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.
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.
HtrA4-induced Endothelial Dysfunction In Early-onset Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$86,073.00
Summary
Preeclampsia (PE), a life-threatening disorder of pregnancy, is characterized by a sudden increase in blood pressure in association with wide-spread endothelial dysfunction. Placenta-derived factors are believed to cause PE development. Our recent studies have identified that HtrA4, a placenta-specific serine protease may contribute to endothelial dysfunction. This study will investigate the mechanisms of HtrA4-induced endothelial dysfunction.
Structural Investigation Into The Regulation Of The Colony Stimulating Factor Receptor, C-FMS.
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
The colony stimulating factor receptor, c-FMS is a member of a family of protein signalling molecules expressed on the cell surface that are implicated in the development of serious diseases in humans, such as inflammatory diseases and cancer. A number of important proteins bind to and regulate c-FMS in different ways. I intend to visualise these interactions to further understand how c-FMS activity is controlled by alternative means.
Investigation Of Neuregulin Precessing By Beta-site APP Cleaving Enzyme And Gamma Secretase In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$46,715.00
Summary
Schizophrenia (SCZ) is a complex psychiatric disorder that appears in male and female around adulthood. To date there is no clear pathological symptoms to identify SCZ individuals and place them in a specific group. Some proteins are genetically associated with this disease. I will investigate how some of these proteins disturb the function of the brain in human. My recent published data shows decrease of one of the proteins in the brain of SCZ group. My project may help develop novel and more s ....Schizophrenia (SCZ) is a complex psychiatric disorder that appears in male and female around adulthood. To date there is no clear pathological symptoms to identify SCZ individuals and place them in a specific group. Some proteins are genetically associated with this disease. I will investigate how some of these proteins disturb the function of the brain in human. My recent published data shows decrease of one of the proteins in the brain of SCZ group. My project may help develop novel and more selective therapies with less side-effects.Read moreRead less
Role Of FHA Domains As Protein-protein Interaction Modules In Cell Signalling
Funder
National Health and Medical Research Council
Funding Amount
$191,973.00
Summary
The proper processing of information in cells involves the association of different proteins to signalling complexes. We will decipher the role the so-called FHA module plays in the formation of protein complexes. FHA modules are present in several proteins that are important for the repair of damaged DNA and the stability of chromosomes. Understanding the structure and function of this module will be relevant for various forms of cancer where DNA is damaged.
LMO2-containing Complexes In Leukemia And Blood Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$803,652.00
Summary
Childhood T-cell leukemias have a poor prognosis for recovery. We are determining, with atomic level precision, how the proteins Lmo2 (also linked to prostate and other cancers) and Tal1, and their binding partners contribute to both normal blood cell development and T-cell leukemia. With this information we are developing reagents that can be used to disrupt disease-causing complexes, and which will lead towards the development of new, specific, therapeutics for leukemias and other cancers.