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Transcriptional Regulation Of The Complement Receptor 2 Gene (CR2/CD21) During B Cell Lineage Committment
Funder
National Health and Medical Research Council
Funding Amount
$466,500.00
Summary
The complement system is a very important pathway within the human immune system. One of the receptors within this system is complement receptor 2 or CR2. CR2 has not only been shown to be important within the inflammatory response and defence against microbes but is also important in normal generation of a B cell immune response . B cells not only produce antibodies against foreign organisms but in some cases dysfunction of the B cell can bring about autoimmunity by production of antibodies aga ....The complement system is a very important pathway within the human immune system. One of the receptors within this system is complement receptor 2 or CR2. CR2 has not only been shown to be important within the inflammatory response and defence against microbes but is also important in normal generation of a B cell immune response . B cells not only produce antibodies against foreign organisms but in some cases dysfunction of the B cell can bring about autoimmunity by production of antibodies against self tissues and cells . How the CR2 gene turns on expression on different cells within the immune system is complex. The amount of receptor on the surface of antibody producing B cells has important implications to B cell biology. As CR2 expression is turned on at an important point within the antibody producing B cell and the levels of this receptor can influence B cell function, understanding how this gene is regulated is important.Read moreRead less
A major feature of tumour progression and cardiac hypertrophy (enlarged heart) is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy and hypertrophy suggesting that it may play a causal role in tumour formation and cardiac disease. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective at inhibiting the growth of some tumours and vascular smooth ....A major feature of tumour progression and cardiac hypertrophy (enlarged heart) is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy and hypertrophy suggesting that it may play a causal role in tumour formation and cardiac disease. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective at inhibiting the growth of some tumours and vascular smooth muscle. This study will examine the mechanisms that regulate ribosome synthesis. Specifically it focuses on a transcription factor termed UBF whose activity we think is critical for the regulation of the synthesis of the ribosomal RNA, the catalytic backbone of the ribosomes. Understanding the molecular mechanism(s) controlling UBF function will lead to a better comprehension of how cells modulate synthesis of functional ribosomes and how this process is deregulated during disease states associated with deregulated protein synthesis and growth such as cardiac hypertrophy and cancer.Read moreRead less
The Regulation Of Gene Expression During Adipogenesis
Funder
National Health and Medical Research Council
Funding Amount
$549,446.00
Summary
The body stores energy acquired from ingested food as fat droplets within storage cells termed adipocytes. The amount of fat varies between individuals and may also vary during an individual's life. The variations reflect differences in physiology, diet, and behaviour and have been the focus of intense study. Excessive accumulation of fat is a serious health problem as it is associated with conditions such as heart disease and diabetes. This grant application primarily concerns using a new line ....The body stores energy acquired from ingested food as fat droplets within storage cells termed adipocytes. The amount of fat varies between individuals and may also vary during an individual's life. The variations reflect differences in physiology, diet, and behaviour and have been the focus of intense study. Excessive accumulation of fat is a serious health problem as it is associated with conditions such as heart disease and diabetes. This grant application primarily concerns using a new line of genetically modified mice that have reduced fat. These mice lack a key gene regulatory protein that is implicated in fat accummulation and adipocyte formation. It is expected that a knowledge of the genes regulating the formation and function of fat storage cells will contribute to new strategies for controlling fat formation and will help in the prevention of diseases such as diabetes and heart disease.Read moreRead less
This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less
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