat various cancers, including those of the stomach.Read moreRead less
Differential Cooperation Of MAPKs With TGF-beta Signaling In Epithelial-Mesenchymal Transition
Funder
National Health and Medical Research Council
Funding Amount
$497,250.00
Summary
Tumor metastasis - the spread of tumor cells from the original site of growth to other sites in the body, is the biggest threat to survival for patients with solid tumors. The most damage change during cancer progression is the switch from a locally growing tumor to a metastastic killer. For biologist studying cancer, a major challenge is to identify the molecular and cellular mechanisms underlying the switch of non-invasive tumor to an invasive, metastatic state. This application aims to identi ....Tumor metastasis - the spread of tumor cells from the original site of growth to other sites in the body, is the biggest threat to survival for patients with solid tumors. The most damage change during cancer progression is the switch from a locally growing tumor to a metastastic killer. For biologist studying cancer, a major challenge is to identify the molecular and cellular mechanisms underlying the switch of non-invasive tumor to an invasive, metastatic state. This application aims to identify key molecular and cellular mechanism controlling this switch, with the ultimate aim being to devise treatments that inhibit tumor metastasis. The results from this work will provide clear and specific targets to prevent and to treat tumor metastasis. More importantly, the success of strategies used in this work can potentially be used clinically for tumor treatment.Read moreRead less
Aberrant Transcriptional Signalling In The Progression And Metastasis Of Melanoma.
Funder
National Health and Medical Research Council
Funding Amount
$353,033.00
Summary
There are currently no treatments that have any impact on decreasing mortality from metastatic melanoma. We have found 2 new variants in melanoma that may control the tumour growing and invading around the body. This study will examine the protein containing these changes with the aims of finding how they function differently, to identify their roles in the formation of melanoma, as well as to identify new targets for prevention and treatment of metastatic disease.
Deciphering Tumour Heterogeneity Of Breast Cancer Metastases Using Barcoded Patient Derived Xenografts
Funder
National Health and Medical Research Council
Funding Amount
$583,161.00
Summary
Breast cancer mortality is largely due to metastases that seed from the primary tumour. Breast tumours are known to contain a heterogeneous mix of cells, but the precise way that cells are selected for tumour growth and metastasis (as well as their response to systemic therapy) is not well understood. In this study we will use patient samples and cellular ‘barcoding’ to track the destiny of every single clone throughout disease progression and study the effect of various therapies on metastasis.