A Comprehensive Analysis Of Myb Target Genes Involved In Myelopoiesis And Myeloid Transformation
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
The MYB gene is essential for both normal blood cell formation and the growth of leukaemia cells. It acts by switching other genes (target genes) on and off. This project aims to advance our understanding of how MYB functions, by carrying out a comprehensive search for MYB target genes. In particular it will focus on target genes that help explain MYB's ability to control cellular growth and maturation. Some of these target genes may provide leads for future anti-cancer drug development.
Exploring Roles For MicroRNAs In Cancer Using Bioinformatics And Gene Expression Tools.
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
microRNAs are newly discovered chemicals that were the subject of the 2006 Nobel Prize in Medicine. These chemicals decrease the amount of specific molecular ‘targets’ in cells, and play an important role in cancer. Currently we do not understand how these chemicals choose their targets, and we propose to use a computer-based approach to discover how they affect genes in cancer. This will improve our understanding of cancer and thereby lead to the discovery of novel anti-cancer therapies.
Functional Analysis Of The P160 Myb-binding Protein - A Regulator Of Multiple Transcription Factors?
Funder
National Health and Medical Research Council
Funding Amount
$376,697.00
Summary
The c-myb gene is a key molecular regulator of normal blood cell production, but alterations to this gene can also lead to leukaemia. The protein (Myb) encode by the c-myb gene acts as a transcription factor, ie, it controls the activity of other genes. There is good evidence that interactions with other proteins can regulate the activity of Myb. Our laboratory has identified what we believe is one such protein - p160 - that binds to a part of Myb that reduces its activity, and thus that is like ....The c-myb gene is a key molecular regulator of normal blood cell production, but alterations to this gene can also lead to leukaemia. The protein (Myb) encode by the c-myb gene acts as a transcription factor, ie, it controls the activity of other genes. There is good evidence that interactions with other proteins can regulate the activity of Myb. Our laboratory has identified what we believe is one such protein - p160 - that binds to a part of Myb that reduces its activity, and thus that is likely to be responsible for regulating Myb. However, it has recently become apparent that p160 interacts with a number of other transcription factors in addition Myb. The primary aim of this project is to elucidate precisely how p160 interacts with Myb and what the consequences of this interaction are. A range of experimental approaches, which range from in vitro to genetic studies, will be employed to do this. We will test a specific role of p160 suggested by our preliminary studies - that of a transporter of transcription factors between the nucleus and the cytoplasm of the cell. Because of the wide range of transcription factors that p160 interacts with, its effects on the function of the cell are likely to be profound. For this same reason, it is difficult to specifically predict the possible medical-health implications of this work However, what we know to date is consistent with a role for p160 as a tumour suppressor gene. Moreover, parts of this project aim to generate genetic information and tools which will help in determining whether p160 does play such a role and generally, in identifying any other associations of p160 with particular diseases.Read moreRead less
Regulation Of Adult Colonic Crypt Homeostasis And Activation Of Colon Cancer Metastasis Genes By C-Myb
Funder
National Health and Medical Research Council
Funding Amount
$666,116.00
Summary
Regulation of normal colon biology and activation of genes involved colon cancer The c-myb gene is essential for the normal biology of the blood system and the colon. This gene is involved in regulating the balance between the production of new cells and their timely removal once they have completed their assigned tasks. There is a large body of evidence that supports the role of c-myb in the regulation of the blood system. We believe that the rules that govern the production of the huge number ....Regulation of normal colon biology and activation of genes involved colon cancer The c-myb gene is essential for the normal biology of the blood system and the colon. This gene is involved in regulating the balance between the production of new cells and their timely removal once they have completed their assigned tasks. There is a large body of evidence that supports the role of c-myb in the regulation of the blood system. We believe that the rules that govern the production of the huge number of cells needed to have a healthy blood system are similar if not identical to the rules used by the colon. This is because the colon also produces a massive number of cells each with special tasks and a defined life span of a few days. It is this rapid expansion of cell numbers and the programmed short life span of cells that necessitates multiple controls and very tight regulation. Furthermore if this process is hijacked by genetic changes that undermine these controls then there are numerous opportunities to initiate and potentiate malignant change or cancer. This project examines the role of the same genes in two contexts. Firstly when the genes are expressed at normal, highly regulated levels associated with the normal biology of the colon. The second context is when these genes are permitted to be over-expressed and thus drive processes for longer or in inappropriate situations leading to malignant growth.Read moreRead less
Alternative Splicing Of GLI1 And Its Role In Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$392,640.00
Summary
Gene expression involves the transfer of information from DNA to proteins and is mediated by a third molecule called messenger RNA (mRNA). The process is tightly controlled since unregulated gene expression is harmful and can result in diseases such as developmental disorders and cancer. The genetic information in DNA is first copied to an RNA molecule in a process called transcription. This RNA molecule then undergoes a series of maturation steps before the information it carries can be transla ....Gene expression involves the transfer of information from DNA to proteins and is mediated by a third molecule called messenger RNA (mRNA). The process is tightly controlled since unregulated gene expression is harmful and can result in diseases such as developmental disorders and cancer. The genetic information in DNA is first copied to an RNA molecule in a process called transcription. This RNA molecule then undergoes a series of maturation steps before the information it carries can be translated into a protein. One of these maturation steps involves the removal of sequences (called introns) that do not contain protein coding information from the sequences (called exons) that will be present in the mature mRNA. Some genes contain no introns while others contain 20 or more, which are dispersed throughout the gene. The removal of intron sequences from immature RNA molecules is called splicing and is carried out by a macromolecular complex that recognises the intron sequences, cuts them out of the RNA and then rejoins the RNA to make a contiguous sequence. This process has to be precise otherwise spurious sequences will be present in the mRNA, which will result in the production of abnormal proteins. In addition, for some genes mRNAs are produced that have differences in a portion of their sequence. These alternative sequences are generated by the inclusion or exclusion of alternative exons. Because, RNA splicing is critical to the production of mature mRNAs and because it can generate sequence diversity it is tightly regulated. We have recently found that expression of a cancer gene (called GLI1) is regulated in part by the use of alternative GLI1 mRNAs. Moreover, we found that the expression of one of these alternative GLI1 mRNAs is associated with skin cancer. In this project we will investigate the molecular mechanisms that regulate alternative splicing in GLI1 and identify whether changes in these mechanisms result in cancer.Read moreRead less