Populations of viruses in an host can be very diverse and just as the behaviour of a population of humans can be very different to the behaviour of individuals in them, populations of viruses behave differently to the behaviour of individuals in them. This diversity may provide a survival advantage to the virus and it also may regulate the severity of the symptoms in an infected host. This study will provide important new information that will drive vaccine strategies and public health policy.
Biological And Mathematical Studies Of Development Of The Enteric Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$390,250.00
Summary
During very early development in the embryo, cells migrate from the future brain. These cells, called neural crest cells, make there way to the nearest part of the gut, in the future oesophagus. They then migrate as a growing population right along the gut until they have populated the entire gut down to the rectum. To complicate matters, the gut itself is rapidly growing length-wise as this migration occurs. These neural crest cells then form the nerve cells that reside in the gut and which con ....During very early development in the embryo, cells migrate from the future brain. These cells, called neural crest cells, make there way to the nearest part of the gut, in the future oesophagus. They then migrate as a growing population right along the gut until they have populated the entire gut down to the rectum. To complicate matters, the gut itself is rapidly growing length-wise as this migration occurs. These neural crest cells then form the nerve cells that reside in the gut and which control gut function. In a common birth defect, Hirschsprung's disease, this migration stops short of the rectum so that the last part of the gut never develops nerve cells. This region lacking nerve cells is unable to propel the gut contents and, if untreated, this condition of intractable constipation is fatal after birth. Eight genes, when mutated, give essentially the same condition either in humans or animals, but the link between the genes and the condition is still not clear. We have proposed that the genes code for molecules that effect the way the neural crest cells interact with other neural crest cells and with the cells of the gut in which migration takes place. The link between the genes and the development of a normal gut nerve system (or its failure, as in Hirschsprung's disease) operates at the level of the dynamics of the neural crest cell population, interacting with the dynamics of gut growth. This project will use very detailed biological data acquisition to feed into newly formulated original mathematical models to tease out the important links between the neural crest cell population and the growing gut, that control cell migration. This will lead to an understanding of formation of the gut nerve system and of Hirschsprung's disease, at the population level, a level not well served by molecular levels of understanding. These models will have application in the many developmental contexts where cell movement and growth are simultaneous.Read moreRead less
Population Dynamics Of Tissue-specific Effector And Regulatory CD4+ T Cells
Funder
National Health and Medical Research Council
Funding Amount
$394,250.00
Summary
Survival of white blood cells in the body is an active process and is important for the maintainence of a T cell population which can recognise a wide variety of foreign antigens. At present the fate of T lymphocytes which recognise self antigens is unclear. Knowledge of the survival kinetics of self-reactive T lymphocytes and the mechanism by which they are regulated in the normal individual is crucial to be able to control the development of various diseases, including autoimmune diseases. Fro ....Survival of white blood cells in the body is an active process and is important for the maintainence of a T cell population which can recognise a wide variety of foreign antigens. At present the fate of T lymphocytes which recognise self antigens is unclear. Knowledge of the survival kinetics of self-reactive T lymphocytes and the mechanism by which they are regulated in the normal individual is crucial to be able to control the development of various diseases, including autoimmune diseases. From our previous studies of autoimmune gastritis we have generated cell lines of lymphocytes that recognise stomach-specific antigens and with these unique reagents we will perform experiments to determine the fate of these self-reactive T cells in a normal individual. Also we will determine the impact of different amounts of the tissue antigens on the survival and activation of self-reactive T cells, and finally how a special class of lymphocytes, know as regulatory lymphocytes, act in vivo to control the activity of self-reactive T cells. We will use not only classical immunological approaches to address these issues but also state of the art imaging, to visualise the nature of the cell interactions in living tissues. The information arising from this work will underpin strategies to selectively turn off self-reactive lymphocytes that cause disease, will form the basis of clinical development of cell based therapies to treat autoimmune diseases, and the imaging technologies developed in this grant will have wide applicability to the study of a range of immune responses.Read moreRead less
Using Mathematical Models To Assess The Impact Of Interventions To Reduce Sexually Transmitted Infections In Australia
Funder
National Health and Medical Research Council
Funding Amount
$562,276.00
Summary
Sexually transmitted infections (STIs) are an increasing public health problem in Australia. Australia's recent National Transmissible Infections Strategy identified chlamydia control, STI prevention in gay men and STIs in Aboriginal and Torres Strait Islander communities as priority areas. We propose to develop mathematical models of STI transmission and use these to help understand and identify the most cost-effective interventions to reduce the impact of STIs on Australian populations.
