Exploring DNA Methylation As A Mechanism For Long-term Memory For Fear Extinction
Funder
National Health and Medical Research Council
Funding Amount
$415,322.00
Summary
Traumatic experiences are well remembered. In some cases, fear-related memories become debilitating and require therapeutic intervention to diminish the impact of these kinds of memories on daily living. Such therapies engage a process of inhibitory learning called fear extinction. Since anxiety disorders are particularly sensitive to relapse even after extensive exposure therapy, a deeper understanding of the extinction process is crucial if we are to develop more effective treatment protocols ....Traumatic experiences are well remembered. In some cases, fear-related memories become debilitating and require therapeutic intervention to diminish the impact of these kinds of memories on daily living. Such therapies engage a process of inhibitory learning called fear extinction. Since anxiety disorders are particularly sensitive to relapse even after extensive exposure therapy, a deeper understanding of the extinction process is crucial if we are to develop more effective treatment protocols for a variety of anxiety disorders.Read moreRead less
This study will address the idea that cancer commonly involves a genetic pathway that is normally used by stem cells to proliferate in an undifferentiated state. We have evidence to indicate that this system is active in cancer cells and believe this could explain how cancer cells manage to divide rapidly in a primitive state. This project may bring a new perspective to the study of malignant transformation and has the potential to reveal multiple new targets for cancer therapy.
Cell-specific Regulation Of The MicroRNA/RNAi Pathway
Funder
National Health and Medical Research Council
Funding Amount
$659,390.00
Summary
MicroRNAs are a group of molecules that are critical for controlling the activity of genes. They function in a diverse range of biological systems, such the brain and immune system. Although we know that these molecules are important, how they are made in cells is still poorly understood. Because these molecules have potential therapeutic applications, it is essential that we gain a precise understanding of their biology before we will be able to apply these to medicine.
The exciting field of small RNA research was the subject of the 2006 Nobel Prize in Medicine, and holds great potential in the diagnosis and prognosis of disease such as cancer. Recent clinical studies suggest that drugs inhibiting small RNAs called microRNA present novel therapeutic opportunities. By defining the non-specific effects of such drugs and investigating new avenues for their delivery, this project will secure the safe application of these drugs into the clinic.
Identification And Evaluation Of Novel Epigenetic Targets For The Treatment Of ? Haemoglobin Disorders
Funder
National Health and Medical Research Council
Funding Amount
$740,809.00
Summary
Symptoms of ?-haemoglobin disorders appear after birth, when fetal haemoglobin (HbF) is replaced by aberrant adult haemoglobin (HbA). Interestingly, the persistent expression of HbF in patients reduces disease severity. This observation has created much interest in understanding the fetal to adult transition, since reversing it can benefit patients. Epigenetics plays a central role to this mechanism. Identifying components of this switch will form the basis of next generation therapies.
MicroRNAs are a group of molecules that are critical for controlling the activity of genes. They function in a diverse range of biological systems, from early embryonic development to adult organs, such as the brain and immune system. Although we know that these molecules are important, there remain major gaps in our understanding of how they are produced. Thus, the goal of our research is to understand how cells make these molecules.
Thalassaemia, is a common inherited disorder affecting haemoglobin synthesis. Synthesis of ?/?-globin chain is balanced during normal red blood cell production. Any disruption in the ratio of ?/?-globin chain results in anaemia. In this study, we will explore gene therapy strategies to restore balanced ?:? globin expression and ultimately improve the severely anaemic phenotype in ?-thalassaemia patients.
Mechanism Of Leukaemia Suppression By The Transcription Factor Ikaros
Funder
National Health and Medical Research Council
Funding Amount
$655,630.00
Summary
A subset of acute lymphoblastic leukaemias are characterised by mutations in the Ikaros gene. These leukaemias respond poorly to chemotherapy and require novel therapeutic approaches. We have discovered a new function of Ikaros in regulating leukaemia cell death. This project investigates how Ikaros regulates cell death and whether this is a general mechanism. Understanding Ikaros function is a step toward improved treatments for this aggressive type of leukaemia.
Harnessing RNA Interference In Gene Therapy Vectors For ?-thalassaemia
Funder
National Health and Medical Research Council
Funding Amount
$719,188.00
Summary
There is an urgent need to develop safe and effective treatments for ?-thalassaemia. We anticipate that ?-globin-specific RNAi sequences will synergise with ?-globin transgene expression to achieve balanced ?-/?-globin ratio in a clinical setting. Given that one of the major issues with current gene therapy vectors is achieving high levels of expression, we believe this will be a more effective gene therapy strategy than ?-globin transgene expression alone.
Identification Of Epigenetic Regulators Of Lung Development
Funder
National Health and Medical Research Council
Funding Amount
$625,036.00
Summary
Adaptation to air breathing at birth is dependent on the generation of normal lung structure. Failure of lung formation and surfactant function results in respiratory failure at birth. Although progress has been made in identifying genes and pathways critical for lung function, the factors that control their expression, so called epigenetic factors, are not known. In this proposal, we will seek to identify these factors controlling lung formation.