Epilepsy is one of the most common chronic neurological disorders; it affects 1% of the world’s population, yet about 1 in 3 patients fail to achieve seizure control with current drugs. We will improve the properties of small molecules (drugs) that specifically target the GTPase activity of the enzyme dynamin, to reduce seizure effect in the brain by a novel mechanism. We will optimize and pre-clinically test these future chemical entities as potential anti-epileptic drugs.
Predicting Drug-drug Interactions Due To Tyrosine Kinase Inhibitors: Inhibition Of Drug Metabolising Enzymes And Transporters
Funder
National Health and Medical Research Council
Funding Amount
$535,495.00
Summary
Tyrosine kinase inhibitors (TKIs) are a new class of anticancer agents. Cancer patients typically receive multiple drugs, for the treatment of cancer and other diseases, increasing the probability of interactions between coadministered drugs. Despite the widespread use of TKIs, their potential to cause drug interactions is poorly understood. Using novel in vitro approaches, this project will identify drug interactions precipitated by TKIs thereby improving drug efficacy and patient safety.
In 2013 there were ~200 million clinical cases of malaria, causing ~600,000 deaths. All antimalarial drugs are now associated with malaria parasite resistance. Thus, new therapies are urgently needed, including new drugs to prevent this disease. We have made the exciting discovery that an existing antimalarial drug can kill malaria parasites in a unique, previously unknown, manner. Here, we will investigate how this occurs and develop new drug candidates for malaria prevention.
Structure-based Design Of Novel Therapeutics For Multi-drug Resistant Neisseria Gonorrhoeae
Funder
National Health and Medical Research Council
Funding Amount
$669,148.00
Summary
Multiple drug resistance (MDR) in bacteria represents one of the most intractable problems facing modern medicine. The recent superbug, MDR-Neisseria gonorrhoeae (MDR-Ng), causes the sexually transmitted infection gonorrhoeae. A multi disciplinary team with expertise in structural biology, medicinal chemistry and bacteriology will establish a comprehensive knowledge base aimed at developing new antibiotics to treat MDR-Ng by targeting a bacterial protein virulence factor.
Development Of Small Molecule Modulators Of Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$621,558.00
Summary
Cancers rely on the deregulation of key cellular pathways. Along with biological and genetic tools, small molecules are powerful probes to understand these mechanisms. During the course of this research program, we will develop new and drug-like molecules that reinstate the cell death process to combat malignancies. This research will bring important advances for potential chemotherapies and create probes to better understand the biology of programmed cell death processes.
A Novel Metabolic Role For UDP Glycosyltransferase 8 (UGT8)
Funder
National Health and Medical Research Council
Funding Amount
$419,144.00
Summary
The UDP glycosyltransferases (UGTs) are a family of enzymes that remove drugs and toxins from the human body as well as control levels of naturally produced molecules such as bile acids and hormones. We found that a new member of this family called UGT8 processes bile acids in the kidney and intestine and can affect how bile acids act to regulate metabolism. Our studies uncover new roles for bile acids in liver, kidney and gut health and in metabolic disorders such as diabetes and obesity.
Glucocorticoid Resistance In Paediatric Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$394,721.00
Summary
Glucocorticoids are among the most effective drugs used in the treatment of many haematological malignancies, including leukaemia, lymphoma and multiple myeloma. However, the development of tumour cell resistance to these drugs remains a significant problem, and clinically relevant mechanisms of glucocorticoid resistance remain poorly understood. This project aims to define mechanisms of resistance to glucocorticoids and develop new drugs to reverse resistance.
Targeting Microtubules To Overcome Chemoresistance In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$594,336.00
Summary
Pancreatic cancer is a devastating disease with a dismal prognosis because it is extremely resistant to chemotherapy agents. We plan to examine the expression of proteins called microtubules in pancreatic cancer and assess their role in drug resistance. It is anticipated that the findings of these studies will lead to the development of effective approaches to sensitise the cancer cells to chemotherapy agents.
The WHO estimates there were ~189 million clinical cases & 584,000 malaria-related deaths in 2013. This translates to ~1,600 child deaths daily. There is no licensed malaria vaccine & all available drugs are associated with resistant parasites. This enormous health issue is driving the search for new therapies. We address this issue by identifying new drug candidates for malaria prevention, with unique modes of action to treatment drugs in order to overcome issues of parasite drug resistance.
Unraveling Fibrosis By Pharmacological Targeting Of The G Protein-coupled Receptor, RXFP1
Funder
National Health and Medical Research Council
Funding Amount
$798,618.00
Summary
Peptides, with their high specificity and low toxicity profiles, are highly attractive alternatives to small molecule drugs. H2 relaxin, a peptide hormone, has a strong potential for treating fibrosis. However, the large size of H2 relaxin makes it difficult and expensive to manufacture. Once administered to patients, it is also quickly degraded. We have developed a small anti-fibrotic relaxin peptide, and propose to understand its mechanism of action and improve its therapeutic indices.