Molecular Characterisation Of Telomere Trimming And Its Role In Cell Proliferative Capacity
Funder
National Health and Medical Research Council
Funding Amount
$403,439.00
Summary
Telomeres are protective structures at the ends of chromosomes. Telomere length is a major determinant of how many times a cell can proliferate. We have recently discovered a rapid telomere shortening process that we have called telomere trimming. We will analyse the molecular details of this process to determine whether it could be used to shorten telomeres and stop cancer cell proliferation, and whether blocking it could increase cell proliferation in patients with short telomere syndromes.
Epigenetic Determination Of Neuronal Vulnerability And Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$617,857.00
Summary
Neurons are faced with diverse forms of stress everyday. Neural diseases exacerbate this stress, causing interference to genes that normally allow neurons to function correctly. As a result, neurons die, and severe loss can result in diseases such as dementia. We have discovered new molecular factors in neurons that insulate their genes from stress, thereby protecting neuron function and health. The proposed research will exploit these mechanisms to better protect neurons from disease.
To Investigate The Role Of ATM Protein In Protecting Against Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$953,662.00
Summary
The overall aim of the project is to employ a rat model to investigate neurodegeneration in patients with ataxia-telangiectasia (A-T). Ataxia-telangiectasia is a complex multisystem disorder characterised by progressive neurological impairment, variable immunodeficiency and cancer predisposition. The rat model recapitulates the neurodegeneration in patients and thus this project will provide important insight into the nature of the defect as well as approaches for the treatment of the disorder.
Discovering The Function And Structure Of RIO Kinases – Toward New Nematocides
Funder
National Health and Medical Research Council
Funding Amount
$545,477.00
Summary
This project is focused on: high quality fundamental molecular science, contributing to national objectives, including the development of novel and innovative scientific concepts and international collaborations; consolidating links between basic and applied research; enhancing the skills-base in molecular biology and global visibility of Australian science.
Functional Dissection Of The Malaria RhopH Complex And Its Contribution To New Permeation Pathways
Funder
National Health and Medical Research Council
Funding Amount
$604,718.00
Summary
The ability of Plasmodium to invade and remodel its host erythrocyte are the most significant contributors to its ability to cause the disease malaria. This project aims to understand how proteins secreted from a specialized rhoptry organelle during erythrocyte invasion help Plasmodium to remodel the erythrocyte so that the parasite can gain access to the vital nutrients it requires for survival. This research will validate whether drugs targeting the rhoptry proteins are viable drug targets.
EEF1A1 Is Critical For HIV-1 Reverse Transcription And Replication
Funder
National Health and Medical Research Council
Funding Amount
$521,429.00
Summary
The project will investigate interaction between the AIDS virus, HIV-1, and the human cell it grows in specifically focusing on a human protein called eEF1A. Our research shows eEF1A is required for HIV-1 growth by regulating a step in the virus life cycle called reverse transcription. The goal of this project is investigate how interaction with eEF1A helps HIV-1 reverse transcription and to find drugs that block HIV-1 interaction with eEF1A.
Natural Treg are dependent on the transcription factor FOXP3, but the mechanism of action of FOXP3 is only now becoming defined for human Treg. Tregs are critical for a balanced, responsive immune system, and deviation from this balance results in autoimmune diseases or persistence of cancers. In order to intervene to treat these disease it is essential to first know what makes a normal Treg function, and to then compare this with the disease so that faulty genes can be targeted for intervention ....Natural Treg are dependent on the transcription factor FOXP3, but the mechanism of action of FOXP3 is only now becoming defined for human Treg. Tregs are critical for a balanced, responsive immune system, and deviation from this balance results in autoimmune diseases or persistence of cancers. In order to intervene to treat these disease it is essential to first know what makes a normal Treg function, and to then compare this with the disease so that faulty genes can be targeted for intervention with new drugs or a cell therapy.Read moreRead less
Interaction Of TRF2 With DNA Repair Proteins In Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$297,246.00
Summary
10-15% of human cancers, including some of the most difficult-to-treat and aggressive, depend for their continuing growth on a molecular process called Alternative Lengthening of Telomeres (ALT). We have identified for the first time a protein whose normal role includes repressing ALT. We will study how this protein works, what its molecular partners are, and how these molecules interact with each other. This information is expected to lay the foundations for cancer treatments that target ALT.
Epigenetic Therapies To Differentiate And Eradicate Leukaemia Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$674,315.00
Summary
Leukemia stem cells (LSC) are often resistant to conventional and targeted therapies and therefore serve as the seed for leukaemia relapse. The overall aim of this project is to use small molecule therapies to block the activity of a particular protein (LSD1) in LSC in order to differentiate them and expose a vulnerability to another epigenetic therapy called a BET inhibitor. Together, these epigenetic therapies will differentiate and eradicate LSC, leading to improved outcome in AML.
Chromosomal translocations in the MLL gene results in aggressive leukaemias. Several drugs developed to target proteins that interact with the MLL fusion proteins are now being tested in the clinic. Despite this progress, our understanding of how the MLL fusion proteins cause leukaemia remains incomplete. In particular, it is unclear how the MLL fusion protein drives the development of leukaemia. In this project I will address these important issues with cell and molecular biology methods.