Population Prevalence And Environmental-genetic Predictors Of Food Allergy In An Infant Cohort
Funder
National Health and Medical Research Council
Funding Amount
$551,642.00
Summary
This study will measure which children are at greatest risk of food allergy. We plan to recruit 5000 children to test for food allergies, as well as asking a range of questions on different lifestyle factors such as diet and history of allergies . If positive, participants will be invited to a hospital clinic for tests and treatment. This will allow us to describe the epidemiology of food allergy, and assist the development of better services for those with food allergy in the community.
Improved Support For Regional And Remote Paediatric Oncology Families: A Randomised Controlled Trial Of Videotelephony
Funder
National Health and Medical Research Council
Funding Amount
$304,843.00
Summary
Childhood cancer presents a major life stressor for the entire family. Significant changes to the everyday lives of families, practically, socially and emotionally cause major disruption. There is evidence that this disruption results in isolation and poor communication between family members, anxiety, low self-esteem and school problems for siblings and anxiety, post-traumatic stress symptoms and risk of depression for parents. Providing ongoing support to these families is an essential part of ....Childhood cancer presents a major life stressor for the entire family. Significant changes to the everyday lives of families, practically, socially and emotionally cause major disruption. There is evidence that this disruption results in isolation and poor communication between family members, anxiety, low self-esteem and school problems for siblings and anxiety, post-traumatic stress symptoms and risk of depression for parents. Providing ongoing support to these families is an essential part of care. The Royal Children's Hospital (RCH) Paediatric Oncology Service in Brisbane is the major tertiary paediatric referral centre for Queensland, northern New South Wales and the southwest Pacific. A multidisciplinary team of medical, nursing, and allied health professionals provides care and support to children with cancer, as well as their families. Each year around 100 newly diagnosed patients are cared for. Around 60% of the families cared for by the service live in regional and remote areas. There are a number of challenges which inhibit the equitable provision of specialist health services to these areas including availability of health care professionals and accessibility due to distance, time, cost and transport. For paediatric oncology families, opportunities to receive support are limited. One possible solution is the use of online support mechanisms, such as videotelephony, to facilitate the provision of much needed support to patients, parents, siblings and the family as a whole. The objective of this research is to see if videotelephony can be used to support regional and remote families of the Royal Children's Hospital Paediatric Oncology Service providing indizidualised communication, education, counselling and monitoring. This will present a new and innovative use of videophone technology as well as a new method for supporting regional and remote oncology patients and their families.Read moreRead less
Cognitive Impairments And Post Traumatic Stress Symptoms In Children With Traumatic Brain Injury: A Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$482,250.00
Summary
Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and Victoria alone. Many children who experience a brain injury go on to have long-term difficulties such as significant educational and social problems. Post-traumatic stress occurs in children following traumatic physical injury. However it is not clear to what extent this is so for children who have received a traumatic brain injury. Furthermore, when there is a traumatic brain injury and traumatic ....Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and Victoria alone. Many children who experience a brain injury go on to have long-term difficulties such as significant educational and social problems. Post-traumatic stress occurs in children following traumatic physical injury. However it is not clear to what extent this is so for children who have received a traumatic brain injury. Furthermore, when there is a traumatic brain injury and traumatic stress, it is not clear how these interact, how they influence long-term outcomes, and what factors such as pre-injury functioning and family support and distress mediate outcomes. These issues are very important since effective rehabilitation of children following traumatic brain injury is essential to maximise long-term functioning and minimise disability. To be effective, rehabilitation must be guided by the knowledge about key factors that determine the recovery process. This study aims to provide answers to these questions by following two cohorts of children (aged 6-14) over 18 months after receiving a traumatic brain injury. In total 240 children will be recruited from Brisbane and Melbourne hospitals. They will be assessed at three, six, twelve and eighteen months post-injury using measures of cognitive, psychological and social functioning. Information on parent distress and behaviours will also be obtained. The information obtained will provide the basis for the development of a specific rehabilitation strategy for children with traumatic brain injury, including information on strategies to help prevent any confounding impact of post-traumatic stress on recovery.Read moreRead less
Non-viral Vectors For Targeted Delivery Of RNAi Nucleotides To Cervical Cancers
Funder
National Health and Medical Research Council
Funding Amount
$415,738.00
Summary
RNA interference (or gene silencing) is a new technique whereby we are able to turn off the expression of a particular gene either temporarily or permanently. Cancer is basically a genetic disease where certain protective genes are lost or cancer-causing genes expressed. Gene silencing holds great promise in the treatment of genetic disorders, infectious diseases and cancer. Cervical cancer is caused by infection with the human papillomavirus and the expression of two cancer-causing genes. Using ....RNA interference (or gene silencing) is a new technique whereby we are able to turn off the expression of a particular gene either temporarily or permanently. Cancer is basically a genetic disease where certain protective genes are lost or cancer-causing genes expressed. Gene silencing holds great promise in the treatment of genetic disorders, infectious diseases and cancer. Cervical cancer is caused by infection with the human papillomavirus and the expression of two cancer-causing genes. Using RNA interference we can turn off the expression of these two genes which results in the death of the cancer cell. We are also able to cure mice of tumours derived from human cervical cancer. The major issue with gene silencing is how to deliver it effectively to patients. Here we are investigating novel nanoparticulate systems to deliver this new gene-inhibiting drugs preferentially to the tumour site.Read moreRead less
Polarized Trafficking Of E-cadherin In Epithelial Cells.
