Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a fra ....Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a framework to test regulatory network models and to analyse the molecular basis of interactions between control systems. This research will eventually provide the ability to predict how cells respond to drugs and other environmental stimuli.Read moreRead less
How sexually antagonistic genes and sexual selection influence the evolution of the Y chromosome. Sexually antagonistic genes are beneficial to members of one sex, but costly to the other. They are of significance both to the coevolution between the sexes and the evolution of the sex chromosomes. We will measure the sexually antagonistic effects of genes that make male guppies sexually attractive. We will then study how these genes, and the process of sexual selection that favours them influence ....How sexually antagonistic genes and sexual selection influence the evolution of the Y chromosome. Sexually antagonistic genes are beneficial to members of one sex, but costly to the other. They are of significance both to the coevolution between the sexes and the evolution of the sex chromosomes. We will measure the sexually antagonistic effects of genes that make male guppies sexually attractive. We will then study how these genes, and the process of sexual selection that favours them influence the process of recombination between the X and Y chromosomes.Read moreRead less
Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking stru ....Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking structural biology approaches to solve difficult technical problems will foster collaborations within Australia and with leading laboratories abroad, providing excellent up-to-date research training for students and postdoctoral researchers.
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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.
Choosing when to be sexual: clonal and sexual reproduction in a population of honey bees. Sex is costly. There is the cost of finding a mate and the genome of offspring must be shared with the mating partner. Despite these costs, sex is common in animals, so the benefits of sex must be substantial. Benefits may include the prevention of inbreeding and generating variable offspring. Exploring the trade off between sex and cloning requires a model system where individuals can choose to reproduce ....Choosing when to be sexual: clonal and sexual reproduction in a population of honey bees. Sex is costly. There is the cost of finding a mate and the genome of offspring must be shared with the mating partner. Despite these costs, sex is common in animals, so the benefits of sex must be substantial. Benefits may include the prevention of inbreeding and generating variable offspring. Exploring the trade off between sex and cloning requires a model system where individuals can choose to reproduce sexually or asexually. This project will explore a population of honey bees where a genetic mutation allows queens to clone themselves or reproduce sexually. We will reveal the unusual genetic mechanisms behind this ability and show how they are used by queens and workers to increase their reproductive success.Read moreRead less
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.
Elucidation of the signalling pathways during fertilization in mammals. This grant sets out to understand how the union of the sperm and egg at fertilization generates a viable embryo: this is a fundamental event in biology. We aim to understand the basic signalling pathways from the sperm which allow the egg to become an embryo and are known to influence embryo quality. They are therefore important in our understanding of what constitutes a healthy early start to life. Australia also has econom ....Elucidation of the signalling pathways during fertilization in mammals. This grant sets out to understand how the union of the sperm and egg at fertilization generates a viable embryo: this is a fundamental event in biology. We aim to understand the basic signalling pathways from the sperm which allow the egg to become an embryo and are known to influence embryo quality. They are therefore important in our understanding of what constitutes a healthy early start to life. Australia also has economic interests in understanding the reproductive process in aiding breeding programs for commercially important livestock and endangered species and contraception programs for pest populations. Read moreRead less
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
Pressures Exerted On Upper Airway Walls By Surrounding Tissue Structures
Funder
National Health and Medical Research Council
Funding Amount
$426,500.00
Summary
The obstructive sleep apnoea syndrome (OSA) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSA effects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in 5% of men over the age of 45 years. In the proposed studies we will examine the effect of the pressure in the tissues surrounding the throat on the ability of the throat to stay open a ....The obstructive sleep apnoea syndrome (OSA) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSA effects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in 5% of men over the age of 45 years. In the proposed studies we will examine the effect of the pressure in the tissues surrounding the throat on the ability of the throat to stay open and allow breathing. The major outcome of the animal studies is increased knowledge concerning mechanisms whereby collapsing forces are applied to the upper airway. This will give insights into potential factors influencing upper airway collapse during sleep in OSA patients. Of particular importance will be our studies on the effects of jaw position on the pressure exerted on the walls of the throat since the use of an intra-oral device to hold the jaw forward during sleep is one of the treatments used to prevent throat blockage during sleep. The studies in humans will examine, for the first time, the notion that the mass (weight) of the neck has a direct effect on the severity of sleep disordered breathing. If neck mass has a substantive influence on sleep disordered breathing then strategies aimed at reducing neck mass (fat) may provide a new therapeutic approach to the management of OSA patients.Read moreRead less