Understanding Novel Drug Binding Pockets At G Protein-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$425,538.00
Summary
Cell-surface proteins exhibit multiple secondary binding sites for which only synthetic drugs have been identified so far. My hypothesis is that these secondary binding sites are common to most proteins because they are primarily targeted by largely yet unidentified endogenously released molecules that can modify the biology of these proteins.
Targeting Adenosine Mediated Immunosuppression To Enhance CAR T Cell Activity
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
The use of white blood cells genetically engineered to eradicate cancer cells specifically has been a major breakthrough in cancer treatment. These cells (CAR T cells) are very effective in blood cancers, but do not currently work well in other cancers. This is due to the immune suppressing nature of the cancer environment. I propose to use strategies to overcome this by genetically reprogramming the CAR T cells to be resistant to suppression by the cancer and therefore be more effective.
LRH-1 is a protein that is inappropriately present in cancers of the breast and other tissues. It causes cancer cells to divide and multiply, and therefore it is important to block its activity. There are, however, no treatments available that block LRH-1. This proposal brings together a team of researchers with broad experience. We will use high throughput technologies to identify and characterize novel LRH-1 inhibitors, and demonstrate their efficacy in reducing the growth of cancer cells.
EAR2: A Novel Driver Of Breast Cancer Proliferation
Funder
National Health and Medical Research Council
Funding Amount
$725,476.00
Summary
Drugs that block oestrogen are effective breast cancer treatments, but many patients are resistant to their effects. This research addresses a protein known as EAR2, that is elevated in breast cancer tissue compared to normal breast. We hypothesise that EAR2 drives breast cancer cell proliferation, and will test this using cell lines and mouse models. We will validate EAR2 as a new therapeutic target, benefitting patients underserved by current hormone therapies.
Targeting Antigen To Clec9A On Dendritic Cell For Humoral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$744,624.00
Summary
Dendritic cells capture infectious organisms and display them to other immune cells to initiate immunity. The process of capturing organisms requires dendritic cells to express a variety of cell-surface receptors that detect components carried by infectious agents. Here we will examine the efficacy of attaching vaccine components to a targeting agent that binds one of these receptors with the aim of enabling dendritic cells to efficiently kick-start immunity against vaccine components.
Deciphering Signalling Pathways Regulating Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$407,402.00
Summary
Iron overload and anaemia are two of the most significant health problems affecting humans. Understanding how the body regulates iron levels is key to our understanding of these disorders and to the future development of new therapies. This research is aimed at understanding how a hormone produced in the liver called hepcidin that maintains iron balance is regulated. This research may lead to novel therapies aimed at correcting the iron balance in conditions of iron overload or anaemia.
The Role Of Dendritic Cells In Sexual Transmission Of HIV And Viral Reservoir Formation
Funder
National Health and Medical Research Council
Funding Amount
$654,296.00
Summary
This grant aims to determine the subsets of dendritic cells found in the different tissue of the anogenital tracts and to determine which ones play the key roles in HIV transmission. The relative ability of these cells to transfer the virus to activated T cells leading to productive infection and resting memory T cells leading to latent infection will be investigated. Finally the key receptors which mediate this process will be determined and strategies to block this transfer developed.
The Identification And Characterisation Of A New DNA Receptor
Funder
National Health and Medical Research Council
Funding Amount
$656,498.00
Summary
The immune system has evolved to fight disease-causing microbes. First, it has to recognize that an infectious agent has invaded. To do this we have developed many probes (receptors) that sense microbial products. Detecting microbial DNA is a critical alarm bell. However, distinguishing pathogen DNA from our own DNA is difficult because both look alike. We have identified a new receptor that helps us identify bacterial DNA and alerts the immune system to the imminent danger.
EphA3, A Novel Target For Leukaemia Stem Cell Therapy
Funder
National Health and Medical Research Council
Funding Amount
$616,992.00
Summary
Patients with acute myeloid leukaemia often respond to therapy, but many relapse due to “leukemic stem cells” (LSC), the few cells in the original leukaemia which survive therapy. We focus on a protein (EphA3) which sits on LSCs and helps them interact with their environment. Disrupting this interaction may make these cells vulnerable to therapy. We aim to determine the function of EphA3 on LSCs and optimise the therapeutic use of an antibody against EphA3 which is currently in clinical trial.
Innate Immune Signalling In Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$562,857.00
Summary
Tuberculosis (TB) is a major global health threat that causes 1.5 million deaths every year. This study will characterise a new molecular control mechanism that optimises the immune response to the bacteria that cause TB and determine how it contributes to controlling the infection. Such knowledge is essential to help improve patient management and develop better treatments for this devastating disease.