Funder
National Health and Medical Research Council
Funding Amount
$515,564.00
Summary
The cell adhesion protein E-cadherin is expressed in all epithelial tissues of the body where it has essential functions during development and in the adult in establishing and maintaining polarized cell monolayers. E-cadherin is also a vital tumour suppressor, its normal function guarantees that cells or even early tumours cannot metastasise; in contrast E-cadherin is always lost or malfunctions in malignant tumours. Earlier studies showed that E-cadherin is constantly moved, or trafficked, to ....The cell adhesion protein E-cadherin is expressed in all epithelial tissues of the body where it has essential functions during development and in the adult in establishing and maintaining polarized cell monolayers. E-cadherin is also a vital tumour suppressor, its normal function guarantees that cells or even early tumours cannot metastasise; in contrast E-cadherin is always lost or malfunctions in malignant tumours. Earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. This trafficking has dual roles, firstly in delivering newly-made E-cadherin to the surface where it functions and secondly, in regulating its adhesive function. Our research in this project is focussed on the molecules and intracellular compartments that control the delivery of E-cadherin to the cell surface. E-cadherin must be sorted in order to be delivered to the correct side of the cell. Having previously discovered the sorting signal in E-cadherin, we will now identify the cognate adaptor protein(s) that accomplish this sorting. New imaging techniques allow us to study protein trafficking inside live cells. Such studies have recently revealed that E-cadherin passes through a recycling endosome compartment on its way to the cell surface. This unexpected route, and the structure and role of the recycling endosome will now be studied in detail in live cells. Finally we will compare the sorting and trafficking of E-cadherin with the closely-related N-cadherin protein, to determine whether there are inherent differences in their trafficking that could explain their opposite roles in tumour cells, where N-cadherin is substituted for E-cadherin and allows metastatic behaviour. These studies will provide important information for understanding the adhesive and tumour suppressive roles of E-cadherin. In addition our findings will generate information fundamental to our understanding of cell polarity and protein sorting.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
Identifying Long-range Regulatory Elements Of The Breast Cancer Susceptibility Gene, BRCA1
Funder
National Health and Medical Research Council
Funding Amount
$612,842.00
Summary
BRCA1 is a breast cancer susceptibility gene implicated in both familial and sporadic breast cancers. The mechanisms controlling BRCA1 expression are poorly understood. We will identify DNA sequences critical for regulation of the BRCA1 gene. We hypothesise that these regions are mutational hot spots conferring an increased breast cancer risk. A better understanding of the pathways responsible for promoting BRCA1-associated breast cancer will provide important diagnostic and treatment targets.
Pharmacology Of Potential Anti-Tumour Agents: Iron Chelators Of The BpT Class
Funder
National Health and Medical Research Council
Funding Amount
$585,455.00
Summary
Pharmacology of Potential Anti-Tumour Agents: Iron Chelators of the BpT Class Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Renewal, we will perform pharmacological and preclinical studies to promote the development of BpT chelators as novel anti-tumour agents.
E-Cadherin Endocytosis In Morphogenesis: Recycling And Growth Factor Induced Uptake.
Funder
National Health and Medical Research Council
Funding Amount
$498,088.00
Summary
E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell ....E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell surface E-cadherin serves to regulate its role in adhesion. More recently, we and others have shown that E-cadherin is endocytosed in response to growth factors, in conjunction with the activated growth factor receptors themselves. E-cadherin can influence the trafficking and signaling of these receptor tyrosine kinases. This joint endocytosis is an elegant mechanism for the simultaneous downregulation of cell adhesion and activation of signaling for cell growth and motility. The growth and differentiation of epithelial cells during tissue patterning or morphogenesis relies critically on these endocytic pathways. Our research is aimed at defining the endosomes and cellular machinery involved in E-cadherin-receptor endocytosis, moreover we will pursue initial findings suggesting that there are different pathways and fates for E-cadherin endocytosed at the behest of different growth factors. We will study endocytosis during the processes of epithelial cyst formation and tubulation of cysts as an in vitro model for mammalian morphogenesis. These studies will provide important and novel information for understanding the roles of E-cadherin in adhesion and in growth factor signaling during epithelial morphogenesis. Ultimately these findings will be of relevance to epithelial development and the prevention of cancer.Read moreRead less
The Functional Roles Of ADAMs In The Regulation Of Embryo Implantation.
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
The initiation of pregnancy in humans and rodents hinges upon the ability of the embryo to attach to the wall of the uterus and invade into the uterine tissue. This process of embryo implantation is tightly regulated and depends on the secretion of enzymes and regulators of these enzymes. A newly identified family of enzymes which might be important in this process is the ADAMs family. These enzymes have the potential to facilitate both cell attachment and cell invasion and also to activate othe ....The initiation of pregnancy in humans and rodents hinges upon the ability of the embryo to attach to the wall of the uterus and invade into the uterine tissue. This process of embryo implantation is tightly regulated and depends on the secretion of enzymes and regulators of these enzymes. A newly identified family of enzymes which might be important in this process is the ADAMs family. These enzymes have the potential to facilitate both cell attachment and cell invasion and also to activate other enzymes and growth factors. Recent studies in our laboratory have shown the ADAMs to be expressed both at the most invasive time of implantation and when invasion is being down-regulated. This project will examine the role of the ADAMs in embryo implantation facilitating attachment and invasion into the uterus by acting enzymatically on the uterine tissue and by activating other enzymes. It will also determine the role of ADAMs in down-regulating invasion potentially by activating a growth factor, TNF-alpha. Knowledge of this process and particularly its regulation is important for the treatment of pregnancy associated diseases that arise from improper implantation. These include infertility, placenta accreta, choriocarcinoma, miscarriage and pre-eclampsia. Furthermore, an understanding of the regulation of implantation will contribute to the treatment of other conditions associated with cell invasion such as cancer metastasis.Read moreRead less