Transgenerational Effects Of Male Obesity - Mechanisms And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$829,143.00
Summary
Childhood obesity is associated with obesity in either parent, and obese children tend to become obese adults, forming an intergenerational cycle that promotes obesity. We have identified paternal obesity as an important novel target for intervention to stop the progression of the obesity epidemic. This project investigates supplementation of obese fathers with folate to prevent the adverse impact of paternal obesity on subsequent generations.
We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Deadly Commute - Targeting The Trafficking Mechanisms That Licence Inflammatory Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$774,544.00
Summary
MLKL is a protein naturally found inside cells. MLKL is activated by inflammation. Once activated, MLKL relocates to the outer periphery of cells and kills them. Gut cells are especially vulnerable to death-by-MLKL and this problem causes Inflammatory Bowel Disease. Using cutting edge microscopy, we have discovered how MLKL moves to the periphery of cells prior to killing them. We will test if blocking this movement of MLKL to the cell periphery stops gut death and Inflammatory Bowel Disease.
Touch and Tension: Molecular Determinants of Human Mechanosensation . Feelings of touch and muscle tension are initiated by mechanosensory neurons found within the peripheral nervous system. Knowledge of human mechanosensory neurons has predominantly relied on rodent studies because of the limited availability of human tissue, which is not ideal. Our team has developed novel technologies for generating human mechanosensory neurons ‘in the dish’. The major aim of this project is to use human stem ....Touch and Tension: Molecular Determinants of Human Mechanosensation . Feelings of touch and muscle tension are initiated by mechanosensory neurons found within the peripheral nervous system. Knowledge of human mechanosensory neurons has predominantly relied on rodent studies because of the limited availability of human tissue, which is not ideal. Our team has developed novel technologies for generating human mechanosensory neurons ‘in the dish’. The major aim of this project is to use human stem cell-derived mechanosensory neurons as a platform to extensively study their molecular and functional properties. The significant benefits are the advancement of knowledge in the human mechanosensory system, which to date has been lacking, and in the long-term progress commercial development of novel drugs.Read moreRead less
Pathogenesis Of Persistent Human Virus Infections Of Global Significance
Funder
National Health and Medical Research Council
Funding Amount
$6,571,328.00
Summary
The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully ....The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully persist within reservoirs in the human body. The research program brings together a group of 6 leading scientists and clinicians located at 3 sites in 2 Australian cities. The team is comprised of experts in the study of HIV-AIDS, cytomegalovirus and herpes simplex virus who will combine their knowledge and expertise to speed up the process of research on these viruses that are of major health importance. Studies will also utilise a number of cutting edge technologies that now make it possible to much more rapidly and precisely determine how viruses cause disease. Advances in our understanding of how viruses persist may form the basis for treatments aimed at controlling persistent infections and the serious diseases caused by these viruses.Read moreRead less
Targeting Drug-Resistance In Paediatric Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$649,048.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease, particularly for patients that develop drug-resistance such as those at the time of relapse.
Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad ra ....Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad range of traits including metabolism, biofilm formation, antibiotic tolerance, and virulence. The work proposed here will enhance our ability to predict and control bacterial gene expression with potential future impacts on bioproduction, synthetic biology, and veterinary and medical microbiology.Read moreRead less
Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the pr ....Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the proposed project is to elucidate these important aspects of circRNA biogenesis. Specifically, the project aims to (a) discover proteins that regulate circRNA expression, (b) elucidate how circRNA expression interacts with alternative splicing, and (c) identify circular RNAs that play regulatory roles in gene expression. Read moreRead less
How does the noncoding genome regulate gene expression in the human brain? The non-coding genome is recognized as a major player in orchestrating gene expression in higher eukaryotes. This project aims to identify regions of the human genome that are important for gene expression during neuronal differentiation and depolarisation (i.e. neural enhancers), and to investigate their evolutionary properties. The roles of non-coding DNA in regulating the dynamic gene expression patterns underlying com ....How does the noncoding genome regulate gene expression in the human brain? The non-coding genome is recognized as a major player in orchestrating gene expression in higher eukaryotes. This project aims to identify regions of the human genome that are important for gene expression during neuronal differentiation and depolarisation (i.e. neural enhancers), and to investigate their evolutionary properties. The roles of non-coding DNA in regulating the dynamic gene expression patterns underlying complex human brain functions remains to be elucidated. By combining transcriptome quantification and bioinformatics methods, this project will close an important knowledge gap in our understanding of transcriptional regulation underlying human brain function. This will provide benefits such as the potential to influence public health policy including in cognitive functions and aging.Read moreRead less