Genetic And Phyisological Regulation Of KIR2DL4 Expression
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
Genetic mutations occur frequently but most are deleterious and are lost from the population. Advantageous mutations are selected for and eventually replace the original gene. However, some mutations are advantageous under one set of circumstances and disadvantageous under others. These mutations often reach a high frequency in the population and are maintained along with the original gene. An example of this situation is the mutation in the haemoglobin gene that causes sickle cell anaemia. A si ....Genetic mutations occur frequently but most are deleterious and are lost from the population. Advantageous mutations are selected for and eventually replace the original gene. However, some mutations are advantageous under one set of circumstances and disadvantageous under others. These mutations often reach a high frequency in the population and are maintained along with the original gene. An example of this situation is the mutation in the haemoglobin gene that causes sickle cell anaemia. A single copy of the mutant gene protects against malaria (advantageous) but a double dose of the gene results in sickle cell anaemia, which is fatal. Both the mutant and original gene are maintained in the population as the number of people dying from sickle cell anaemia is less than the number who would die from malaria if the mutant gene did not exist. This phenomenon is known as balancing selection. There are many examples of balancing selection and for each example there is usually a medical condition associated with a double dose of the mutant gene. We have discovered a new example of balancing selection in one of the genes used by the immune system. Very little is known about the function of this gene. In fact the literature abounds with contradictory findings concerning this gene. Our discovery that a mutant gene is present at very high frequency in the population helps explain these contradictory findings and places us in a very strong position to achieve a much better understanding of the function of this gene. We propose to investigate the basic biology of this gene and how it used in the immune system in order to obtain clues as to which medical condition this mutation may be relevant to.Read moreRead less
Role Of NK Receptors In Susceptibility And Resistance To Human Malaria
Funder
National Health and Medical Research Council
Funding Amount
$546,588.00
Summary
Malaria kills 2 million children every year. However, many eventually become resistant to the disease. What causes some kids to die, and how others become resistant, is unknown. We believe that genes for Natural Killer molecules in the immune system can protect people against malaria, but can also over-react in the wrong way and make things worse. We plan to investigate the role of Natural Killer genes in causing disease and also protecting in young children in Papua New Guinea against malaria.
Host Resistance And Protection Against Oral Candidasis
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Candida albicans is an important opportunistic pathogen, that is widely represented in general medical and dental practice, as well as in the hospital environment. Clinical observations indicate that defects in innate immunity predispose patients to disseminated infection, whereas a weakened cell-mediated immune response is commonly associated with chronic oral infections. Animal models of both chronic and acute oral candidiasis have been developed and characterised by the applicants, and these ....Candida albicans is an important opportunistic pathogen, that is widely represented in general medical and dental practice, as well as in the hospital environment. Clinical observations indicate that defects in innate immunity predispose patients to disseminated infection, whereas a weakened cell-mediated immune response is commonly associated with chronic oral infections. Animal models of both chronic and acute oral candidiasis have been developed and characterised by the applicants, and these have clearly implicated T cells in the process of recovery from primary infection. The models will now be used to analyse the effector mechanisms that lead to clearance of the yeast from the oral cavity, with a particular focus on the role of phagocytic cells, and their interaction with T cells. The acute model will be used to identify immunological variables that can act as markers of protection, and the effectiveness of therapeutic manipulations will be evaluated in the chronic model, with the ultimate aim of developing a protective vaccine for human infections.Read moreRead less
Structural And Functional Investigation Of Killer-Cell Immunoglobulin-like Receptors
Funder
National Health and Medical Research Council
Funding Amount
$546,966.00
Summary
Natural Killer (NK) cells are an important component of the immune response to cancer and infection. This project will define the molecular targets that are recognised by NK cells. This knowledge can then be used as a guide in the selection of bone marrow donors in the treatment of leukaemias as well as understanding how we fight infections.
Mechanisms Of Virally-induced Immunosuppression: Effects On DC-NK Networks
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Cytomegalovirus (CMV) infection induces immunosuppression that often results in adverse clinical outcomes. Our previous work established that dendritic cells (DC), cells involved in the initiation of immune responses, are a principle target for CMV. This proposal will test the hypothesis that CMV-induced immunosuppression is mediated by viral interference with DC. Understanding the mechanisms involved in the induction of immunosuppression is a crucial step towards developing better therapies.