Molecular Genetic Analysis Of BRCT Domain Function And RhoGEF Signalling In DNA-damage Response And Apoptosis.
Funder
National Health and Medical Research Council
Funding Amount
$195,691.00
Summary
Cancers arise as a consequence of a series of genetic changes, usually by mutation of DNA. DNA is consistently exposed to an array of damaging agents, but the majority of mutations are corrected by cellular repair mechanisms. We now know that if these mechanisms work normally, too few mutations persist for cancer to result. However if these DNA damage repair mechanisms are themselves faulty, a high mutation rate occurs and a high risk of cancer results. DNA damage has another outcome. If the dam ....Cancers arise as a consequence of a series of genetic changes, usually by mutation of DNA. DNA is consistently exposed to an array of damaging agents, but the majority of mutations are corrected by cellular repair mechanisms. We now know that if these mechanisms work normally, too few mutations persist for cancer to result. However if these DNA damage repair mechanisms are themselves faulty, a high mutation rate occurs and a high risk of cancer results. DNA damage has another outcome. If the damage is too extensive, the cell commits suicide, not because it cannot function, but because it senses the DNA damage and chooses to die. One poorly understood aspect of the response to DNA damage is how the cell senses the damage and activates the suicide process. We have discovered a novel gene that appears to play a role in this sensing and suicide signalling process. The mouse version of this gene can itself act as a cancer-causing gene. We propose, however, to study the equivalent gene in Drosophila melanogaster, a more powerful experimental system, to characterise in detail its role in these processes. In this way we hope to generate a much more detailed understanding of the way that cells deal with DNA damage and choose suicide when the damage is too severe.Read moreRead less
Functional Screening Of Novel Genes In Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Our faces are central to our ability to communicate, feed, breath and interact with each other. Birth defects that impact on the normal development of the face are common and affect not only the child but have a dramatic impact on the child's family as well. The genetic causes of most facial birth defects are unknown. This project will develop a method for determining how development of the face is controlled and will help identify genes that are responsible for facial birth defects.
Implications Of Bacterial Load For Vaccine Efficacy And Antibiotic Treatment Outcomes In High-risk Populations
Funder
National Health and Medical Research Council
Funding Amount
$345,000.00
Summary
Otitis media (middle ear disease) is a common childhood infection, and a major concern in remote Aboriginal communities of the Northern Territory. For these children, otitis media commences within the first few weeks of life and progresses to perforation of the ear drum in 60% of children by 12 months of age. Few children in remote Aboriginal communities have normal ear status or normal hearing and many have conductive hearing loss, affecting language development and education. Otitis media in t ....Otitis media (middle ear disease) is a common childhood infection, and a major concern in remote Aboriginal communities of the Northern Territory. For these children, otitis media commences within the first few weeks of life and progresses to perforation of the ear drum in 60% of children by 12 months of age. Few children in remote Aboriginal communities have normal ear status or normal hearing and many have conductive hearing loss, affecting language development and education. Otitis media in these children results from infection with the bacteria Streptococcus pneumoniae, Haemophilus influenzae and-or Moraxella catarrhalis. Therefore the types of interventions we are using to combat the high prevalence of ear disease are antibiotic therapy, Streptococcus pneumoniae vaccination, and hygiene interventions. However we fear that the high load of bacteria carried by these children compromises the treatment and prevention strategies. The current proposal will test this hypothesis, and if found to be true, there will be implications for the management of otitis media. For example, dose, frequency and choice of antibiotic treatment, and vaccine schedule changes including an early dose or a booster dose.Read moreRead less
Azithromycin Versus Placebo In The Treatment Of Asymptomatic Acute Otitis Media In Young Aboriginal Children : A RCT
Funder
National Health and Medical Research Council
Funding Amount
$1,357,460.00
Summary
Remote Aboriginal children have the highest rates of severe ear infection reported in the medical literature. At any time, large numbers of children have a bulging eardrum (acute otitis media) but most are completely asymptomatic. In our previous antibiotic study, acute otitis media (AOM) persisted in 50% of children after 1 week of treatment. In terms of clinical success, it didn't make any difference whether azithromycin or amoxicillin was used (although azithromycin seemed to be better at red ....Remote Aboriginal children have the highest rates of severe ear infection reported in the medical literature. At any time, large numbers of children have a bulging eardrum (acute otitis media) but most are completely asymptomatic. In our previous antibiotic study, acute otitis media (AOM) persisted in 50% of children after 1 week of treatment. In terms of clinical success, it didn't make any difference whether azithromycin or amoxicillin was used (although azithromycin seemed to be better at reducing the level of infection). Currently local clinicians are: i) uncertain whether antibiotics make any difference at all; and ii) reluctant to devote resources to case-finding without good evidence of substantial benefit. In this randomised controlled trial, we will determine the benefits of 2 doses of azithromycin given 1 week apart in children with asymptomatic acute otitis media will improve health outcomes. The results of the trial will become the best available evidence to guide the medical management of asymptomatic AOM in high-risk children. We anticipate that it will make an important contribution in the shift toward more effective prevention and management of otitis media in Australian Aboriginal children. It will also have implications for all disadvantaged populations where adverse outcomes are common and compliance with recommended treatment is poor.Read moreRead less