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 Basis For Targeting Wnt Signalling Pathway In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Cells sense and respond to a variety of stimuli by activating different signaling pathways. The Wnt pathway is important in embryonic development as it controls cell division and specialization. In adults, dysregulation of this pathway can lead to aberrant cell division and cancer. This proposal will use structural biology to look at several steps of this pathway at the molecular level. This will provide answers on how this pathway works and will lead to new ways to target it therapeutically.
Developing Novel Peptide-based Therapeutics And Technologies To Mitigate Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,161,383.00
Summary
Fibrosis (tissue scarring) is an unmet medical problem that adversely affects both human health and medical devices. It causes organ (e.g. heart, kidney) failure leading to death. Fibrotic encapsulation causes medical device (e.g. surgical mesh) failure. Our team has discovered a peptide, B7-33, that mitigates fibrosis in the short-term. Our IDEAS grant aims to develop long-acting B7-33 therapies and, to employ long-acting B7-33 mimetics in anti-fibrotic compositions for surgical meshes.
The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein coupled r ....The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein coupled receptors, the transmission of the message to the interior of the cell involves yet another protein called G protein. It is extremely important to unravel how each of these components, the stimulating agent, the receptor and G protein, works in order to understand how the cells respond to various chemical signals. To make this process even more complex, it was recently shown that another newly discovered group of proteins called receptor activity modifying proteins (RAMPs) too play a critical role in some systems. Understanding what actually is the role of these new players, and how they team-up with the other components to elicit a specific response to a chemical stimulus, forms the basis of this proposal. Such knowledge is central to the unraveling of the processes involved in the maintenance of health, abnormalities that lead to disease, and in the development of new treatments.Read moreRead less