Assembly And Misassembly Of Mitochondrial Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Mitochondria are the powerhouses in our cells. They burn the carbon fuels we eat and store the energy by making ATP that is used for functions such as muscle contraction and triggering of nerves. Mitochondrial Complex I is a molecular motor that helps to make ATP. “Mitochondrial disease” is often seen when Complex I is not built properly and this results in early childhood death. In this project we will study how Complex I is built and how the mitochondria responds to assembly problems.
The Role Of Accessory Subunits And Assembly Factors In The Biogenesis Of Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$569,987.00
Summary
The mitochondrial respiratory chain produces most of the energy required for our cells to grow and function. Complex I is the first enzyme of this chain and its defects are the most prevalent cause of mitochondrial disease, which often results in infant fatality. Defects in complex I have also been associated with Parkinson's disease and oxidative stress. This study will provide important new information into how complex I is built and what goes wrong to cause disease.
Characterising Complex I Function And Dysfunction In Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The cells in our body produce energy in power plants called “mitochondria”. Mitochondrial disease affects 1 in 5000 live births. Currently there is no cure, but understanding how the genes mutated in mitochondrial disease work is an important step to finding one. Previous research relied on patient samples; however we will employ new technologies allowing us to rapidly model mitochondrial disease in a laboratory setting.
NDI1 Therapy For NADH-Ubiquinone Oxidoreductase Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$575,762.00
Summary
This study will test a new protein therapy that can act as a surrogate for a deficient or defective enzyme called Mitochondrial Complex 1. The deficiency occurs in newborns with defective genes for the proteins that form the enzyme. The defect causes metabolic malfunction in most organs, with patients needing specialist hospital and parental care, but there is no cure yet. We have successfully tested this in the lab but will now test this in our new animal model of the disease.
NOVEL REGULATORS OF CONNECTIVE TISSUE GROWTH FACTOR EXPRESSION AND BIOACTIVITY IN DIABETIC COMPLICATIONS
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
Diabetes mellitus is common in our community. It causes much premature death and loss of quality of life. Recent data from Australian studies show that ~7% of adults over 25 years, and ~20% of people aged over 65 have diabetes, and diabetes in both children and adults is increasing in Australia. A critical problem caused by diabetes, irrespective of its cause, is that blood glucose levels are higher than normal. High blood glucose contributes to much of the damage to body tissues and to the earl ....Diabetes mellitus is common in our community. It causes much premature death and loss of quality of life. Recent data from Australian studies show that ~7% of adults over 25 years, and ~20% of people aged over 65 have diabetes, and diabetes in both children and adults is increasing in Australia. A critical problem caused by diabetes, irrespective of its cause, is that blood glucose levels are higher than normal. High blood glucose contributes to much of the damage to body tissues and to the early death that can occur in diabetes. Unfortunately, given our current treatment methods, in only a small number of patients can glucose levels in the body be consistently controlled into the normal range. How does high blood glucose cause damage to the body and its different tissues? This is a complex process. One way that damage occurs is through an increase in some of the growth factors in the body. In diabetes, high blood glucose can increase the production of some growth factors in an uncontrolled way. In turn, these growth factors then cause tissue damage. One of the growth factors that can be increased by the high glucose in diabetes is called connective tissue growth factor, or CTGF. CTGF can cause scars to form in tissues, and it is increased in diabetes in humans. Through NHMRC sponsored post-doctoral research over the past four years, Dr Twigg has published findings showing pathways by which diabetes causes increases in CTGF, and ways in which CTGF then causes tissue scarring. The current grant proposal presents new data showing further novel pathways by which CTGF is activated by diabetes and ways in which CTGF causes scarring. The pathways involved will be studied in detail in the project. In addition, methods to block CTGF and its harmful effects in diabetes will be developed in this work. By controlling CTGF, it is envisaged that damage to tissues will be reduced, leading to improved quality and quantity of life for people who have diabetes.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100004
Funder
Australian Research Council
Funding Amount
$540,000.00
Summary
An automated 3D electron microscopy facility. An automated 3D electron microscopy facility: The aim of this project is to establish the next generation of electron microscopy facility, with a fully automated tool enabling 3D imaging. The automated serial section system incorporated in a scanning electron microscope circumvents the limitation of transmission electron microscopy, which provides unique insights into molecular structures and cell components at high resolution, however, the area and ....An automated 3D electron microscopy facility. An automated 3D electron microscopy facility: The aim of this project is to establish the next generation of electron microscopy facility, with a fully automated tool enabling 3D imaging. The automated serial section system incorporated in a scanning electron microscope circumvents the limitation of transmission electron microscopy, which provides unique insights into molecular structures and cell components at high resolution, however, the area and volume are limited in size to a few microns. This new type of microscope can image whole organisms and be used by non-electron microscopists. It will be housed in an open access facility and will meet a growing demand for 3D electron microscopy.Read moreRead less
Sugars in the real world: are cultured cancer cells a good model system for studying protein glycosylation? It is challenging to study errors in metabolism in human beings, so researchers use cells grown in the laboratory to understand disease processes. This project will determine if cultured cells accurately reflect the real changes to cell surface sugars that occur in all cancers, and the effect of these changes on the invasive properties of colon cancer cells.
Identifying genes controlling the regulatory and metabolic interactions between the energy organelles of the leaf. Plant energy metabolism underlies the synthesis of many important products in crops, and subtle changes in metabolism can enhance key plant traits, such as germination rates, early seedling vigour, biomass/yield, and tolerance to harsh environments. Furthering our understanding on the complex interplay of genes controlling energy metabolism and its impact on leaf function has potent ....Identifying genes controlling the regulatory and metabolic interactions between the energy organelles of the leaf. Plant energy metabolism underlies the synthesis of many important products in crops, and subtle changes in metabolism can enhance key plant traits, such as germination rates, early seedling vigour, biomass/yield, and tolerance to harsh environments. Furthering our understanding on the complex interplay of genes controlling energy metabolism and its impact on leaf function has potential outcomes for smart genetic manipulation either by classical breeding or genetic transformation. There are more than 10,000 genes of unknown function in plant genomes and this represents a tremendous untapped resource for future Australian R&D outcomes and insights from this research proposal will have application to all plant-based agriculture.Read moreRead less
Molecular control of embryonic diapause. Many species can halt growth of the early embryo (diapause). This project will use novel animal models and new proteomics techniques to clarify what signals from the uterus control diapause of the embryo. This may uncover new mechanisms for cell regulation that will be relevant to the biology of stem cells, cancer and reproductive technologies.