The effect of mitochondrial and nuclear-cytoplasmic variation on longevity, metabolism and stress resistance in Drosophila. Much research points to a major role of free radical damage in aging, thus the belief that antioxidants might be beneficial in delaying aging. Free radicals are mostly formed in the subcellular organelles which consume oxygen and produce energy, and this may be the major site of age-related damage. This project seeks to understand the degree to which variation among these ....The effect of mitochondrial and nuclear-cytoplasmic variation on longevity, metabolism and stress resistance in Drosophila. Much research points to a major role of free radical damage in aging, thus the belief that antioxidants might be beneficial in delaying aging. Free radicals are mostly formed in the subcellular organelles which consume oxygen and produce energy, and this may be the major site of age-related damage. This project seeks to understand the degree to which variation among these subcellular organelles affect free radical damage and aging, using the fruitfly Drosophila melanogaster as a model organism.Read moreRead less
Autophagic vacuole formation in mammalian skeletal muscle; role of FOXO proteins. Loss of muscle tissue is a hallmark of many common health problems including cancer, HIV-Aids and renal failure. Recently, we identified that a family of transcription factors termed the forkhead box class-O (FOXO) winged helix transcription factors are key regulators of both anabolic (building) and catabolic (wasting) signalling pathways. This project will investigate the molecular regulation of cell integrity by ....Autophagic vacuole formation in mammalian skeletal muscle; role of FOXO proteins. Loss of muscle tissue is a hallmark of many common health problems including cancer, HIV-Aids and renal failure. Recently, we identified that a family of transcription factors termed the forkhead box class-O (FOXO) winged helix transcription factors are key regulators of both anabolic (building) and catabolic (wasting) signalling pathways. This project will investigate the molecular regulation of cell integrity by FOXO proteins. Although very basic in nature, these projects will identify how FOXO proteins regulate muscle cell building and wasting and, therefore, present a potential therapeutic target for muscle wasting diseases, making this project highly significant.Read moreRead less
The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. ....The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. We anticipate that there will be patents that will ensue from the programme, which will be licensed to Australian interests, and contribute to the national revenue in the biotechnology and pharmaceutical sector.Read moreRead less
Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins ....Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins central to AD, including amyloid-beta, and their role in AD development. Upon completion of this project, we expect to better understand neural copper metabolism in health and in AD pathology, with outcomes directly applicable to therapeutic AD intervention.Read moreRead less
Testing the free radical theory of aging: do indicators of oxidative damage predict lifespan? Because of the Free Radical Theory of Aging, many millions of dollars are spent around the world on dietary antioxidants of unproven efficacy. Many millions of research dollars are spent providing support for this theory but few studies test it rigorously. The first major benefit of this research is worldwide; to refute, or to substantially enhance and focus the current support for the Free Radical Theo ....Testing the free radical theory of aging: do indicators of oxidative damage predict lifespan? Because of the Free Radical Theory of Aging, many millions of dollars are spent around the world on dietary antioxidants of unproven efficacy. Many millions of research dollars are spent providing support for this theory but few studies test it rigorously. The first major benefit of this research is worldwide; to refute, or to substantially enhance and focus the current support for the Free Radical Theory. This should help to rationalise and direct funding supplied to these areas. The second benefit is for Australia: aging is a fruitful area for research because of the high general public interest and for training because of its multidisciplinary nature, and funding in Australia is very low by international standards. Read moreRead less
Coordinating energy metabolism to enhance exercise capacity. Diet and exercise contribute to health and ageing productively whereas high caloric diets and sedentary life styles are deleterious. The enzyme AMPK regulates energy metabolism in response to diet and exercise and by studying it we expect to learn why diet and exercise are beneficial at the molecular level. This may allow the development of nutritional, exercise and drug strategies to enhance exercise capacity and well being during ....Coordinating energy metabolism to enhance exercise capacity. Diet and exercise contribute to health and ageing productively whereas high caloric diets and sedentary life styles are deleterious. The enzyme AMPK regulates energy metabolism in response to diet and exercise and by studying it we expect to learn why diet and exercise are beneficial at the molecular level. This may allow the development of nutritional, exercise and drug strategies to enhance exercise capacity and well being during ageing as well as suppress age onset diseases that include obesity diabetes cardiovascular disease hypertension and neurodegeneration.Read moreRead less
Systems therapeutics for metabolism: AMPK isoform specific drugs. Living cells have to maintain a steady balance between energy production and consumption in order to function properly. A key regulator of energy balance is an enzyme known as 5' AMP-activated protein kinase (AMPK), which regulates the burning and storage of fuels such as fat and sugars, in response to changes in energy demand. This project will provide a major advancement in our understanding of the regulation of AMPK at the mo ....Systems therapeutics for metabolism: AMPK isoform specific drugs. Living cells have to maintain a steady balance between energy production and consumption in order to function properly. A key regulator of energy balance is an enzyme known as 5' AMP-activated protein kinase (AMPK), which regulates the burning and storage of fuels such as fat and sugars, in response to changes in energy demand. This project will provide a major advancement in our understanding of the regulation of AMPK at the molecular level, and lay the foundations for the development of more effective drugs to treat energy balance disorders such as obesity and Type 2 diabetes. Furthermore, this proposal will contribute to enriching Australia's international profile and competitiveness in this important area of research.Read moreRead less
Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outl ....Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outlined will elucidate the process of mitochondrial outer membrane permeabilization, a critical event in cell death by apoptosis, and determine how to kill cells in which this event is blocked.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100859
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Phosphatidylserine: a regulator of muscle and mitochondrial biology? This project aims to characterise a novel pathway involved in regulating skeletal muscle mass through effects on mitochondrial function. This project will examine how degradation causes mitochondrial abnormalities leading to severe muscle wasting. This project is expected to advance understanding of how pathways interact, thus identifying novel mechanisms that impact on muscle structure and function. Understanding what makes mu ....Phosphatidylserine: a regulator of muscle and mitochondrial biology? This project aims to characterise a novel pathway involved in regulating skeletal muscle mass through effects on mitochondrial function. This project will examine how degradation causes mitochondrial abnormalities leading to severe muscle wasting. This project is expected to advance understanding of how pathways interact, thus identifying novel mechanisms that impact on muscle structure and function. Understanding what makes muscle vulnerable to atrophy is fundamental to developing strategies to counteract muscle wasting conditions. Methodologies developed will have broad application in the field of life sciences research.Read moreRead less
The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle ma ....The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle mass ensures international competitiveness, productivity and economic growth, and successful ageing, where maintaining muscle mass is essential.Read moreRead less