Cortactin: Molecular Regulation Of Cadherin Activity And Epithelial Morphogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Interactions between cells and their neighbouring cells control many important processes in the body. The adhesion molecule E-cadherin is a major protein that controls how cells interact with one another in many epithelial tissues (e.g. breast, lung, gut). These tissues are the source of many common diseases, particular cancer and inflammation. E-cadherin is essential for these tissues to form normally, and loss of E-cadherin function contributes to disease in these tissues (especially common ca ....Interactions between cells and their neighbouring cells control many important processes in the body. The adhesion molecule E-cadherin is a major protein that controls how cells interact with one another in many epithelial tissues (e.g. breast, lung, gut). These tissues are the source of many common diseases, particular cancer and inflammation. E-cadherin is essential for these tissues to form normally, and loss of E-cadherin function contributes to disease in these tissues (especially common cancers, such as breast and lung). Understanding how E-cadherin controls normal cell function in these tissues will therefore provide key insights into how disease arises. In this study we will investigate how a protein which binds to E-cadherin, cortactin, contributes to the biological effect of E-cadherin in supporting tissue architecture. Understanding the fundamental elements of how cortactin works with E-cadherin will provide invaluable information into how cells recognize one another in health, and fail to adequately recognize each other in common diseases.Read moreRead less
Microenvironmental Regulation Of The Tissue Regenerative Capacity Of Keratinocyte Stem Cells And Their Progeny.
Funder
National Health and Medical Research Council
Funding Amount
$391,762.00
Summary
The protective outer layers of the skin known as the epidermis belongs to a group of tissues in the body that are turning over at a rapid rate. The majority ofepidermal cells have a lifespan of just 2-3 weeks, and are shed as mature cells from the skin's surface. These cells are replaced by continuous cell regeneration which is dependent on growth factors and adhesive molecules (and other signals). It has recently come to light that the connective tissue of the skin i.e. the dermis, which lies d ....The protective outer layers of the skin known as the epidermis belongs to a group of tissues in the body that are turning over at a rapid rate. The majority ofepidermal cells have a lifespan of just 2-3 weeks, and are shed as mature cells from the skin's surface. These cells are replaced by continuous cell regeneration which is dependent on growth factors and adhesive molecules (and other signals). It has recently come to light that the connective tissue of the skin i.e. the dermis, which lies directly below the epidermal cells has a critical role in providing some of these factors required for their growth and maturation. Indeed, it is becoming increasingly clear that the epidermal and dermal cells co-operate to regulate epidermal proliferation and maturation. Recent work from our laboratory has shown that a newly recognised adhesive protein laminin-10 may be produced as the result of such co-operation and that it stimulates the growth of both normal and tumour epidermal cells. We have also recently identified an interesting subset of dermal cells that may have a role in promoting the growth of the epidermal cells. Thus, the aims of the proposed stuides are to investigate the role of laminin-10 and this specific dermal cell subset in epidermal proliferation and maturation. These studies may also provide an insight into the role of these factors in skin cancers.Read moreRead less
The Role Of The Intestinal Epithelium In Gliadin Peptide Influx In Coeliac Disease
Funder
National Health and Medical Research Council
Funding Amount
$503,566.00
Summary
Food products made from cereals such as wheat are part of the staple diet for much of the world but unfortunately they trigger coeliac disease in 1:100 individuals including more than 100,000 Australians. This project aims to determine where the disease inducing proteins cross the cells that line the intestine to enter the body. It also aims at increasing the health of these cells to produce a barrier that can prevent the disease inducing proteins from entering the body.
Characterisation Of Novel Cilia Proteins And Roles In Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$339,410.00
Summary
Cilia and flagella are tiny hair-like structures attached to the surface of most cells in the body. They perform different roles in many different organs including the brain and play key roles in our sensory systems. This project aims to identify and characterise components of cilia in order to better understand the causes of disorders where the cilia do not function properly.
Discovery And Analysis Of Vertebrate Intestinal Development Genes That May Play A Role In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$376,613.00
Summary
Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities ( ....Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities (mutations) that are acquired over the course of a lifetime. Together the mutated genes produce changes in cell behaviour in processes such as growth, migration, angiogenesis (the ability to attract a blood supply) and cell death. All of these processes are active during normal development of a vertebrate organism, but are generally shutdown in the adult state, except in cancer. In this study we will analyse a group of genes that we have recently shown to be indispensable for normal intestinal development in zebrafish. Zebrafish are small tropical fish that are used frequently for genetic studies. They are very closely related to mammals and it has been shown that the genetic pathways that control the development of this animal are highly conserved in fish and mammals. Importantly, the genetic pathways that lead to cancer in humans are also strikingly similar in zebrafish. Our experiments will use mouse models to discover whether the zebrafish genes we have identified can lead to cancer when they are aberrantly expressed in the intestines of mice. Any genes that are found to contribute to the development of cancer in these models could become potential new targets for cancer therapy.Read moreRead less
Progesterone Regulation Of Epithelial Expansion In The Normal Human Breast
Funder
National Health and Medical Research Council
Funding Amount
$556,393.00
Summary
The ovaries play a pivotal role in breast cancer. Progesterone increases breast cancer risk, and this is likely to be a subversion of its role in the normal breast, which is to participate in the normal expansion of the epithelial cells during the menstrual cycle, but how it does this is unknown. We will explore how progesterone influences cell types in the breast similar to those that become cancerous. This will uncover potential targets for prevention and treatment.
Glucose is a critical fuel for living organisms and its presence in the gut triggers nerves that slow stomach emptying. However, little is known of how glucose is actually detected in the gut. We have established that sweet taste molecules of the tongue are also present in the gut, where they may detect glucose. This research will measure the expression and function of these molecules in the gut of humans and mice, and reveal key information on their potential as targets in health and disease.
Regulation Of Epithelial Migration By Scribble In Development And Wound Repair
Funder
National Health and Medical Research Council
Funding Amount
$516,078.00
Summary
The movement of epithelial cells within our body (the cells that form the thin protective layer on exposed bodily surfaces such as skin and the lining of internal cavities, ducts, and organs) is essential for our normal embryonic development as well as for healing of wounds following injury. Understanding how this movement is regulated is therefore a fundamental area of medical biology. Although much is known about the mechanics of how a cell moves, the signals used to coordinate this movement s ....The movement of epithelial cells within our body (the cells that form the thin protective layer on exposed bodily surfaces such as skin and the lining of internal cavities, ducts, and organs) is essential for our normal embryonic development as well as for healing of wounds following injury. Understanding how this movement is regulated is therefore a fundamental area of medical biology. Although much is known about the mechanics of how a cell moves, the signals used to coordinate this movement so as to ensure that each cell migrates to the right place during embryonic development or in response to a wound is not well understood. A number of lines of evidence suggest that proteins required for the correct orientation of cells within our body (a property of cells known as polarity) may be essential for this process. Mutation of the polarity protein Scribble in the fly, zebrafish and mouse causes a disorganization of epithelial tissues during embryonic development. We have now shown that Scribble is required for cells to orientate correctly so as to be able to move in response to a wound in tissue culture and also during embryonic development and wound healing in the mouse. It is currently unknown how Scribble regulates migration. Here we propose to identify the molecules that Scribble regulates to coordinate cell movement during development and tissue repair. These studies will provide new insights into the fundamental process of how cell movement is coordinated and could lead to novel strategies for improved treatment of tissue injuries.Read moreRead less