Intra- And Intercellular Spreading In Shigella Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$216,318.00
Summary
Each year Shigella flexneri bacteria cause over 167 million episodes of dysentery and over 1 million deaths worldwide, under conditions of poor sanitation, in both developed and developing countries. No vaccines are available, and resistance to antibiotics is common. This project will study the a key part of the machinery that allows bacteria use to cause disease, and also to identify drugs that block the machinery which can in future be used to treat infection by these bacteria.
Dissecting The Molecular Basis Of Actin Filament Disassembly In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$576,716.00
Summary
Cell movement by the malaria parasites is fundamental to parasite infection and disease. However, whilst core components of the parasite motor driving movement are known, little is understood about their regulation, in particular actin – the dynamic force behind all parasite motility. Here by dissecting the role of actin-depolymerizing-factor-1, an essential parasite actin regulator, we hope to reveal one of the central processes that underlies motility and develop it into a potential drug targe ....Cell movement by the malaria parasites is fundamental to parasite infection and disease. However, whilst core components of the parasite motor driving movement are known, little is understood about their regulation, in particular actin – the dynamic force behind all parasite motility. Here by dissecting the role of actin-depolymerizing-factor-1, an essential parasite actin regulator, we hope to reveal one of the central processes that underlies motility and develop it into a potential drug target.Read moreRead less
Dissecting The Molecular Basis For Cell Movement And Midgut Colonisation In The Insect Stage Parasite - The Ookinete
Funder
National Health and Medical Research Council
Funding Amount
$48,365.00
Summary
Malaria parasites are a leading cause of infant mortality. Despite their global impact, no vaccine exists to prevent malaria disease and resistance to current drugs is prevalent. Cell movement is an essential process for parasite development yet its potential as a drug target remains unexplored. I seek to shed light on the molecular mechanisms underlying movement, focused on the motile insect stages. Understanding gained here will support the broader goal to identify targets for transmission-blo ....Malaria parasites are a leading cause of infant mortality. Despite their global impact, no vaccine exists to prevent malaria disease and resistance to current drugs is prevalent. Cell movement is an essential process for parasite development yet its potential as a drug target remains unexplored. I seek to shed light on the molecular mechanisms underlying movement, focused on the motile insect stages. Understanding gained here will support the broader goal to identify targets for transmission-blocking development.Read moreRead less
Inhibition Of Cellcell Actin-based Motility During Poxvirus Infection By The Kinase Inhibitor Glivec
Funder
National Health and Medical Research Council
Funding Amount
$92,950.00
Summary
Although smallpox, one of the deadliest human pathogens, was eradicated in 1980, the current global climate has resulted in fears that smallpox may be used as a biological weapon. Unfortunately the smallpox vaccine poses a serious health hazard to certain people. We have shown that Glivec, a drug used to treat cancer, has potent anti-viral affects on poxvirus replication. This project will test the effectiveness of Glivec in treating smallpox in an animal model and study how it acts.
New Role For The E3 Ligase E6AP In The Control Of Cell Motility And Invasion
Funder
National Health and Medical Research Council
Funding Amount
$462,162.00
Summary
Cell motility and invasion are fundamental process in normal cellular functions, however, when deregulated they can lead to metastatic cancer, a leading cause of cancer mortality and morbidity worldwide. Detailed understanding of the mechanisms governing these processes is essential for the development of new targets to prevent metastatic cancer. We discovered a protein that control these processes, which renders it an important target to investigate.
MECHANISMS OF MOTILITY AND METASTASIS In BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$209,505.00
Summary
The broad aim of this proposal is to elucidate novel molecular mechanisms of breast cancer cell motility that are relevant to metastasis or the spread of cancer. The function of two genes will be studied. We propose that (1) reduced on-random motile (ROM) regulates the speed of cancer cell movement, and (2) Neural Wiskott-Aldrich syndrome protein (N-WASP) regulates the directional component of cell movement. We will relate the function of ROM and N-WASP to rapid, linear walking along collagen fi ....The broad aim of this proposal is to elucidate novel molecular mechanisms of breast cancer cell motility that are relevant to metastasis or the spread of cancer. The function of two genes will be studied. We propose that (1) reduced on-random motile (ROM) regulates the speed of cancer cell movement, and (2) Neural Wiskott-Aldrich syndrome protein (N-WASP) regulates the directional component of cell movement. We will relate the function of ROM and N-WASP to rapid, linear walking along collagen fibres in live tumours and to breast cancer metastasis to the lung. ROM will be inhibited in breast cancer cells and we expect increases in both the speed of cell movement and metastasis. Therefore, ROM functions as a suppressor of metastasis. Inhibition of N-WASP, however, is expected to compromise both the directionality of cell movement and metastasis. N-WASP is therefore, a promoter of metastasis. At the completion of this work, the regulatory mechanisms of motility and metastasis by ROM and N-WASP will be defined. This will facilitate the development of biologically targeted agents for ROM and N-WASP that can be used to control metastasis. In addition, these agents that target the motility pathway are appropriate for use in combined therapy with agents that target a different pathway such as survival or growth. This will significantly improve disease control rates or the proportion of patients with partial or complete disease regression. This proposal addresses the National Health Priority, cancer, and related National Research Priority, ageing well and ageing productively, where in the longer term, we will be able to create new and much needed therapy for metastasis.Read moreRead less
Regulation Of Signal Transduction By Cbl: Investigation Of Effects On The Cytoskeleton, Cell Adhesion And Cell Motility
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
Changes in cell adhesion and motility have been implicated in a wide range of human pathologies (e.g. immune, reproductive, mental, and cancerous disorders) . Cell adhesion and motility are tightly regulated by a group of proteins known as Rho-GTPases. Novel pharmacological agents that target signalling by Rho-GTPases have been demonstrated to profoundly affect tumour metastasis, as well as central nervous system regeneration following injury. Further exploitation of Rho-GTPase signal modulation ....Changes in cell adhesion and motility have been implicated in a wide range of human pathologies (e.g. immune, reproductive, mental, and cancerous disorders) . Cell adhesion and motility are tightly regulated by a group of proteins known as Rho-GTPases. Novel pharmacological agents that target signalling by Rho-GTPases have been demonstrated to profoundly affect tumour metastasis, as well as central nervous system regeneration following injury. Further exploitation of Rho-GTPase signal modulation, by detailed studies of the molecular mechanisms involved, could lead to significant advances in medical sciences. In particular, treatment of cancer and spinal injuries are likely to benefit from further development of Rho-signalling research.Read moreRead less
TRANSCUTANEOUS ELECTRICAL STIMULATION TO TREAT CONSTIPATION DUE TO ANORECTAL RETENTION IN CHILDREN
Funder
National Health and Medical Research Council
Funding Amount
$635,320.00
Summary
If you don't poop, you die! Over 20% of older people have constipation. It starts in childhood in 1/100 people and lasts through life. At the Royal Children’s Hospital, Melbourne, we have been developing a physiotherapy method using electrical stimulation across the skin to treat long-term constipation. In this study we are comparing this treatment to current treatment in the most common type of chronic constipation in children.