Targeting The De Novo Serine Synthesis Pathway In Macular Disease
Funder
National Health and Medical Research Council
Funding Amount
$628,084.00
Summary
We have found a significant difference in de novo serine metabolism between the human primary Müller cells isolated from macular and peripheral retinas. We will study whether and how this difference contributes to redox homeostasis in these areas. The outcomes will help us to gain a better understanding of why the macula is more prone to develop disease than the peripheral retina.
Glial-neuronal-vascular Interactions In A Novel Transgenic Model Of Muller Cell Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$626,585.00
Summary
Muller cell disfunction is a feature shared by many retinal diseases. This project aims to study the contribution of Muller cell dysfunction to retinal neuronal damage and blood-retinal barrier breakdown in a novel transgenic model we recently generated. Results of this study will also be of interest to scientists and clinicians seeking to understand better and treat diseases of the central nervous system in general.
Muller Cell Reactivity During Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$258,000.00
Summary
Diabetes is the leading cause of blindness in the working population. In some patients with diabetes, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an increase in growth factors from cells within the retina called Muller cells. Muller cells are vital for the normal function of ....Diabetes is the leading cause of blindness in the working population. In some patients with diabetes, blood vessels within the retina proliferate, haemorrhage or cause retinal detachment. The underlying changes within the retina that lead to the proliferation of blood vessels are not well understood. One of the factors that leads to changes in retinal blood vessels is an increase in growth factors from cells within the retina called Muller cells. Muller cells are vital for the normal function of the retina and are known to be abnormal late in diabetes. They may also be dysfunctional early in diabetes and could play a significant role in causing the early changes seen in diabetes. Therefore a good understanding of how Muller cells change and the time at which they change is vitally important to gain a better understanding of the defects that are associated with diabetes. Furthermore, an understanding of the basic underlying cellular changes that occur in dibaetes will aid the development of more specific therapeutic agents in the future.Read moreRead less
A Mechanotransduction Apparatus To Coordinate Epithelial Collective Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$994,596.00
Summary
Epithelial cells migrate as physically coherent collective groups, which is necessary for normal development and is disrupted as cancers progress to become invasive and spread. Collective migration requires communication so that the behaviour of individual cells is properly coordinated. In this project we investigate how the transmission of physical force between cells allows them to communicate; and test how its disruption contributes to cancer invasion.
Investigating The Consequences Of Dysregulated Lipogenesis In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$600,647.00
Summary
Reprogramming of cellular metabolism is a hallmark of cancer. As such, there has been growing interest in developing strategies to exploit metabolism for therapeutic gain. Our ability to do this is dependent on a thorough understanding of the mechanisms by which dysregulation of cellular metabolism contributes to tumour progression. In this project, we seek to the investigate the fundamental mechanisms by which aberrant activation of lipid metabolism contributes to the tumourigenic process.
Function Of The Lysophospholipid Receptor Family In Neuronal Stem Cells And Their Progenitors.
Funder
National Health and Medical Research Council
Funding Amount
$380,723.00
Summary
Stem cells have the potential to give rise to a vast array of differentiated cells. Neuronal stem cells (NSC) can differentiate into progenitor cells which can themselves differentiate into cells of the nervous system: neurons and macroglial cells (astrocytes, oligodendrocytes, Schwann cells). This in turn can assist in the treatment of degenerative diseases such as multiple sclerosis, Parkinson's disease, motoneuron desease etc. Our project aims to study the effects on NSC and their progenitor ....Stem cells have the potential to give rise to a vast array of differentiated cells. Neuronal stem cells (NSC) can differentiate into progenitor cells which can themselves differentiate into cells of the nervous system: neurons and macroglial cells (astrocytes, oligodendrocytes, Schwann cells). This in turn can assist in the treatment of degenerative diseases such as multiple sclerosis, Parkinson's disease, motoneuron desease etc. Our project aims to study the effects on NSC and their progenitor cells of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), bioactive molecules known to play an essential role in the nervous system during development and inflammation. Our project aims to understand the mechanisms of action of these molecules in NSC maintenance, proliferation, differentiation and migration. By understanding how these molecules are able to regulate NSC biology will provide new avenues in the development of tools necessary for stem cell therapy.Read moreRead less
Regulation Of The Drosophila C-Myc Homologue In Stem Cell Growth And Division.
Funder
National Health and Medical Research Council
Funding Amount
$613,397.00
Summary
The mechanisms controlling stem cell growth and division require elucidation if we are to use stem cells in regenerative medicine and find cancer treatments. Due to experimental limitations such mechanisms are largely unknown in humans. We aim to use the vinegar fly as a model system to understand the importance of microenvironment to cancer gene control in stem cells. We will identify the secreted signals, from the neighbouring cells, required to control cancer initiation in stem cells.
Cell death by a specialised process known apoptosis is a way of deleting unwanted and harmful cells from the body. As such, aberrant apoptosis is associated with a wide array of diseases including cancer. For example, abnormal levels of proteins that suppress apoptosis or enhance cell survival can result in cancer and often produce resistance to chemotherapy. To understand and treat cancers that result from aberrant apoptosis we need to know at a molecular level how apoptosis is regulated. Centr ....Cell death by a specialised process known apoptosis is a way of deleting unwanted and harmful cells from the body. As such, aberrant apoptosis is associated with a wide array of diseases including cancer. For example, abnormal levels of proteins that suppress apoptosis or enhance cell survival can result in cancer and often produce resistance to chemotherapy. To understand and treat cancers that result from aberrant apoptosis we need to know at a molecular level how apoptosis is regulated. Central to the apoptosis execution are a group of enzymes called caspases that target many cellular proteins for specific cleavage. In this proposal, we will investigate the function of one of the caspases (called caspase-2), in order to better understand its potential role in the apoptosis of cancer cells. A number of recent reports suggest that caspase-2 levels are reduced in many cancer cells. The human caspase-2 gene localizes to a chromosomal region frequently affected- deleted in leukaemia, and caspase-2 levels have been proposed to be predictors of remission and survival in patients with some types of leukaemia. We will study if loss of caspase-2 in cancer cells makes them resistant to killing by drugs and if mice lacking caspase-2 have an increased potential to develop cancer. Understanding caspase-2 function and its regulation is likely to provide new therapeutic opportunities and potential targets for cancer therapy.Read moreRead less
Cytoskeletal Regulation Of Adhesion Structure And Cell Movement
Funder
National Health and Medical Research Council
Funding Amount
$60,420.00
Summary
Metastatic (secondary) cancers are a frequent cause of patient mortality. Central to the development of metastasis is cell motility-movement. A key component of cell movement is the way that cells bind and release the extra-cellular matrix as they move. By understanding how the dynamics of cell interaction with the matrix are regulated, we will identify molecules that are critical to the development of metastatic cancer and thus novel targets for inhibition of metastasis.