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
Hematopoietic Effects Of Activating The Hedgehog Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$410,551.00
Summary
The hedgehog proteins are important for normal human development. They are expressed on cells of the brain and developing limbs and provide important signals to neighbouring cells so that development of the brain and limbs can occur normally. Mutations in genes within the hedgehog signalling pathway lead to congenital abnormalities such as failure of the brain to fold properly and shortened limbs or extra digits. Hedgehog proteins also stimulate the growth of adult stem cells that are responsibl ....The hedgehog proteins are important for normal human development. They are expressed on cells of the brain and developing limbs and provide important signals to neighbouring cells so that development of the brain and limbs can occur normally. Mutations in genes within the hedgehog signalling pathway lead to congenital abnormalities such as failure of the brain to fold properly and shortened limbs or extra digits. Hedgehog proteins also stimulate the growth of adult stem cells that are responsible for the maintenance of many adult tissues such as the skin, bone and hair. Excessive hedgehog signalling however can lead to cancers, particularly of the brain and skin. The ability of hedgehog proteins to stimulate the growth of stem cells raises their use for expansion of stem cells. This would be particularly useful for umbilical cord blood stem cells, which could be used to treat patients with leukemia if there were sufficient numbers. This project will examine the potential use of hedgehog proteins for stimulating blood stem cells.Read moreRead less