An Examination Of The Causes Of Mortality Following Imprisonment In New South Wales Using Data-linkage.
Funder
National Health and Medical Research Council
Funding Amount
$205,500.00
Summary
Prisoner populations are characterised by poor health status including infectious diseases, injury, risk taking behaviours (eg. smoking and self-harm), mental illness, and substance abuse. Serosurveys of blood borne viruses such as hepatitis C and hepatitis B conducted in Australian and overseas prison settings have found that over one third of inmates have been exposed to these viruses with higher rates detected in injecting drug users and female inmates. Few attempts have been made to examine ....Prisoner populations are characterised by poor health status including infectious diseases, injury, risk taking behaviours (eg. smoking and self-harm), mental illness, and substance abuse. Serosurveys of blood borne viruses such as hepatitis C and hepatitis B conducted in Australian and overseas prison settings have found that over one third of inmates have been exposed to these viruses with higher rates detected in injecting drug users and female inmates. Few attempts have been made to examine the causes of mortality among prisoners following release from detention. Most interest has focused on overdoses in the period immediately following release; the aim of this study will examine all causes of death among individuals exposed to the correctional environment and compare these to death rates for NSW. Correctional centres house a largely male (94% in NSW) population with backgrounds of disadvantage in all areas, including Indigenous Australians, people of lower socio-economic status, those with a mental illness, and the intellectually disabled. There are currently over 21,000 (June 2001) prisoners detained in Australian correctional centres with approximately 39% housed in NSW. Fifteen percent of the NSW prisoners are Indigenous but comprise only 2% of the general population. The aims of this project will be to: (1) Identify all causes of death among ex-prisoners in NSW for the period 1985 to 2001; (2). Compare death rates in the study group with those in the NSW community; (3) Correlate pre-release health information contained in medical records with specific causes of death; (4) Compare causes of mortality among various sub-groups eg. injecting drug users, the mentally ill, violent offenders, and the intellectually disabled; (5) Examine causes of mortality between Indigenous and non-Indigenous inmates; and (6) use this information to develop pre-release programmes aimed at reducing excess mortality among this group.Read moreRead less
INVESTIGATING MORTALITY AMONG EX-PRISONERS IN QUEENSLAND: A DATA LINKAGE STUDY
Funder
National Health and Medical Research Council
Funding Amount
$716,801.00
Summary
NOTE: At the time of submitting the NOI for this project we had not yet received feedback from a submission to a parallel NHMRC funding round concerned with social disadvantage. We have since received very positive reviews for the trial foreshadowed in our NOI, and consistent with the recommendations of one reviewer, we have modified our application to complement the proposed trial by conducting a record linkage study. The content area and ethical issues associated with the proposed project rema ....NOTE: At the time of submitting the NOI for this project we had not yet received feedback from a submission to a parallel NHMRC funding round concerned with social disadvantage. We have since received very positive reviews for the trial foreshadowed in our NOI, and consistent with the recommendations of one reviewer, we have modified our application to complement the proposed trial by conducting a record linkage study. The content area and ethical issues associated with the proposed project remain largely unchanged. Studies in Australia and elsewhere have identified a heightened risk of death among ex-prisoners, with drug overdose, suicide and 'accidents' three major causes. Many deaths occur soon after release. Although the high incidence of 'overdose' among ex-prisoners is often attributed to reduced tolerance,most fatal drug overdoses are due to the combined effects of multiple drugs. A detailed understanding of deaths among ex-prisoners is a prerequisite for evidence-based preventive strategies. The proposed study will: (a) Link the identities of prisoners released from custody in QLD between 1994 and 2006, with the National Death Index (NDI). The linked database will permit exploration of the incidence, timing, causes and risk factors for death among ex-prisoners. (b) Compare correctional records of deceased ex-prisoners and a random sample of ex-prisoners known to be alive, focussing on suspected risk factors including criminal history, behaviour in custody, health status, psychosocial adjustment, socio-economic status, and history and treatment for drug use. This will allow more detailed analysis of risk factors for death post-release. (c) Conduct in-depth analysis of causes of death among ex-prisoners, using the National Coroners Information System (NCIS). Information regarding cause and context of death will be coded by a research assistant and analysed to identify group differences (e.g., between ATSI and non-ATSI ex-prisoners).Read moreRead less