Investigation Of Molecular And Cellular Determinants Of Immune Related Adverse Events Following Treatment With Immune Checkpoint Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Novel immune-based treatments for advanced, incurable, cancer have significantly improved patient survival. Although these treatments have proven highly effective, they are associated with the unpredictable development of severe and sometimes life-threatening autoimmune disease. We aim to discover ways to predict and potentially prevent these complications by identifying genetic risk factors and markers in blood samples. If successful, this will be a ground breaking advance in cancer care.
A DENDRITIC SUBSTRATE FOR THE CHOLINERGIC CONTROL OF NEOCORTICAL OUTPUT
Funder
National Health and Medical Research Council
Funding Amount
$898,340.00
Summary
The forebrain cholinergic system controls neocortical activity and cognitive function. This project will investigate the mechanisms by which the cholinergic system controls neocortical circuit activity in rodent models using advanced optical and electrical recording methods. The results will provide a foundation for the understanding of how dysfunction of the cholinergic system results in cognitive decline in humans, and identify new targets for improved treatment of human cognitive impairment.
Cellular Microenvironments Facilitating The Replication And Propagation Of Flaviviruses
Funder
National Health and Medical Research Council
Funding Amount
$505,279.00
Summary
Flaviviruses are the agents of many mosquito-transmitted infections and many deaths globally each year. The emerging virus West Nile virus (strain New York) is a member of this virus family and shares 99% amino acid homology with the endemic Australian virus Kunjin virus. During virus growth in cells, cellular membrane structures are induced or rearranged by these viruses for their own purpose. That being the production of more virus particles for reinfection of other cells. Using Kunjin virus a ....Flaviviruses are the agents of many mosquito-transmitted infections and many deaths globally each year. The emerging virus West Nile virus (strain New York) is a member of this virus family and shares 99% amino acid homology with the endemic Australian virus Kunjin virus. During virus growth in cells, cellular membrane structures are induced or rearranged by these viruses for their own purpose. That being the production of more virus particles for reinfection of other cells. Using Kunjin virus as a model, and advanced techniques in biochemistry and electron microscopy, we have identified for the first time these membrane structures as the apparent sites of replication of the viral RNA or genetic material, and of the viral proteins involved. We have also observed how new virus particles are able to get out of infected cells and shown how some drugs can prevent this occurring thus limiting their transmission. This research will focus on how the membrane structures are formed in infected cells. The research will determine what cellular components are required by the virus to help it propagate. In particular specific cellular proteins and membrane components that are captured by the virus and moved to different sites in the infected cells. These apparent requirements could possibly lead us to a greater understanding of the complex interactions that occur between the invading virus and the host cells. We aim to directly visualize the process of infection within living cells using new and innovative microscopic techniques. Another of our objectives is to determine the effects of infection on normal cells. The question being whether flavivirus infection disrupts normalcell fuctions like secretion etc. An understanding of these processes, and how the viral RNA is copied into new RNA for more virus particles, will assist in the development of antiviral drugs for treatment of this pathogenic group of viruses.Read moreRead less
Exploiting And Defining The Immune Regulatory Activities Of BET Bromodomain Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Immune-based agents such as “checkpoint inhibitors” have the ability to re-awaken our own immune systems and activate previously dormant anti-tumour responses. We have discovered that small molecule inhibitors of gene regulatory proteins called bromodomain proteins act synergistically with checkpoint inhibitors in mouse cancer models. I will define the molecular and biological events underpinning this novel combination approach and assess the effects of the combination across different tumours.
Antibiotic Conjugates: Joining Together To Fight Antimicrobial Resistance
Funder
National Health and Medical Research Council
Funding Amount
$697,675.00
Summary
New strategies are urgently needed to treat the rise of infections from multidrug-resistant bacteria, with standard antibiotic therapies becoming obsolete. This project will develop multiple innovative approaches to overcome antibiotic resistance, based on a core concept of appending additional functionality to existing antibiotic scaffolds. New conjugates will be synthesized, tested for antimicrobial activity, then optimized via a validated antimicrobial development pipeline.
Treating Metastatic Melanoma With Stereotactic Ablative Body Radiotherapy And IMmune Pathway ACTivation (SABR-IMPACT)
Funder
National Health and Medical Research Council
Funding Amount
$185,445.00
Summary
Metastatic melanoma has historically had extremely poor survival. Drugs that activate the immune system provide some hope, and in the minority who respond survival beyond 10 years is possible. Radiotherapy causes local tumour death resulting in antigen exposure and systemic effects that may also stimulate the immune system. The combination of radiotherapy and immune activating drugs may be synergistic and result in improved survival for a greater proportion of patients.
Multi-centre, Multi-disciplinary Study Using A Systems Biology Approach To Investigate Immunomodulation In Children With Acute Wheeze
Funder
National Health and Medical Research Council
Funding Amount
$1,895,107.00
Summary
The concept that immunomodulation using naturally-occurring bacterial agents can treat asthma has reached international prominence. This is backed by strong epidemiologic and clinical trial data. However, detailed knowledge of the immunological mechanisms involved is essential to allow more focused therapeutic agents to be developed. The proposed multi-disciplinary immunomodulation study in 200 children aims to provide this essential information using an advanced systems biology approach.