Combating Bacterial ‘superbugs‘ By Innovative Dosing Strategies That Combine Available Antibiotics To Prevent Resistance
Funder
National Health and Medical Research Council
Funding Amount
$547,694.00
Summary
As resistant bacterial ‘superbugs’ are among the 3 most serious threats to global health and as new antibiotics are lacking, innovative strategies to prevent bacterial resistance are urgently needed. This proposal will yield molecular insights on optimal combinations of current beta-lactam antibiotics to maximise bacterial killing without resistance. This project will provide guidance to physicians on how to optimally combine available beta-lactam antibiotics to prevent bacterial resistance.
Making Human T- And B-lymphocytes For Immunotherapy And Antibody Production
Funder
National Health and Medical Research Council
Funding Amount
$795,880.00
Summary
Lymphocytes are white blood cells that are involved in producing antibodies, killing defective cells, or killing cells infected with viruses. In recent years, researchers have found ways to harness lymphocytes to develop medicines for treating a variety of different cancers. In this project, we will establish methods to make human lymphocytes in the laboratory from stem cells, paving the way for the broader application of this cell type to new therapies.
Leveraging Genomics Strategies To Generate Adult Neurons From IPSCs And Somatic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,593,336.00
Summary
Recent advances have made it possible to derive myriad specialized human cells from stem cells or by directly reprogramming cell identity. However, these derived cells are generally arrested at a fetal developmental stage, and do not mature to function like adult cells. We will use new genomic, epigenetic, cell reprogramming, and manipulation methods to discover how to derive mature cells, aiming to generate mature neurons for use in neurobiology research, disease modeling, and drug screening.
Transcriptional Effectors Of Oncogenic ERK Signaling In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$820,776.00
Summary
This project aims to unravel how one of the most frequently deregulated molecular pathways in colorectal cancer controls the expression of genes required for these tumours to grow and spread. We expect this work to uncover novel therapeutic targets to effectively inactivate this pathway and biomarkers to select patients most likely to benefit from existing therapies.
Fellowship Application, Ed Stanley: Pluripotent Stem Cells & Medical Research
Funder
National Health and Medical Research Council
Funding Amount
$638,517.00
Summary
Human Pluripotent Stem Cells are immortal cells that have the ability to turn into any of the cell types found in the body. This means that it is now possible to generate a variety of human cell types in the laboratory, to study how they work, and to find out what goes wrong in different diseases. In this context, the overall aim of my research is to develop pluripotent stem cells for the study of human disease and generate tools that will enable others to use these cells in their own research.
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.
Migration And Differentiation Of Enteric Neuron Precursors
Funder
National Health and Medical Research Council
Funding Amount
$385,116.00
Summary
There are many millions of nerve cells within the wall of the intestine, and they control many intestinal functions, including motility. During development, these nerve cells arise from cells which migrate away from the developing brain and first enter the stomach. The migratory cells are called neural crest cells. After entering the stomach, neural crest cells migrate within the wall of the gastrointestinal tract, until they reach the far (anal) end. In embryonic mice, this colonisation of the ....There are many millions of nerve cells within the wall of the intestine, and they control many intestinal functions, including motility. During development, these nerve cells arise from cells which migrate away from the developing brain and first enter the stomach. The migratory cells are called neural crest cells. After entering the stomach, neural crest cells migrate within the wall of the gastrointestinal tract, until they reach the far (anal) end. In embryonic mice, this colonisation of the entire small and large intestines by neural crest cells takes over 4 days, and in humans the process probably takes at least one week. It is essential that the neural crest cells colonise the entire gastrointestinal tract, since regions of intestine lacking neural crest cells (and hence nerve cells) cannot function and intestinal contents build up in front of the region lacking nerve cells. This condition is found in some babies (Hirschsprung's disease), and it can only be treated by surgically removing the region lacking nerve cells. It is therefore essential that migratory neural crest cells colonise the entire gastrointestinal tract. Currently, little is known about the mechanisms controlling the migration of neural crest cells, and whether a) particular molecules within the gut wall are important for migration, and-or b) the migratory behaviour of the neural crest cells is regulated mostly by the neural crest cells themselves. In this study we will take time-lapse images of neural crest cells migrating through the gut of embryonic mice to identify the factors that are important for the migration. After the neural crest cells have colonised the entire intestine, they develop into different types of nerve cells. We will also examine some of the factors affecting the development of different types of nerve cells.Read moreRead less
Control Of Human ? Cell Differentiation And Function
Funder
National Health and Medical Research Council
Funding Amount
$616,979.00
Summary
Diabetes is a condition in which the body is unable to regulate the level of glucose in the blood. Blood glucose is normally controlled by a particular cell type, the beta cell, which is found in the pancreas. In diabetes, this cell is either missing or does not function correctly. This project will produce human beta cells in the laboratory that can be used to find out what goes wrong in diabetes.
A Suite Of Engineered Human Pluripotent Stem Cell Lines To Facilitate The Generation Of Hematopoietic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$881,221.00
Summary
Our goal is to develop tools that address major bottlenecks that have prevented the generation of blood forming stem cells in culture for therapeutic use. We will generate human embryonic stem cell reporter lines that can be used to monitor key milestones in blood stem cell development. These lines will serve as tools to identify growth conditions to improve the differentiation of pluripotent stem cells to functional blood stem cells.
Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less