Exploration Of The Role Of Microbes In Gastrointestinal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$687,974.00
Summary
This fellowship will investigate diseases of the gastrointestinal tract of children. The research program will undertake a range of is a highly innovative projects including; development of an effective rotavirus vaccine to be administered to newborns; genetic characterisation of rotavirus strains able to escape vaccine protection; and how alterations in the human gut microbiome (bacteria and viruses) influence the development/relapse of CrohnÍs disease.
Analysis Of The Role Of Rotavirus Infection In Development Of Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$348,875.00
Summary
Our earlier studies in children with a family history of type 1 diabetes have shown that infection with a common virus, rotavirus, may be one factor contributing to their progression to diabetes. Rotavirus is the most common cause of diarrhoea, vomiting and dehydration in young children, and it was thought that rotavirus infection is usually confined to the intestine. To understand how rotavirus infection might promote diabetes, my group has developed a mouse model. Using mice for these studies ....Our earlier studies in children with a family history of type 1 diabetes have shown that infection with a common virus, rotavirus, may be one factor contributing to their progression to diabetes. Rotavirus is the most common cause of diarrhoea, vomiting and dehydration in young children, and it was thought that rotavirus infection is usually confined to the intestine. To understand how rotavirus infection might promote diabetes, my group has developed a mouse model. Using mice for these studies allows us to control infection and completely analyse the results of infection, which we cannot do in humans. A type of mouse that is very likely to develop type 1 diabetes in its first 6 months of life is infected by mouth with rotavirus. We have shown that these mice develop diabetes 7 weeks faster than the same type of mice that are not given virus. In this project, we will determine the effects of mouse age, virus strain, the number of times infection occurs, and levels of virus growth in the intestine or pancreas on virus-induced diabetes acceleration. The ability of treatments for rotavirus infection, and vaccination against rotavirus, to block this accelerated diabetes also will be tested. We expect that rotavirus will be found growing in the pancreas, that virus growth is necessary for diabetes acceleration, and that prevention of rotavirus infection will also prevent the rapid diabetes onset. This model could prove to be suitable for testing the effectiveness and safety of new drugs and vaccines against both rotavirus and type 1 diabetes. Our studies will be crucial in determining the importance of rotavirus infection in the development of type 1 diabetes.Read moreRead less
Roles Of Integrins In Rotavirus Cell Attachment, Entry And Tropism
Funder
National Health and Medical Research Council
Funding Amount
$339,480.00
Summary
In this project, we aim to discover how rotavirus, the main cause of infantile gastroenteritis, attaches to the surface of cells. Previously, we have shown that rotavirus binds to certain members of the integrin family of proteins on the cell surface. These proteins are intimately involved in cell adhesion, movement, communication and growth. We will continue studies aimed at identifying at the molecular level the requirements for rotavirus interactions with these integrins. It will also be dete ....In this project, we aim to discover how rotavirus, the main cause of infantile gastroenteritis, attaches to the surface of cells. Previously, we have shown that rotavirus binds to certain members of the integrin family of proteins on the cell surface. These proteins are intimately involved in cell adhesion, movement, communication and growth. We will continue studies aimed at identifying at the molecular level the requirements for rotavirus interactions with these integrins. It will also be determined whether expression of these integrins on cells from the intestine, kidney, pancreas and immune system is a requirement for the cells to be infected with rotavirus. Previously, we have shown that rotavirus infection may be linked with progression of at-risk children towards development of type I diabetes, a pancreatic autoimmune disease. This means that understanding how the virus interacts with pancreatic and immune cells is of particular importance. The parts of the virus particle which bind to the integrins will be identified, and these will be produced and tested for their ability to block rotavirus infection in cells and in mice. It is likely that rotavirus binds to integrins by a somewhat different mechanism to that used by other viruses and cellular components. If this is so, then in future it should be possible to design drugs which block virus infection without interfering with the normal function of integrins. This work will also provide data useful for design of rotavirus vaccines, and for improved understanding of the disease process.Read moreRead less
Characterisation Of Rotavirus Vaccine Escape - Potential For Significant Impact On Vaccination Program
Funder
National Health and Medical Research Council
Funding Amount
$531,689.00
Summary
The introduction of rotavirus vaccines have had enormous impact on improving the health of children worldwide. However, the emergence of vaccine escape strains has the potential to significantly reduce the vaccine effectiveness. This study proposes to characterise strains able to escape vaccine protection.
Optimising Rotavirus Vaccine Effectiveness In Aboriginal Children: A Double Blinded Randomised Trial Of Rotavirus Vaccine Given To Infants 6 To 12 Months Old.
Funder
National Health and Medical Research Council
Funding Amount
$2,333,318.00
Summary
Rotavirus is major cause of diarrhoeal illness in children. A vaccine to protect against rotavirus was introduced into Australia in 2006/7. Unfortunately vaccine protection is lowest in those in whom disease rates are highest, including Aboriginal infants in the Northern Territory. This trial will investigate if offering an additional dose of vaccine between 6 to 12 months is an effective way to improve vaccine protection and thereby reduce this disease disparity.