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.
Generation Of Human Intestinal Stem Cells By Direct Reprogramming
Funder
National Health and Medical Research Council
Funding Amount
$630,391.00
Summary
Intestinal stem cells (ISCs) can give rise to mini guts in vitro with exciting applications for drug screening and cell based regenerative medicine. However, currently the establishment of mini gut cultures requires an invasive procedure. By taking advantage of a revolutionary new predictive algorithm (Mogrify) we will generate ISC directly from somatic and pluripotent cell sources.
Building An Intestine: Manipulating Regeneration Of The Epithelium
Funder
National Health and Medical Research Council
Funding Amount
$609,424.00
Summary
Diseases, infections and pathologies are common clinical problems of the intestinal lining in both infants and adults. Individuals with these conditions can experience nutritional problems and severe cases result in death. The intestinal lining is generated from a small population of stem cells. In this study we use of a mouse model where the stem cells are marked and will examine what factors regulate stem cells in the intestine with the aim of facilitating intestinal tissue regeneration.
Using Direct Reprogramming To Generate And Rejuvenate Haematopoietic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,026,313.00
Summary
One of the greatest promises of regenerative medicine lies in our ability to reprogram any cell type of the body into any other cell type. Transdifferentiation is the conversion of one adult cell type to another and it is believed to be the next frontier in regenerative medicine therapies since it can be used in vivo for the direct conversion of one cell type into another. The outcomes of this grant will push the limits of these technologies to generate new regenerative medicine strategies.
Generating Haematopoietic Stem Cells From Human Pluripotent Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$872,215.00
Summary
Blood stem cell transplantation is a vital therapy for patients with leukaemia following chemotherapy or for patients with bone marrow failure. Because many patients lack a donor, there is a need for an alternate source of stem cells. Using a new approach that we have developed, our laboratories will make blood stem cells from human pluripotent stem cells that will treat patients needing a transplant.
Characterization Of HOXA-expressing Human Haematopoietic Cells Generated From Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$622,464.00
Summary
Blood stem cell transplants are used for treating a range of human blood disorders such as leukaemias. However, for many patients, suitable donors cannot be found. We are searching for ways in which embryonic stem cells can be turned into blood stem cells in the laboratory to provide a new source of these cells that could then be used to treat patients.
Twist-1 Inhibits MSC Osteoblast Differentiation During Osteoporosis Via Direct Regulation Of The Wnt Signalling Pathway
Funder
National Health and Medical Research Council
Funding Amount
$482,704.00
Summary
There is a predicted dramatic increase in the number of orthopaedic related problems that require surgical intervention and rehabilitation therapy in the coming decade associated with higher incidences of bone diseases as a consequence of an aging population. This proposal seeks to determine whether the transcription factor, Twist-1 plays a central role in regulating the growth and differentiation of skeletal progenitors during bone loss following the onset of osteoporosis.
Transcriptional Regulation Of Definitive Hematopoietic Development In Humans
Funder
National Health and Medical Research Council
Funding Amount
$800,036.00
Summary
Blood stem cell transplantation is a vital therapy for patients with leukaemia following chemotherapy or for patients with bone marrow failure. Because many patients lack a donor, there is a need for an alternate source of stem cells, such as human pluripotent stem cells. During development, blood cells are formed from the blood vessel wall, or endothelium. In this project, we will study the regulation of this process in order to more efficiently make human blood cells in the laboratory.
Bone Marrow Endothelial Stem Cells Have The Capacity To Form Both The Endothelial And Haemopoietic Hierarchies
Funder
National Health and Medical Research Council
Funding Amount
$1,452,856.00
Summary
Blood cell formation is hierarchically organised; with hemopoietic stem cells (HSC) responsible for producing mature circulating blood cells. HSC reside in marrow near blood vessel cells. Although these play a key role in HSC regulation their origin in adults is poorly understood. We have demonstrated the existence of adult marrow vessel stem cells at the apex of a parallel hierarchy. Our objective is to characterise these in mice and humans and determine their role in blood malignancies.
Does Nuclear Reprogramming Of Granulocytes Induce Reversal Of The Hematopoiesis Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$461,805.00
Summary
Generation of induced pluripotent stem cells has enormous therapeutic potential. However, it is unclear whether de-differentiation to pluripotency proceeds via a reversion of the same developmental pathway that gave rise to the cell type being reprogrammed. To answer this we will dissect the reprogramming process within the well defined hematopoietic system and assess the generation of hematopoietic precursor-like cells during reprogramming.