Understanding The Role Of The Scaffolding Protein D13 In Poxvirus Assembly And Its Inhibition By Rifampicin
Funder
National Health and Medical Research Council
Funding Amount
$371,275.00
Summary
Smallpox is one the most notorious diseases in human history. Despite its eradication in the 1970s, human cases of animal poxviruses such as monkeypox virus and the potential use of smallpox as a bioterrorism weapon have called for an improved preparedness of Australia against (re)-emerging poxviruses. This project combines structural biology approaches to understand the complex assembly of poxviruses and provide the basis for the development of broad-spectrum antiviral drugs.
We know that many parts of viruses are displayed to the immune system, but infection can also result in the display of fragments of our body's own proteins (self-peptides). We will apply cutting-edge technology to find all the virus- and self-peptides that are recognised by the immune system during infection with a vaccine virus and influenza virus. This will help us understand how the body fights infection and perhaps why infection can sometimes start autoimmune diseases.
The Role Of Actin-based Motility As A Virulence Mechanism And Potential As An Antiviral Target
Funder
National Health and Medical Research Council
Funding Amount
$325,798.00
Summary
Our repertoire of effective treatments for infectious diseases is fast becoming exhausted as resistance to antibiotics and antivirals evolves and rapidly spreads throughout our community. We have developed a new paradigm in treating viral diseases that we predict will not give rise to resistance, and this project will be the first to demonstrate the effectiveness of this novel therapy in an endemic disease model.
Immunodominance In Vaccinia Virus And Recombinant Vaccinia Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$388,455.00
Summary
When confronted with an invading microbe, the human immune system does not recognise its overall shape. Instead, the microbe is chopped up into tiny fragments, called peptides, and these can be recognised by special cells of the immune system called T cells which orchestrate a response. We have a good understanding of this chopping process and can predict many of these peptides, but this is only part of the story. Not all peptides will be recognized by a T cell. Further, through processes we do ....When confronted with an invading microbe, the human immune system does not recognise its overall shape. Instead, the microbe is chopped up into tiny fragments, called peptides, and these can be recognised by special cells of the immune system called T cells which orchestrate a response. We have a good understanding of this chopping process and can predict many of these peptides, but this is only part of the story. Not all peptides will be recognized by a T cell. Further, through processes we do not understand well, T cells that recognize only a few out of the many peptides will dominate an entire immune response. As a result, immune responses are focused in such a way that they recognize only a tiny portion of an invading microbe. Focusing of immune responses also occurs during immunization with vaccines. Some new, genetically engineered vaccines use a harmless microbe to carry small parts of more dangerous pathogens. The parts chosen will not cause any disease by themselves, so the whole vaccine is safe. Vaccines built in this way are in clinical trials for diseases such as AIDS and malaria, but do not work as well as was hoped. These new vaccines are largely made up of the carrier and the parts of the microbe we wish to immunize against (e.g. a part of the AIDS virus) will be only a small fraction of the whole vaccine. Ideally we would like the immune system to focus on this small part of our choosing, but the few studies done suggest that this is not the case. In this project we will study vaccines that use a carrier called vaccinia virus. We will test to what extent immune responses are focused inappropriately. We will then genetically alter the virus and use new immunisation strategies to try and shift the focus of the immune response so that it targets the right parts of the vaccine. The ultimate aim is to improve vaccines, but in the process we may learn more about how the immune system chooses its targets.Read moreRead less