The importance of research at the Drug Discovery Biology theme is reflected in our emphasis on five key therapeutic foci: neurological disease, metabolic disease, cardiovascular disease, pain and inflammation and cancer.
Neurological disease View
Mental illness represents the leading cause of disability burden in Australia. Given an ageing population and the ongoing demands of the modern lifestyle, the incidence of neurodegenerative and neuropsychiatric disease is on the rise.
Unfortunately, the attrition rate associated with novel drug discovery for central nervous system (CNS) disorders is unacceptably high. This reflects the difficulty in understanding and treating neurodegenerative and neuropsychiatric diseases, including schizophrenia, anxiety and depression, which are complex and polygenic in nature.
Studies at the Drug Discovery Biology theme focus on understanding how modulation of G protein-coupled receptor targets in the CNS can provide new insights into mechanisms underlying neurological disease — in particular deficits associated with schizophrenia — and identify novel therapeutic modalities.
Metabolic disease View
Obesity has reached epidemic proportions and is associated with widespread health problems.
Chronic high-caloric intake and lack of exercise result in the storage of excess energy as lipid in body fat depots. The increases in body fat then trigger metabolic and inflammatory responses that lead to insulin resistance, type 2 diabetes, cardiovascular disease and increased risk of cancer.
Although changes in lifestyle are a first-line treatment option, most patients require additional therapeutic intervention.
The Drug Discovery Biology theme studies target G protein-coupled receptors as well as cytokine receptors, and focus on three main avenues for therapy of obesity and diabetes:
- to modulate adipocyte metabolism
- to activate glucose disposal in skeletal muscle
- to enhance and preserve the release of insulin from pancreatic islets
- to mitigate the harmful effects of diabetes on the cardiovascular system
Cardiovascular disease View
Coronary heart disease kills more Australians than any other single disease. It shows a strong association with Type II diabetes, which has emerged as a global public health crisis. Many people survive a heart attack (myocardial infarction) only to live shorter lives of reduced quality because of damage to the heart that occurred during the infarction. Heart failure, in which the damaged heart cannot eject sufficient blood, or sudden death due to electrical dysfunction in scarred regions of the heart, are common problems after myocardial infarction.
Our work at the Drug Discovery Biology theme focuses on developing new treatments for heart failure resulting from interruptions in coronary blood supply (such as in heart attack) or as a result of diabetes. We are currently identifying and developing G protein-coupled receptor ligands that show desired disease-specific signalling with reduced side effects.
Pain and inflammation View
Inflammation and pain are conserved protective mechanisms that are essential for survival. Inflammation, characterised by acute changes in the circulatory and immune systems, protects against infection. Pain allows avoidance of damaging stimuli.
Dysregulated chronic inflammation underlies diseases of global relevance — such as cardiovascular disease, cancer, diabetes, obesity and autoimmune diseases — and can cause chronic pain. Chronic inflammation and pain are major causes of human suffering, yet are poorly understood.
Research at the Drug Discovery Biology theme seeks to understand the basic mechanisms that control signalling of inflammation and pain, and determine whether defects in these regulatory mechanisms cause disease.
One in two Australians will be diagnosed with cancer during their lifetime. Most anti-cancer drugs are cytotoxic with significant side effects, so new highly selective drugs with minimal toxicity are critically needed.
Studies at the Drug Discovery Biology theme investigate the tumour microenvironment as a novel therapeutic target. We study the peripheral nervous system and its capacity to regulate key tumour processes, including metastasis, inflammation, angiogenesis and hypoxia. We are also examining the cascade of fatty liver disease, inflammation and fibrosis in the progression to liver cancer.
We are evaluating drugs that interact with the peripheral nervous system as novel strategies to limit cancer progression, and working with medicinal chemists to design and evaluate new anti-cancer compounds.