Targeting Nerves In Tumours To Enhance Anti-cancer Immunity
Funder
National Health and Medical Research Council
Funding Amount
$1,090,190.00
Summary
The cancer journey is an incredibly stressful experience for patients. We discovered that stress stops immune cells and helps cancer spread. The goal of this study is to reveal how stress signals alter anti-cancer immunity and impacts cancer treatments. We will use elegant tools from neuroscience and immunology to define if blocking stress helps the immune cells that kill cancer and explore how blocking stress can improve standard anti-cancer drugs, including chemotherapy and immunotherapy.
Harnessing Extracellular Matrix Remodelling By Cancer-Associated Fibroblasts To Increase T Cell Infiltration Of Solid Tumours
Funder
National Health and Medical Research Council
Funding Amount
$923,407.00
Summary
The ability of killer T cells to find and eliminate tumour cells is the basis for adoptive transfer immunotherapies, which thus far only work well with blood-borne cancers. There is limited success with solid tumours, which T cells do not readily infiltrate, notably because of remodelling by fibroblasts. We have discovered that T cells migrate in tunnels dug in the tumour matrix by fibroblasts. Here, we will harness this discovery to improve tumour infiltration and rejection of solid tumours.
Repurposing Thalidomide Derivatives To Augment Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$1,154,196.00
Summary
Immunotherapies are a revolutionary approach for cancer treatment, but most people with cancer do not respond to therapy. We have identified a new set of molecular switches that shutdown immune function and limit responsiveness to existing immunotherapies. Importantly, we have found a class of approved drugs that can block these immune 'off switches'. This proposal will test if these drugs could be repurposed as a novel treatment to amplify the efficacy of existing immunotherapies.
The Role Of LINE Encoded Natural Antisense Transcripts In Immune Regulation
Funder
National Health and Medical Research Council
Funding Amount
$934,853.00
Summary
Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. This proposal aims to utilize cutting edge genomic technologies to generate new knowledge about how the non-coding genome regulates the expression of protein coding genes in human autoimmune disease.
About one in eight known genetic disorders involve DNA alteration that activates a cellular quality control mechanism that disables the affected gene. This mechanism is more efficient in some individuals than others. It can influence disease outcomes and severity. We will engineer and apply tools and models to measure and manipulate this crucial cellular mechanism. This will allow us to predict disease severity as well as to intervene where a manipulation of this mechanism will be beneficial.
Discovering The Cell Of Origin For Rare Ovarian Cancers
Funder
National Health and Medical Research Council
Funding Amount
$599,438.00
Summary
Ovarian cancer has many different varieties, and even though they all grow at the ovary, for some types we don't know the cell where the cancer starts. Using novel sequencing methods, this study will find the tissue of origin for two rare subtypes. This finding will help us to develop appropriate pre-clinical models that we can use to test emerging cancer therapies. Identifying the cell of origin will provide key insights into early detection or even prevention of these rare but deadly diseases.
Exploiting Messenger RNA Export As A Novel Therapeutic Strategy To Treat Cancer
Funder
National Health and Medical Research Council
Funding Amount
$948,098.00
Summary
Novel therapies for cancers represent an area of unmet clinical need. We have identified a new biological pathway implicated in cancer, namely selective mRNA export. Compounds inhibiting other steps of the gene expression pathway are promising therapeutic candidates for cancer, yet mRNA export inhibitors do not exist. We propose to develop first-in-class inhibitors of mRNA export that selectively target transcriptionally addicted cancers with dysregulated RNA processing.
Reprogramming Human Fibroblasts Into Induced Trophoblast Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$889,064.00
Summary
We have been able to generate artificial human trophectoderm which is the tissue that creates the placenta. This will allow us to do research in how the genes control the fate of these cells without the need of human embryos or placenta. We anticipate that the derivation and characterising these cells will revolutionise placenta research, which in turn will contribute to the establishment of new therapies for placenta disease and infertility.
Hybrid Optical-electrical Stimulation For Precise Neural Stimulation
Funder
National Health and Medical Research Council
Funding Amount
$935,579.00
Summary
In world-first research, we have evidence that combining electrical stimulation with optical stimulation significantly and safely improves precision of neural activation for devices such as cochlear and retinal implants. In this proposal we will use gene therapy to make nerves responsive to light in pre-clinical animal models to establish proof of concept that hybrid stimulation will significantly improve outcomes for recipients of cochlear and retinal implants.
Repeat Expansions In Neurological Disease: Discovery, Interpretation And Enhanced Diagnostics
Funder
National Health and Medical Research Council
Funding Amount
$889,937.00
Summary
Identifying the mutation or genetic cause of disease in an individual is the first step in the provision of appropriate clinical care and treatment. This diagnostic process is being revolutionised through the ability to sequence the entire human genome in a time and cost effective manner. This project will enable identification of novel and known repeat expansion using whole genome sequencing, providing rapid diagnoses and better clinical care for individuals with neurogenetic disorders.