Coupling The Cell Cortex To Membranes: Structural Basis For The Activation And Control Of Ezrin
Funder
National Health and Medical Research Council
Funding Amount
$587,548.00
Summary
Cells are dynamic: they change shape, communicate with each other and import/export signalling molecules. These dynamic processes are controlled via the interaction of the cell membrane with the underlying actin cytoskeleton and they are important for health, for example, they are critical for proper immune cell function. The goal of this project in to unravel the control of membrane dynamics by defining the interactions between the cell membrane and the proteins: ezrin and RhoA.
In Vitro And In Vivo Investigation Of Actin Regulation In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$92,294.00
Summary
Malaria parasites move in a unique way. They move across cell surfaces and infect human cells using a unique molecular motor that allows them to, literally, glide. The research proposal outlined here is focused on understanding a key part of the motor – the dynamic protein actin – and by understanding how it is regulated develop new potential targets for novel drugs that might stop movement and, therefore, help prevent or treat malaria disease.
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