The Role Of The MYST Family Transcriptional Co-activator, Mof, In Embryonic Development
Funder
National Health and Medical Research Council
Funding Amount
$319,446.00
Summary
A major task in biology is to understand how the human genome directs the development of a single cell to form an entire individual. Clearly, a large part of this task is to understand how the expression of genes is regulated during embryonic development. Gene expression requires co-activator complexes. Co-activator complexes typically contain proteins which regulate the structure of chromatin (a complex of DNA and histones). However, the physiological function of most co-activators is entirely ....A major task in biology is to understand how the human genome directs the development of a single cell to form an entire individual. Clearly, a large part of this task is to understand how the expression of genes is regulated during embryonic development. Gene expression requires co-activator complexes. Co-activator complexes typically contain proteins which regulate the structure of chromatin (a complex of DNA and histones). However, the physiological function of most co-activators is entirely unclear. The aim of this project is to study the function of Mof during embryonic development. Mof is a co-activator that directly regulates chromatin structure by modifying histones. Mof is a member of the MYST family of co activators, which includes Moz and Qkf. We have recently shown that Moz and Qkf are essential for the haematopoietic stem cell population and the neural stem cell population, respectively. The purpose of this project is to produce a detailed analysis of the function of Mof in vivo and determine it's importance in regulating gene expression. All biological processes relay on accurate regulation of gene transcription and all diseases, whether they involve pathogens or cell intrinsic pathological changes, such as cancer, lead to changes in gene expression. Regulation of chromatin structure has been identified as a major mechanism of transcriptional regulation in health and disease. However, our understanding of the precise molecular mechanisms regulating chromatin structure in vivo are very limited. This work will fully investigate the role of an important co-activator in vivo including a mechanistic analysis. This will increase understanding of how gene expression is regulated and, ultimately, this knowledge will find wide application in the development of new treatment paradigms.Read moreRead less
Identification Of Genes Involved In Neural Crest Development
Funder
National Health and Medical Research Council
Funding Amount
$482,310.00
Summary
Knowledge of the genes that during embryonic development control the way our bodies form is necessary to understanding how our body systems function in health and disease. However, research on the developmental genetics of vertebrates, including humans, has proceeded very indirectly, mostly by looking for genes similar to those found in other biological systems, most notably the fruit fly. The significance of this research is that it will identify developmental genes directly from the chosen ver ....Knowledge of the genes that during embryonic development control the way our bodies form is necessary to understanding how our body systems function in health and disease. However, research on the developmental genetics of vertebrates, including humans, has proceeded very indirectly, mostly by looking for genes similar to those found in other biological systems, most notably the fruit fly. The significance of this research is that it will identify developmental genes directly from the chosen vertebrate body system as it develops. As a body system we will choose one of the most basic building blocks of the very early nervous system. This building block is an embryonic organ called the Neural Crest that later goes on to form important parts of the nervous system, but in addition it also forms major parts of the head and face, glands in the neck, the large arteries leading out from the heart, and pigment cells (melanocytes) in the skin. It is particularly important to gain insight into development of this organ because the tissues that derive from the neural crest are the most at risk for birth defects and for childhood cancers. Knowledge of neural crest development also tells us about our own evolution, because the neural crest is the only major system found only in vertebrates including humans.Read moreRead less
Functional Screening Of Novel Genes In Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Our faces are central to our ability to communicate, feed, breath and interact with each other. Birth defects that impact on the normal development of the face are common and affect not only the child but have a dramatic impact on the child's family as well. The genetic causes of most facial birth defects are unknown. This project will develop a method for determining how development of the face is controlled and will help identify genes that are responsible for facial birth defects.
Biological And Mathematical Studies Of Development Of The Enteric Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$390,250.00
Summary
During very early development in the embryo, cells migrate from the future brain. These cells, called neural crest cells, make there way to the nearest part of the gut, in the future oesophagus. They then migrate as a growing population right along the gut until they have populated the entire gut down to the rectum. To complicate matters, the gut itself is rapidly growing length-wise as this migration occurs. These neural crest cells then form the nerve cells that reside in the gut and which con ....During very early development in the embryo, cells migrate from the future brain. These cells, called neural crest cells, make there way to the nearest part of the gut, in the future oesophagus. They then migrate as a growing population right along the gut until they have populated the entire gut down to the rectum. To complicate matters, the gut itself is rapidly growing length-wise as this migration occurs. These neural crest cells then form the nerve cells that reside in the gut and which control gut function. In a common birth defect, Hirschsprung's disease, this migration stops short of the rectum so that the last part of the gut never develops nerve cells. This region lacking nerve cells is unable to propel the gut contents and, if untreated, this condition of intractable constipation is fatal after birth. Eight genes, when mutated, give essentially the same condition either in humans or animals, but the link between the genes and the condition is still not clear. We have proposed that the genes code for molecules that effect the way the neural crest cells interact with other neural crest cells and with the cells of the gut in which migration takes place. The link between the genes and the development of a normal gut nerve system (or its failure, as in Hirschsprung's disease) operates at the level of the dynamics of the neural crest cell population, interacting with the dynamics of gut growth. This project will use very detailed biological data acquisition to feed into newly formulated original mathematical models to tease out the important links between the neural crest cell population and the growing gut, that control cell migration. This will lead to an understanding of formation of the gut nerve system and of Hirschsprung's disease, at the population level, a level not well served by molecular levels of understanding. These models will have application in the many developmental contexts where cell movement and growth are simultaneous.Read moreRead less
The Role Of The HuB RNA-binding Protein In Post-transcriptional Gene Regulation In The Pre-gastrula Zebrafish Embryo
Funder
National Health and Medical Research Council
Funding Amount
$545,216.00
Summary
The precise control of protein expression is absolutely critical in biology. The key decisions about which genes are turned on or off at any one moment control the proper growth of an organism during development, and are responsible for the organism's homeostasis and proper response to environmental changes as an adult. The spatio-temporal control of genes is critcal during embryogenesis and we aim to understand how these processes underlie development in the vertebrate embryo.