Enabling Personalised Risk Assessment For Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Bowel cancer screening will be most effective in disease prevention if it is applied proportionately to individual person's risk. Risk-based screening requires a risk calculator to assess personal risk. By utilising existing large, international datasets, I will identify the risk factors specific for different bowel cancer types and incorporate them to upgrade the prediction model that I have developed. This will achieve more accurate risk prediction to enable personalised risk-based screening.
The Role And Inheritance Of Constitutional Epimutations In Early-onset Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$347,551.00
Summary
Traditionally familial cancers are thought to be caused by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that chemical attachments to one gene (MLH1) stops it working, even where there is no spelling mistake, and that those chemical changes can be inherited in families with bowel cancer. We will determine how frequently this type of defect occurs in bowel cancer patients, how and why it arises, and if other cancer genes are similarly affected.
Epimutations As Germ-line Defects In Hereditary Cancer Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$385,925.00
Summary
Traditionally familial cancers were thought to be caused and inherited by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that a 'chemical coat' around the MLH1 gene, causing it to be switched off, can also be inherited in some cases of bowel cancer, without any mistakes within the gene's code. We will determine if this 'coat' causes other types of cancer and if this runs in families. We also hope to find out how the coat is formed and may be reversed.
Hyper-sensitivity Of The Circadian System To Light In Delayed Sleep Phase Disorder
Funder
National Health and Medical Research Council
Funding Amount
$378,858.00
Summary
Delayed Sleep Phase Disorder (DSPD) is a circadian rhythm sleep disorder characterized by a difficulty in initiating sleep at night and difficulty in waking at times required for work or school. It is associated with excessive daytime sleepiness, reduced academic and work performance, increased anxiety and depression and reduced quality of life. This study examines increased sensitivity of the brain's 24-hour biological clock to light as a cause of the abnormal timing of sleep in DSPD.
Endocrine Therapy Tolerance As A Cancer Cell Survival Mechanism For Late Recurring Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$450,083.00
Summary
~25% of breast cancer deaths are attributable to cancers that have failed endocrine therapy and recur >5 years after primary diagnosis. These cancers are not well understood because their long latency makes them difficult to study. We have new models of this disease that identify a “therapy tolerant” population, and this is likely to re-emerge to cause late recurrence. Our work could potentially identify new biological tests and therapeutic strategies to treat late recurring breast cancer.
Phase Shifting Endocrine And Sleep/activity Rhythms With Light And Serotonergic Drugs
Funder
National Health and Medical Research Council
Funding Amount
$561,430.00
Summary
All biological systems, including those of humans, are influenced by changes in the environment, especially by variations in the amount of daylight. In animals the external rhythm of light and darkness interacts with a small part of the brain called the suprachiasmatic nucleus (SCN-often called the biological clock) which has its own self sustained rhythms. The SCN in turn orchestrates rhythms in the secretion of the hormone melatonin from the pineal gland, body temperature, the timing of sleep ....All biological systems, including those of humans, are influenced by changes in the environment, especially by variations in the amount of daylight. In animals the external rhythm of light and darkness interacts with a small part of the brain called the suprachiasmatic nucleus (SCN-often called the biological clock) which has its own self sustained rhythms. The SCN in turn orchestrates rhythms in the secretion of the hormone melatonin from the pineal gland, body temperature, the timing of sleep and the secretion of other hormones. The aim of this study is to extend our knowledge of the inter-relationships between light, the chemical messengers that nerves use to communicate with each other, the biological clock and rhythms in body functions. We will concentrate on one particular chemical messenger called serotonin which we believe plays an important role in keeping rhythms in synchrony with the natural day-night cycle. The results are expected to be of benefit in understanding how certain sleep timing disorders arise and provide some insight into how they might be treated.Read moreRead less
Upper Airway Dilator Muscle Activity During Sleep Onset.
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Disorders of breathing during sleep are recognised as a major health problem. Of these, Obstructive Sleep Apnoea is the most prevalent, occurring in approximately 4% of the male and 2% of the female population. In this disorder the upper airway collapses during sleep causing cessation of airflow and subsequent oxygen desaturation. The airway is thought to occlude because dilator muscles are unable to sustain patency in the face of the negative pressures generated by inspiratory effort. In order ....Disorders of breathing during sleep are recognised as a major health problem. Of these, Obstructive Sleep Apnoea is the most prevalent, occurring in approximately 4% of the male and 2% of the female population. In this disorder the upper airway collapses during sleep causing cessation of airflow and subsequent oxygen desaturation. The airway is thought to occlude because dilator muscles are unable to sustain patency in the face of the negative pressures generated by inspiratory effort. In order for patency of the airway to be re-established some form of arousal from sleep must occur . As the UA is likely to collapse on the resumption of sleep, the cycle becomes repetitive, causing significant sleep disruption. OSA is a significant health risk, being associated with increased risk of cardiovascular disorders, increased mortality, excessive daytime sleepiness, reduced daytime performance and increased risk of accidents. In previous work we have demonstrated that normal sleep related changes in the activity of upper airway dilator muscles result in a reduction in the calibre of the airway at sleep onset. This exposes some individuals, such as those with narrow airways, to airway obstruction during sleep. We have also reported that elderly men have larger reductions in upper airway muscle activity at sleep onset than younger men, suggesting one reason why they may have a higher prevalence for Obstructive Sleep Apnea. The aim of the present project is to determine what causes the larger reductions in upper airway muscle activity in older males. The answer to this question will contribute to understanding why this group is so susceptible to Obstructive Sleep Apnea and will elucidate the mechanisms leading to the disorder.Read moreRead less