Architecture Of The Hendra Virus Nucleocapsid And Implications For Replication
Funder
National Health and Medical Research Council
Funding Amount
$342,108.00
Summary
Hendra virus causes sporadic fatal outbreaks in horses, which may result in human deaths through direct contact with infected animals. The unanticipated surge of Hendra cases since mid-2011, the broad host range of the virus and the discovery of other related viruses worldwide highlight the epidemic potential of hendra-related paramyxoviruses. To improve our preparedness against paramyxoviruses, this Project aims at determining the structure of the viral replication machinery.
Life needs energy. We breathe and eat to make the universal biological fuel adenosine triphosphate (ATP). We turn over our own body weight in ATP every day and imbalances in this process lead to severe disorders such as obesity, diabetes and heart disease as well as to ageing. For any real breakthroughs we need to understand the machinery behind biological energy conversion in molecular detail and this is what my laboratory is aiming to achieve.
Structural Basis Of The Transcription Of Housekeeping Genes
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
TFIID, which is a regulator of cell growth and proliferation, has been identified as a new cancer drug target. However, more information on TFIID's mechanisms of regulation is required before such drugs can be designed. This project will fill this gap in understanding and enable the development of new cancer therapies.
Bacterial Mechanosensitive Channels As Novel Targets For Antibacterial Agents
Funder
National Health and Medical Research Council
Funding Amount
$424,500.00
Summary
The focus of this research is the development of new antibiotics to combat bacterial antibiotic resistance. Since their discovery antibiotics have had a profound effect on the health and well being of mankind, providing ready effective treatment for otherwise intractable infections. Although pencillin was initially effective against a large range of infections by the 1950s it was apparent that some bacterial strains had become resistant to this antibiotic. Partially in response to this resistanc ....The focus of this research is the development of new antibiotics to combat bacterial antibiotic resistance. Since their discovery antibiotics have had a profound effect on the health and well being of mankind, providing ready effective treatment for otherwise intractable infections. Although pencillin was initially effective against a large range of infections by the 1950s it was apparent that some bacterial strains had become resistant to this antibiotic. Partially in response to this resistance new antibiotics such as streptomycin, chloramphenicol and tetracycline were developed. These new drugs were potent against both Gram-positive and Gram-negative bacteria. However, there were early signs that resistance to these drugs was also emerging. For example, in 1953, during a Shigella outbreak in Japan, a strain of the dysentery bacillus was isolated which was multi-drug resistant, exhibiting resistance to chloramphenicol, tetracycline, streptomycin and the sulfanilamides. Multidrug-resistance in pathogenic strains of bacteria has in the last decade presented an increasing problem in treatment of bacterial infections and diseases. In 1994 a Melbourne public hospital reported a new antibiotic resistant strain of bacteria. This bacterium was resistant to vancomycin (the antibiotic used when all others have failed) and is known as VRE or vancomycin resistant enterococcus. Now strains of golden staph resistant to all antibiotics have appeared. The re-emergence of tuberculosis (TB), which kills more than 3 million people annually and which is spreading rapidly throughout the world, is also a serious threat, particularly as many strains are now multi-drug resistant. New antibiotics are needed that overcome bacterial drug resistance. It is anticipated that this research will lead to new antibiotics by exploiting molecular components of bacteria that have only recently been identified.Read moreRead less
The Structural Basis For The Control Of Cardiac And Skeletal Muscle By The Troponin Complex
Funder
National Health and Medical Research Council
Funding Amount
$369,003.00
Summary
Many key physiological processes are controlled by large, multi-protein complexes. These molecular machines ensure that signals transmitted in the body are correctly interpreted and amplified so as to control key body functions. The Troponin protein complex is one such large multi-protein complex which is the switch used to control both heart and skeletal muscle contraction in the body. The Troponin complex responds to increasing cellular calcium levels, switching the muscle on at high calcium. ....Many key physiological processes are controlled by large, multi-protein complexes. These molecular machines ensure that signals transmitted in the body are correctly interpreted and amplified so as to control key body functions. The Troponin protein complex is one such large multi-protein complex which is the switch used to control both heart and skeletal muscle contraction in the body. The Troponin complex responds to increasing cellular calcium levels, switching the muscle on at high calcium. When calcium returns to its normal basal level, the Troponin complex switches the muscle off. Naturally occurring genetic errors can lead to the malfunction of the Troponin complex. This, in turn, can lead to severe and possibly fatal diseases of the heart and muscle systems. To gain an understanding of these molecular diseases, it is important to understand the structure, dynamics and function of the Troponin complex. This project will use a newly-developed magnetic resonance method to monitor changes in the Troponin structure as a function of calcium level. Each component of the Troponin complex will be labeled with magnetic tags, allowing the determination of both structure and dynamics of Troponin, both in solution and in active muscle fibres. The study will result in a molecular understanding of how the Troponin switch works. This will give great insight in how mutations result in cardiac and muscular diseases.Read moreRead less
Flaviviruses Must Come Of Age: Design Of Stable, Mature Particles By Structural Vaccinology
Funder
National Health and Medical Research Council
Funding Amount
$1,149,487.00
Summary
We have established a powerful toolset combining advanced structural biology and rapid virus engineering that allows us investigate the assembly of flaviviruses in novel ways. This project will integrate these approaches to investigate the role of new ligands that we have identified in the structure of medically-relevant flaviviruses including dengue virus and delineate a novel maturation path for flaviviruses, which will be used to design safer and more effective flavivirus vaccines.
Structure And Mechanism Of Activation Of The Mechanosensitive Ion Channel TACAN
Funder
National Health and Medical Research Council
Funding Amount
$997,537.00
Summary
We propose to determine the structure and mechanism of activation of TACAN, a recently identified ion channel that defines a novel and uncharacterised class of channels. TACAN is specifically involved in sensing mechanical pain and contributes to mechanosensitive currents in the pain-receptor type of neurons. Our studies will increase knowledge of this novel class of proteins that will allow for the future development of treatments for several chronic pain conditions including arthritis.
Antibiotic resistant bacteria cause life-threatening diseases and represent a major public health problem. Globally, drug-resistant infections currently cause over 500,000 deaths annually and this figure is projected to exceed 10 million by 2050. Venom peptides are a new avenue of antibiotic discovery. This proposal aims to define how these peptides interact with the cellular power generator, ATP synthase, to provide a basis for exploiting their potential to treat bacterial infections.
An Integrative Structural Biology Approach To Understanding The SAGA Transcriptional Master Regulator Implicated In Cancer And Development
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Stringent control of gene expression ensures the harmonious life of all human cells. Loss of this control leads to development of a chaotic genome, characteristic of diseased states such as cancer. In this proposal, we aim at capturing and understanding the first key steps of the mechanism that, if dysfunctional, leads to aberrant gene expression. We will use cutting-edge structural bio-imaging to answer questions of fundamental importance to human health and pathologies.