Directed Molecular Evolution Of G Protein-coupled Receptors For Stable And Functional Expression In Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$383,479.00
Summary
Approximately half of all prescription drugs on the market act on G protein coupled receptors (GPCRs). The mechanisms underlying GPCR function are mainly unknown due to a lack of structural information. No solved structures exist for any of the estimated 800 human GPCRs, making it difficult to design new drugs. By applying advanced protein engineering techniques I aim to produce human GPCRs in bacteria to ultimately acquire structural information, which will enable novel drug development.
Structural And Drug Discovery Studies Of Medically Important Protein Complexes
Funder
National Health and Medical Research Council
Funding Amount
$438,577.00
Summary
My research is focused on structural studies of medically important biological systems, where specific protein complex formation contributes to human illnesses. I use X-ray crystallography to visualize the whole complex at atomic resolution as well as to determine whether binding partners have undergone changes in shape upon complex formation. This structural information then helps me in drug design with goals to either disrupt or modulate the complex.
Mechanism Of Interaction Of VWC Domains And Consequence For Protein Function
Funder
National Health and Medical Research Council
Funding Amount
$516,803.00
Summary
More than 1000 proteins contain a type of module known as the VWC domain. These domains are discreet sections of the protein that are very important for how the protein works. Proteins containing this domain are involved in normal functioning of the human body and in diseases of the nervous system and blood, among others. The main function of the VWC domain is to link proteins together in complexes. How this is achieved is not known and is what we aim to discover.
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.
Structure-function Inter-relationships Of Small Heat-shock Chaperone Proteins
Funder
National Health and Medical Research Council
Funding Amount
$240,990.00
Summary
In vivo, most proteins only function over a narrow temperature or pH range. For example, if the solution containing a particular protein is heated (stressed), the protein will unfold, aggregate and potentially precipitate. The act of protein precipitation is an irreversible process that, in many cases, has deleterious consequences for cell viability. Protein precipitation is associated with a diversity of diseases, e.g. cataract and neurodegenerative diseases such as Alzheimer's, Creutzfeldt-Jak ....In vivo, most proteins only function over a narrow temperature or pH range. For example, if the solution containing a particular protein is heated (stressed), the protein will unfold, aggregate and potentially precipitate. The act of protein precipitation is an irreversible process that, in many cases, has deleterious consequences for cell viability. Protein precipitation is associated with a diversity of diseases, e.g. cataract and neurodegenerative diseases such as Alzheimer's, Creutzfeldt-Jakob and Parkinson's diseases. Nature has evolved cellular mechanisms to minimise protein misfolding, aggregation and precipitation which principally utilise a diverse group of controlling or regulatory proteins called molecular chaperones. Amongst the most important of these are the small heat-shock proteins (sHsps) which are found in all organisms. sHsps function by interacting in a very efficient manner with destabilised proteins to prevent their precipitation. Little is known, however, about the structure of sHsps nor the mechanism by which they perform their chaperone action. This proposal will address these fundamental aspects via the use of a variety of spectroscopic techniques, principally nuclear magnetic resonance (NMR) spectroscopy.Read moreRead less
I am a structural biologist with a background in pharmacy. My research focuses on dissecting the molecular mechanisms of disease-causing proteins to underpin the development of new and improved therapeutics
Protein Networks Mediating Copper Balance And Their Break-down In Disease.
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Neurological disorders (eg. Alzheimer s, Parkinson s and prion diseases) impose a growing health burden on society. Exciting new therapeutic possibilities stem from the discovery that copper (Cu) plays a central role in the disease process. Our research will help foster a holistic understanding of the protein network regulating copper balance, particularly in the brain, and where it breaks down in disease. Clinical benefits include new targets for diagnosis and treatment of Cu-related diseases.
The Role Of Alpha-haemoglobin Stabilising Protein In Haemoglobin Production And As A Therapeutic For Thalassaemia.
Funder
National Health and Medical Research Council
Funding Amount
$320,936.00
Summary
Thalassaemias are the most common hereditary diseases effecting the production of red blood cells. The underlying cause of disease is a failure to produce normal quantities of haemoglobin (Hb; the essential oxygen-carrying molecule in blood), resulting in severe anaemia. We have discovered a new protein with an important role in Hb production. We will elucidate the function of this protein in red blood cells and investigate novel treatments for thalssaemia disease.