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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
Dissecting Apoptosis And IL-15 Dependent Homeostasis Pathways Of Natural Killer (NK) Cells
Funder
National Health and Medical Research Council
Funding Amount
$423,809.00
Summary
We will investigate how the cytokine IL-15 regulates the homeostasis of natural killer (NK) cells. NK cells are critical for immune responses against invading viruses or bacteria or upon detection of transformed cells. NK cells are primed to attack infected or transformed cells and are rapidly activated by direct interaction or by soluble signals. Knowledge of how NK cells development and how their numbers and function are controlled is paramount to understanding infectious disease immunology an ....We will investigate how the cytokine IL-15 regulates the homeostasis of natural killer (NK) cells. NK cells are critical for immune responses against invading viruses or bacteria or upon detection of transformed cells. NK cells are primed to attack infected or transformed cells and are rapidly activated by direct interaction or by soluble signals. Knowledge of how NK cells development and how their numbers and function are controlled is paramount to understanding infectious disease immunology and developing better immuno-therapies.Read moreRead less
Natural killer (NK) cell posses the ability to detect and kill transformed or stressed cells such as tumour cells. My recent data show that NK cells are required for efficient immunotherapy responses by enhancing the global immune response to cancer and preventing tumour cells from metastasising to vital organs. I propose to identify novel pathways and develop new therapeutic approaches to exploit NK cell anti-tumor function and improve cancer immunotherapy response rates in patients.