EPIGENETIC REPROGRAMMING OF MALIGNANT BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$863,268.00
Summary
Poorly differentiated breast cancers are aggressive tumors, frequently resistant to chemotherapy and associated with high morbidity. Herein we propose the engineering of more selective therapeutic agents able to target the genes involved in cancer initiation and resistance to treatment. We aim to correct and reprogram the cancer cell genome in state that is similar to normal, not tumorigenic cells. This work will generate novel forms of treatment for cancers that are presently not curable.
A Biologically Responsive and Anatomically Authentic Human Nasal Model. As respiratory conditions caused by pollutants and viruses become more prevalent, human nasal models to study infection/protection mechanisms and nasal drug/vaccine delivery are increasingly important. This project aims to develop a world-first human nasal model to mimic both anatomical and biological aspects of the nasal cavity and predict the distribution and deposition of fine particles and the resultant biological respon ....A Biologically Responsive and Anatomically Authentic Human Nasal Model. As respiratory conditions caused by pollutants and viruses become more prevalent, human nasal models to study infection/protection mechanisms and nasal drug/vaccine delivery are increasingly important. This project aims to develop a world-first human nasal model to mimic both anatomical and biological aspects of the nasal cavity and predict the distribution and deposition of fine particles and the resultant biological response from the nasal mucosa. The aim is to overcome a key fabrication challenge - to 3D print an anatomically accurate nasal construct with a porous wall on which to grow and mature functional nasal tissue that lines a nasal cavity wall. The benefit would be enabling faster development of more targeted drugs and vaccines.Read moreRead less
Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that ....Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that have identified the earliest marker of endocardial differentiation and devised the method to make endocardium from stem cells. Knowledge from this work will inform future research into growing and regenerating damaged tissue.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family protei ....Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This project will address a new paradigm in genetics that is likely to underpin development.Read moreRead less
Controlling the adhesome to regulate cell fate on biomaterials. Mesenchymal stem cell-based tissue engineering practices are hampered worldwide by the lack of appreciation and understanding of the matrix-mediated cues that must be provided during adhesion and spreading to drive cells to definitive tissue end points. This project will address these knowledge deficiencies by combining high throughput array technologies, a set of tailorable self-assembling biomaterials and real-time biosensors to r ....Controlling the adhesome to regulate cell fate on biomaterials. Mesenchymal stem cell-based tissue engineering practices are hampered worldwide by the lack of appreciation and understanding of the matrix-mediated cues that must be provided during adhesion and spreading to drive cells to definitive tissue end points. This project will address these knowledge deficiencies by combining high throughput array technologies, a set of tailorable self-assembling biomaterials and real-time biosensors to rapidly, at high resolution, elucidate how mechanotransductive cues determine the fate choice of mesenchymal stem cells, and furthermore, how to manipulate them with smart biomaterial design to achieve desired outcomes for tissue engineering. Read moreRead less
Bone tissue engineering using innovative tubular dual-layered nanofiber meshes. Lifetime risks for long-bone fractures in Caucasians over the age of 50 are 17 per cent for women and 6 per cent for men. A clear therapeutic need exists to address the ever-increasing problems of diminished productivity and reduced quality of life associated with bone disorders as the population ages. To address this challenge, the project’s multidisciplinary, international team will develop technologies to heal tib ....Bone tissue engineering using innovative tubular dual-layered nanofiber meshes. Lifetime risks for long-bone fractures in Caucasians over the age of 50 are 17 per cent for women and 6 per cent for men. A clear therapeutic need exists to address the ever-increasing problems of diminished productivity and reduced quality of life associated with bone disorders as the population ages. To address this challenge, the project’s multidisciplinary, international team will develop technologies to heal tibial defects. Furthermore, it will establish Australia's prominence in the tissue engineering field, training the next generation of young scientists and engineers. This technology will be of interest to numerous research groups and companies worldwide and will foster international collaboration, placing Australia at the forefront of this emerging field.Read moreRead less
Special Research Initiatives - Grant ID: SR1101002
Funder
Australian Research Council
Funding Amount
$21,000,000.00
Summary
Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and ....Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and the ability to control and influence this process. Stem Cells Australia will deliver new methods for stem cell propagation and manipulation, new translational technologies for therapeutic applications, and will prepare Australia’s future stem cell scientific leaders.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC190100026
Funder
Australian Research Council
Funding Amount
$4,969,663.00
Summary
ARC Training Centre for Cell and Tissue Engineering Technologies. The ARC Training Centre for Cell and Tissue Engineering Technologies aims to provide training to create a highly skilled workforce for the tissue engineering and regenerative medicine sector and to enhance research performance and innovation in Australia through fundamental and applied research carried out in industry-led PhD projects. The research aims to address major aspects of the manufacturing and commercialisation pathway an ....ARC Training Centre for Cell and Tissue Engineering Technologies. The ARC Training Centre for Cell and Tissue Engineering Technologies aims to provide training to create a highly skilled workforce for the tissue engineering and regenerative medicine sector and to enhance research performance and innovation in Australia through fundamental and applied research carried out in industry-led PhD projects. The research aims to address major aspects of the manufacturing and commercialisation pathway and barriers faced by the sector, namely improving process efficiencies, enabling early-stage scale-up (cell/tissue) and development of the sector's supply chain. The knowledge created and research undertaken would help to accelerate commercialisation in regenerative medicine, tissue engineering and cell therapies.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100986
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
An innovative platform using non-coding ribonucleic acids (RNAs) to control stem cell differentiation outcomes. It is difficult to control the tissue type that stem cells will form when combined with biomaterials, as the outcome is influenced by the 'stiffness' of the surface to which the stem cells attach. This project will determine how non-coding ribonucleic acids (RNAs) control stem cell behaviours and use this information to direct stem cell differentiation outcomes.