The Role Of The PRB/E2F Pathway In Erythropoiesis And Cell Cycle Control
Funder
National Health and Medical Research Council
Funding Amount
$272,036.00
Summary
Circulating blood contains two major types of cells. Red blood cells supply the oxygen required by all cells in our body to survive and white blood cells protect our body from invasion by foreign organisms. The balance in the number of these cells in our blood is a carefully regulated process which, when disturbed, can lead to a number of life-threatening blood diseases. Uncontrolled overgrowth of blood cells results in a particular type of cancer known as leukaemia. In contrast, when there is a ....Circulating blood contains two major types of cells. Red blood cells supply the oxygen required by all cells in our body to survive and white blood cells protect our body from invasion by foreign organisms. The balance in the number of these cells in our blood is a carefully regulated process which, when disturbed, can lead to a number of life-threatening blood diseases. Uncontrolled overgrowth of blood cells results in a particular type of cancer known as leukaemia. In contrast, when there is an insufficient number of red blood cells, not enough oxygen reaches cells from the brain and other vital organs and results in a condition known as anaemia. We have genetically engineered a mouse that lack the protein known as E2F4 and is unable to produce enough red blood cells and suffers from anaemia. This protein, E2F4, controls genes essential for the decision of cells to start or stop growing and multiplying. The E2F4-deficient mice therefore provide a new and powerful model to understand the mechanism by which disturbance of red blood cell numbers can lead to diseases such as leukaemia and other diseases of the blood. Identification of the genes controlled by E2F4 may provide new targets for the development of therapeutic drugs to combat these diseases.Read moreRead less
Reproduction is dependent upon the secretion of gonadotropin releasing hormone (GnRH) from the brain, that stimulates gonadotropin synthesis and release from the pituitary gland. In turn, GnRH and gonadotropin secretion is controlled by feedback effects of gonadal steroids such as estrogen. Various neural systems regulate GnRH cells. Kisspeptin is a recently discovered neuropeptide that appears to play a major role in the regulation of GnRH cells. Because it is newly recognized, the significance ....Reproduction is dependent upon the secretion of gonadotropin releasing hormone (GnRH) from the brain, that stimulates gonadotropin synthesis and release from the pituitary gland. In turn, GnRH and gonadotropin secretion is controlled by feedback effects of gonadal steroids such as estrogen. Various neural systems regulate GnRH cells. Kisspeptin is a recently discovered neuropeptide that appears to play a major role in the regulation of GnRH cells. Because it is newly recognized, the significance of kisspeptin and the relevant receptor, GPR54, is not well defined. This project aims to use our unique combination of abilities to determine the significance of kisspeptin in the regulation of GnRH and gonadotropin secretion. We will study both sheep and monkey brains, measuring gene expression for kisspeptin and GPR54 in a range of physiological states and we will determine how kisspeptin acts on GnRH cells. We will determine whether kisspeptin plays a role in the feedback effects to GnRH cells. Effects on the pituitary gland will also be studied. We will use sheep models to measure kisspeptin effects on GnRH secretion, because this cannot be done in the monkey or the rodent. We will examine the function of kisspeptin and GPR54 in relation to puberty. We will also use a model of puberty (seasonal breeding in the sheep) to determine whether activation and quiescence of the reproductive system is related to the function of kisspeptin and GPR54. This work will define the role of kisspeptin in the regulation of reproduction.Read moreRead less