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
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.
Understanding The Role Of The Atypical Cadherin Fat4 In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$1,006,248.00
Summary
This application will define the role of a large cell adhesion molecule, FAT4, in lymphatic vascular development. By understanding how FAT4 functions in lymphatic vessels, we will gain insight to the mechanisms by which mutations in the gene that encodes this protein cause a human lymphoedema syndrome.
Regulation Of T Cell Effector Function In Peripheral Tissues
Funder
National Health and Medical Research Council
Funding Amount
$698,550.00
Summary
Protection from infections relies on different types of immune cells. While some of these cells are found in the blood, others reside in peripheral tissues such as the skin. We will analyse the function of these peripheral immune cells to understand how they work to fight off infections. We will also investigate how so-called memory cells that permanently reside in peripheral tissues can protect from re-infection with similar bacteria or viruses.
The Role Of Clathrin In The Spindle Assembly Checkpoint And As An Anti-cancer Target
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
Cell division produces two daughter cells. Incorrect localisation and modification of proteins that regulate mitosis cause errors that can lead to cancer. As well as using a unique machinery mitosis uses proteins involved in non-cell cycle pathways. This project investigates the role during mitosis of one such protein: clathrin. We will identify lead clathrin inhibitory compounds, pitstops, that have potential anti-cancer properties, ultimately to be used as a chemotherapy agent.