Role Of Common Genetic Variation Driving Single Cell Transcriptional Heterogeneity Across The Cardiomyocyte Lineage
Funder
National Health and Medical Research Council
Funding Amount
$882,698.00
Summary
In human tissues, most mature cells develop by differentiation from pluripotent stem cells. As they undergo differentiation, their transcriptional activity changes dramatically. Many of the genetic causes for these changes are unknown, which limits research in the use of stem cells for treating and modelling disease. This proposal addresses this problem with cardiac muscle cell differentiation by utilising recent developments in biotechnology that enables individual cells to be sequenced.
The Importance Of Superstars: Cell Numbers And Lineages In Enteric Nervous System Formation
Funder
National Health and Medical Research Council
Funding Amount
$561,717.00
Summary
All digestive functions are controlled by a nerve system in the gut wall, and it works without us thinking about it. This is a huge system rivalling the spinal cord in number of nerve cells. And it has may different types of nerve cells. It originates from a very few cells early in the embryo, about 200 times fewer than the spinal cord. How do the cells manage to divide enough to make this system, and how do they 'know' how to make the right types of nerve cells in the right places in the gut?
Differentiation And Fate In The Developing Sympathetic Ganglia
Funder
National Health and Medical Research Council
Funding Amount
$353,754.00
Summary
This project seeks to understand how a small number of founder cells can divide and differentiate into the myriad different types of cells that make up the mature nervous system. It uses modern genetic techniques to follow progenitor cells as they mature into mature neurons.
Development Of Techniques To Expand Enteric Neural Crest-stem/progenitor Cells And To Administer Them To The Human Neonatal Colon For Repair Of The Enteric Nervous System Deficiciency In Hirschsprung Disease.
Funder
National Health and Medical Research Council
Funding Amount
$664,820.00
Summary
Gastrointestinal tract function is controlled by nerves in the intestine. These are missing in a small segment of the colon in the serious birth defect Hirschsprung disease. Current treatment is surgical removal of the affected colon segment, but instead, it may be possible to use nerve stem cells to provide some functional recovery. In particular, we are facing two practical questions: How can we produce enough nerve stem cells? and: How can these nerve stem cells be emplaced in the colon wall?
Novel Cell Therapy For Hirschsprung Disease: From Patient IPS Cells To Large Animal Trials
Funder
National Health and Medical Research Council
Funding Amount
$1,011,764.00
Summary
In Hirschsprung disease the lower bowel has no nerve cells. It does not function so it is surgically removed but quality of life is poor. A new idea is to replace the missing cells with new ones. Human infants are very large so we will use new stem cell technologies to create large numbers of cells. We will use polymer chemistry to devise a method of getting the cells into such a large organ as the bowel, and trial these on a model, the piglet, which closely resembles in size the human baby.
Genetic Fate Mapping Of Mesenchymal Stem Cell Origins And Investigating Their Contribution To Developmental Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$611,525.00
Summary
Mesenchymal stem cells are a population of cells that reside in various organs in the body and are thought to contribute to tissue repair. However little is known about the developmental origins and identity of these cells. I will investigate where these cells originate from, their molecular identity and how they relate to blood development. These findings will help in developing protocols to manipulate these cells to repair damaged organs. This study will also inform current attempts to generat ....Mesenchymal stem cells are a population of cells that reside in various organs in the body and are thought to contribute to tissue repair. However little is known about the developmental origins and identity of these cells. I will investigate where these cells originate from, their molecular identity and how they relate to blood development. These findings will help in developing protocols to manipulate these cells to repair damaged organs. This study will also inform current attempts to generate blood stem cells.Read moreRead less
Microparticles In NASH: Origins, Pathogenic Roles, And Biomarker Of Disease Activity
Funder
National Health and Medical Research Council
Funding Amount
$540,633.00
Summary
30% of Australians have non-alcoholic fatty liver disease (NAFLD). Cirrhosis is the third cause of death; only 10-25% of NAFLD livers show steatohepatitis (NASH), which leads to cirrhosis. We have found that microparticles (MPs), small fragments of cell membranes, circulate in NASH but not in ordinary fatty liver. We will now explore ways in which MPs incite inflammation and liver fibrosis in NASH, and design new tests based on MPs to improve clinical assessment of patients with NAFLD/NASH.
Development Of Functional Liver Tissue Engineered From Murine Hepatocyte Or Liver Progenitor Cell Spheroids To Correct Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$459,482.00
Summary
Many patients suffering from severe liver disease require a liver transplant, but due to a shortage of liver donors, many die prior to liver transplantation. This study investigates novel methods of growing liver tissue from mature liver cells called hepatocytes, or, liver stem cells implanted in a plastic chamber in mice with acute and chronic liver disease. It is anticipated that new liver tissue will grow in the chamber, the mice will be cured, and that this technique can be translated to hum ....Many patients suffering from severe liver disease require a liver transplant, but due to a shortage of liver donors, many die prior to liver transplantation. This study investigates novel methods of growing liver tissue from mature liver cells called hepatocytes, or, liver stem cells implanted in a plastic chamber in mice with acute and chronic liver disease. It is anticipated that new liver tissue will grow in the chamber, the mice will be cured, and that this technique can be translated to humans with liver disease.Read moreRead less
Cellular Therapy For Genetic Liver Disease Exploiting Induced Pluripotent Stem Cells And Liver Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$797,185.00
Summary
It has recently become possible to genetically reprogram mature cell types in the body to become stem cells and then redirect them to become any other cell type desired. This technology has immense, but as yet unrealised, diagnostic and therapeutic potential. In this project we seek to develop cellular therapies for metabolic liver disease. Specifically, we plan to generate liver cells from skin cells and to test the therapeutic effectiveness of these cells by curing liver disease in mice.
Physiologically-based Pharmacokinetics And Pharmacodynamics Of Therapeutic Stem Cells For Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$848,710.00
Summary
This project focuses on the challenging area of effective and optimal dosing cell-based therapy for liver diseases. We will investigate the fate and therapeutic effects of natural, modified and artificial therapeutic cells in the body and in liver regions using a physiologically-based kinetic model. Our key goal is advance cell therapy by providing a better understanding and dosing guidelines.