Defining The Role Of A Palmitoylated Variant Of Sphingosine Kinase 1 In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$603,452.00
Summary
Sphingosine kinase is a protein that when dysregulated is involved in cancer development and progression. We have recently made a substantial breakthrough in this area by identifing a naturally occuring variant of sphingosine kinase that is constantly activated and has an enhanced ability to induce cancer. In this study we will examine and target this form of sphingosine kinase as a potential therapeutic intervention in cancer.
Disrupting Mucin-mucin Interactions To Treat Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$480,531.00
Summary
Diseases like asthma, emphysema and cystic fibrosis all feature the overproduction of mucus in the lungs that make it very difficult for patients to breathe and increases their susceptibility to infections. Few therapies are available for thinning this mucus, which is made thick by a network of linkages between proteins. We are studying these linkages and developing methods to break them up. This research could yield new mucus-thinning drugs to treat lung diseases.
The Proteomics Of The Von Hippel-Lindau (VHL) Tumour Suppressor Protein
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
This project primarily intends to identify novel modifications to the von Hippel-Lindau (VHL) protein which plays a role in tumour suppression and blood vessel growth. It is the purpose of this project to characterise these changes to VHL and ultimately, understand what these changes mean to the function of VHL protein, and modulate them to ameliorate VHL disease.
Understanding Age-related Protein Aggregation. The Mechanism Of Cataract And Its Prevention
Funder
National Health and Medical Research Council
Funding Amount
$709,333.00
Summary
Cataract arises from clouding of the eye lens due to the aggregation of crystallin proteins whose high concentration and close packing facilitate lens transparency. This proposal will investigate crystallin structure and interactions to understand the reasons for cataract formation and its prevention via the design of aggregation inhibitors. The results will facilitate the development of drugs to prevent cataract and other related protein aggregation diseases, e.g. Alzheimer’s and Parkinson’s.
Redefining The Pro-thrombotic Mechanism Of Von Willebrand Factor
Funder
National Health and Medical Research Council
Funding Amount
$750,005.00
Summary
Blood clotting is the underlying cause of heart attacks and strokes. The blood protein, von Willebrand factor, is a critical player in blood clotting and impairment of its function is life threatening. We have discovered that there are three forms of VWF in human blood that have different functions in blood clotting. Characterisation of these different forms will likely lead to new blood clotting diagnostics and improved therapies.
Defining The Machinery For Mitochondrial Turnover Governed By The Parkinson’s Disease Proteins PINK1 And Parkin
Funder
National Health and Medical Research Council
Funding Amount
$432,987.00
Summary
Parkinson’s disease is a degenerative disorder of the central nervous system in which the underlying cause is mostly unknown. To pave the way to a better understanding of what goes wrong, this study will investigate the function of PINK1 and Parkin, two proteins that are mutated in inherited forms of the disease that play important roles in maintaining cellular health. The results of this study will be used in exploring new therapeutic targets for the treatment of Parkinson’s disease symptoms.
Investigating The Substrate Specificity Of The Master Kinase LKB1 And The Pharmacological Targeting Of Its Substrate NUAK2 To Treat Cancers
Funder
National Health and Medical Research Council
Funding Amount
$384,768.00
Summary
Kinases are key regulators of cell signaling and emerging drug targets. LKB1 kinase specifically activates a set of substrates to modulate cellular processes, and its substrate NUAK2 is a novel target for cancer. I will elucidate the structural basis of how LKB1 recognizes its substrates and develop inhibitors targeting LKB1-NUAK2 interaction for cancer treatment. My project will provide key insights into kinase-dependent signaling and establish a new framework for therapeutics development.