Design And Engineering Of Adnectins For Diagnosis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$803,152.00
Summary
This project aims to engineer a naturally-occurring human protein, called an adnectin, to produce molecules that are able to bind specific targets in the human body, and as such may be used in the diagnosis and therapy of a range of diseases.
Generating An Effective Vaccine Response Against The Intrinsically Unstructured Malaria Antigen Merozoite Surface Protein 2
Funder
National Health and Medical Research Council
Funding Amount
$678,774.00
Summary
The malaria surface protein MSP2 is a promising candidate for inclusion in a malaria vaccine, having shown evidence of protection in phase IIb studies. Our goals are to identify the structural basis for the differential induction of human immune responses to native and recombinant MSP2 and to utilise this information to generate an MSP2 vaccine able to evoke a more effective anti-malarial response.
Virus Vaccines That Ensure Preparedness Against Future Public Health Emergencies
Funder
National Health and Medical Research Council
Funding Amount
$862,061.00
Summary
In this proposal, we will utilize novel technology we have developed (the molecular clamp) to generate candidate subunit vaccines and therapeutic antibody treatments against four highly pathogenic viruses identified by the World Health Organization as requiring urgent R&D to prepare for future epidemics; Ebola virus, Middle East Respiratory Coronavirus, Nipah virus and Lassa fever virus. Resulting vaccines are expected to provide advantages including safety, efficacy, and thermal stability.
Plasmin is a complex enzyme that performs major roles in removal of blood clots, wound healing and in tumor metastasis. Here we will understand how plasmin function is regulated at the molecular level. These key insights will be of future use in the development of therapeutics targeting the plasmin system in cancer and clotting diseases.
STABILISING G PROTEIN-COUPLED RECEPTORS FOR DRUG DISCOVERY
Funder
National Health and Medical Research Council
Funding Amount
$628,140.00
Summary
Prescription drugs targeting human proteins called GPCRs are sold as effective treatments for many diseases. However, there are over 800 different types of GPCRs in the human body and only a small fraction is targeted by drugs, mainly because GPCRs are unstable and thus difficult to work with in the laboratory. We are applying newly developed technologies to engineer stabilised ?1-adrenoceptors, a class of GPCRs, for drug discovery against cardiovascular diseases, epilepsy and neurodegeneration
Detection And Manipulation Of Neuronal Activities With A Synthetic Optogenetic Activity-reporting Transcription System
Funder
National Health and Medical Research Council
Funding Amount
$391,012.00
Summary
Functional brain mapping is important for understanding mental illnesses such as depression, attention deficit hyperactivity disorders and post-traumatic stress disorders. Current techniques for functional brain mapping are limited and not suitable for large-scale studies. The proposed project will generate new tools that can be used to map activated neurocircuitry in laboratory model organisms and will enhance our ability to design effective treatments for mental illnesses.
EPIGENETIC REPROGRAMMING OF MALIGNANT BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$863,268.00
Summary
Poorly differentiated breast cancers are aggressive tumors, frequently resistant to chemotherapy and associated with high morbidity. Herein we propose the engineering of more selective therapeutic agents able to target the genes involved in cancer initiation and resistance to treatment. We aim to correct and reprogram the cancer cell genome in state that is similar to normal, not tumorigenic cells. This work will generate novel forms of treatment for cancers that are presently not curable.
Resolving And Targeting The Complex Molecular Mechanisms Underlying GPCR Signalling
Funder
National Health and Medical Research Council
Funding Amount
$1,071,370.00
Summary
Receptors are located on the surface of all human cells to allow our cells to respond to their environment. Over 30% of prescription drugs act through particular receptors called GPCRs, however effective drugs without side effects are difficult to develop because we do not have a deep understanding of how GPCRs transmit complex signals. In this proposal we seek to resolve the atomic-level details of GPCR signalling to assist in the development of better drugs for a diverse range of diseases.
Designer DNA-binding Proteins Targeting Methylated DNA For Research And Therapeutic Purposes
Funder
National Health and Medical Research Council
Funding Amount
$583,444.00
Summary
A number of human genes function to suppress the onset or progression of cancer. In cancer sufferers, these genes are often switched off. The aim of this project is to engineer designer protein molecules that will be able to switch these tumor suppressor genes on again in a selective manner. Because the switching off of tumor suppressor genes is common to all forms of cancer, the new technology created in this work will potentially benefit patients suffering from any of a wide range of cancers.
Role Of Hsp40 And Hsp70 In Huntingtin Misfolding, Oligomerization And Inclusion Assembly
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
Huntington disease results from a mutation that causes the Htt protein to become abnormally sticky and form toxic clusters in neurons. Cells have natural defences to clustering with proteins called chaperones, which are exciting therapeutic targets. This project will examine how chaperones defend against toxic Htt clustering with cutting-edge imaging technologies. The knowledge gained will aid in designing therapeutic strategies that stimulate the defence processes and suppress the clusters.