Inherited Genetic Variants As Prognostic Markers For Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$623,972.00
Summary
Bowel cancer is a major health burden. Surgical resection of the primary cancer is often possible at diagnosis, yet in many patients the cancer will recur. Together with mutations, inherited genetic variants influence the rate of bowel cancer growth. This study aims to identify inherited variants predictive of cancer recurrence. Improved prediction of recurrence will permit more targeted use of clinical interventions, tailored to the individual patient, ultimately improving patient survival.
Molecular Mechanism And Therapeutic Implications Of Prion Disease Strain Types In Sporadic Creutzfeldt Jakob Disease.
Funder
National Health and Medical Research Council
Funding Amount
$345,634.00
Summary
The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms also exist. Prion diseases are transmissible by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been conclusively identified. However, a major component of purified prions is an ....The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms also exist. Prion diseases are transmissible by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been conclusively identified. However, a major component of purified prions is an abnormal disease associated form of the host prion protein. Differences in the duration of illness and pathology of sporadic CJD suggests that the disease may be caused by different prion strains. The existence of different prion strains may explain the limited clinical success of anti-prion therapeutics modeled in rodent models of prion diseases. In this study a cell-free model of prion propagation will be used to investigate the basis of human prion strains. This assay will also be used to identify and determine whether the therapeutic efficacy of anti-prion compounds is influenced by human prion strain type. This study will represent the first host species and prion strain specific screen of anti-prion therapeutics aimed at developing the best possible model for the identification and development of therapeutics for human prion diseases.Read moreRead less
Human Arylamine N-acetyltransferase Regulation And Function - Effect Of Genetic Poymorphisms.
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
How we handle chemicals that enter our bodies depends on a series of enzymes that are responsible for breaking down the chemicals and eliminating them. The activity of many of these enzymes varies between individuals so our responses to chemicals and drugs is different for each individual. Some of the enzymes vary because of inherited mutations, but others vary because of the diets we eat and the environment in which we live. This project will investigate a major enzyme called acetlytransferase ....How we handle chemicals that enter our bodies depends on a series of enzymes that are responsible for breaking down the chemicals and eliminating them. The activity of many of these enzymes varies between individuals so our responses to chemicals and drugs is different for each individual. Some of the enzymes vary because of inherited mutations, but others vary because of the diets we eat and the environment in which we live. This project will investigate a major enzyme called acetlytransferase that has been implicated as a risk factor in diseases such as cancer, asthma, liver cirrhossis and adverse drug reactions. We plan to look at the enzyme in cells and determine what environmental factors contribute to its variation between individuals, and how this impacts on the genetic mutations that have been found in its gene. From these studies, we will have a much better undersanding of how different people metabolise foreign chemicals, and should be able to predict those most at risk of certain diseases.Read moreRead less
The Molecular Basis For The Increased Incidence Of Thrombosis Associated With The Prothrombin G20210A Gene Polymorphism
Funder
National Health and Medical Research Council
Funding Amount
$213,838.00
Summary
Prothrombin is an important enzyme involved in the formation of blood clots. Recently, a mutation was discovered in the prothrombin gene. This mutation occurs at a frequency of 2% in the normal population but occurs at an increased frequency (6%) in patients with thrombosis and is associated with an increase in the levels of prothombin in the blood. The position of this mutation in the prothrombin gene corresponds to the last residue of the prothrombin mRNA. We have preliminary data to suggest t ....Prothrombin is an important enzyme involved in the formation of blood clots. Recently, a mutation was discovered in the prothrombin gene. This mutation occurs at a frequency of 2% in the normal population but occurs at an increased frequency (6%) in patients with thrombosis and is associated with an increase in the levels of prothombin in the blood. The position of this mutation in the prothrombin gene corresponds to the last residue of the prothrombin mRNA. We have preliminary data to suggest that this mutation results in the prothrombin mRNA being more stable, which in turn allows for the production of more prothrombin protein, leading to an increased risk of developing a blood clot. The aim of this project is to explore the mechanisms leading to the elevated levels of prothrombin observed patients with this mutation.Read moreRead less
Understanding The Pharmacoregulation Of The Extracellular Calcium Sensing Receptor.
Funder
National Health and Medical Research Council
Funding Amount
$744,943.00
Summary
Calcium sensing receptors (CaSR) are important regulators of hormone release and modulators of kidney transport, digestion-absorption-satiety and bone mass. In each case, CaSRs adopt a characteristically distinct activating mechanism that we will unravel in detail sufficient for the development of novel chemotherapies e.g., for osteoporosis and obesity. We also anticipate early application of CaSR-based therapies to clinically significant genetic disorders e.g., neonatal hyperparathyroidism.
Structural Basis For Inhibition Of Malaria Invasion By Targeting The Apical Membrane Antigen Of Plasmodium Falciparum.
Funder
National Health and Medical Research Council
Funding Amount
$434,134.00
Summary
3 million children die every year from malaria infections. A leading vaccine candidate is a protein from the malaria parasite called AMA1. Humans that have been infected with malaria make antibodies to this protein which can kill parasites, however little is known about how this occurs. We aim to identify regions of the protein that generate antibodies that prevent malaria parasites from invading human cells and help in the search for a vaccine against malaria.