Stem And Progenitor Cell Contribution To Skin Wounds And Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Skin wounds represent a major health and economic burden. Although skin stem cells have been used routinely for the treatment of wounds, they cannot reconstitute a fully functional skin given the complexity and the many cell types usually involved in wound healing. In this project, we intend to evaluate the role of different cell populations on modulating skin wound healing to produce more regeneration and less scaring.
Identification Of Novel Mediators Of Bone Catch-up Growth
Funder
National Health and Medical Research Council
Funding Amount
$1,043,810.00
Summary
Musculoskeletal growth disorders cause significant suffering in children and impair new workforce generations before their working life starts. Despite this relevance, non-invasive methods to induce growth recovery of impaired bones are an unmet need, as we lack sufficient understanding of how this process works. To address this knowledge gap, we generated mouse models that will allow us to reveal foetal mediators of compensatory growth that could be reactivated postnatally to boost bone growth.
The intestinal lining is continuously renewed by specialised cells called intestinal stem cells. Stem cells throughout the body are regulated by nearby connective tissues. But, the identity of these supportive cells in the gut are unknown. We test whether a discrete population of connective tissue cells in the gut support intestinal stem cells. This project will identify new cellular therapies and targets to promote intestinal repair and manage intestinal cancer.
Characterization Of The 72 KDa Inositol Polyphosphate 5-phosphatase
Funder
National Health and Medical Research Council
Funding Amount
$454,050.00
Summary
Cells respond to external signals and the enviroment to undergo cell growth, secretion and or other specialized functions including control of cell death and or cell size. We have identified a new enzyme (72 kDa 5-phosphatase) which resides inside the cell, which we have evidence plays a role in regulating both the movement of intracellular vesicles and also lipid signals stimulated by insulin. We have characterised the phospholipids that the enzyme cleaves and demonstrated the generation of new ....Cells respond to external signals and the enviroment to undergo cell growth, secretion and or other specialized functions including control of cell death and or cell size. We have identified a new enzyme (72 kDa 5-phosphatase) which resides inside the cell, which we have evidence plays a role in regulating both the movement of intracellular vesicles and also lipid signals stimulated by insulin. We have characterised the phospholipids that the enzyme cleaves and demonstrated the generation of new cell signals at specific subcellular localizations on intracellular membranes. We predict the generation of these specific lipid signals may play a significant role in controlling the transport of intracellular cargo to specific sites in the cell. In this grant proposal we aim to examine the regulation of specialised cargo called the glucose transporter, which is found in fat and muscle cells, and also the mannose 6-phosphate receptor, which regulates the trafficking of specific enzymes which mediate digestion of proteins. These studies include the clarification of which phospholipid signals the enzyme terminates and where in the cell this occurs. Secondly, we will examine the movement of the glucose transporter GLUT-4 in unstimulated cells and in response to insulin and furthermore how expression of the novel enzyme regulates its movement. We will also examine the movement of the mannose 6-phosphate receptor and the specific phospholipid signals which control the route the receptor traffics, using inhibitors of lipid signals and expression of lipid phosphatases and kinases. We will also examine how our novel enzyme forms complexes with other molecules in the cell and characterise these novel molecules using basic biochemical assessment of enzyme activity and function. Finally we will examine the regulation of intracellular messages by our novel enzyme following insulin stimulation, which facilitates glucose uptake into the cell.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
Aberrant Mesenchymal-epithelial Transition: A Pathogenic Mechanism In Tissue Maintenance And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$522,299.00
Summary
The causative genetic factors associated with aberrant changes of cellular properties are identified by analysing the profile and the control mechanism of gene expression. Specifically,this project will reveal how the transition of different patterns of tissue organization may be manifested in birth defects and malignant diseases.