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The major area of research undertaken by our laboratory are the molecular mechanisms of regulation of apoptosis (physiological cell death), within the bounds of reproductive biology. Our laboratory has cloned several cell death associated genes in the rabbit ovary. In addition to aspects of reproductive biology, research in 'apoptosis' has numerous applications in conditions such as 'cancer, wound dealing, general tissue turnover and remodeling'. We employ a variety of techniques and models throughout our investigations.
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The corpus luteum has intrinsic mechanisms for its own regulation, mechanisms that we are only beginning to understand. Since it is an ephemeral gland, the corpus luteum has unusual requirements-it must prepare for its own destruction (luteolysis) while fulfilling its critical role of progesterone secretion. Although many factors have been identified which play important roles in CL regression, the cellular mechanisms associated with luteolysis are unclear. A report using the bovine ovary has indicated that the regressing CL exhibits internucleosomal DNA cleavage, characteristic of cell death by apoptosis, although the occurrence of apoptosis in this species is correlated only with structural regression. The precise role of apoptosis in functional as well as structural luteolysis, and the hormonal regulation of this process, remain to be elucidated. In the last three decades, it has been well established that cell death plays important roles in physiological as well as pathological events. Organogenesis during fetal life has been shown to proceed appropriately by cell proliferation to form certain structures, which may be accompanied by cell death. Cell numbers in tissues of the body are correctly maintained by balancing cell production with cell death. Even in malignant tissues, the correlation between the rate of enlargement of various neoplastic tissues and of their cell generation can not be explained without a consideration of cell death. Historically speaking, Bassis (1964) first noted that accidental cell death due to environmental perturbation may differ fundamentally in mechanism from natural cell death in cell turnover. This discrimination between two major types of cell death provided some clue to the possibility of different mechanisms in the dying processes of cells. In 1972 cell death was classified into two categories-apoptosis and necrosis, based on morphological observations. Apoptosis is a mode of physiological cell death that permits the selective removal of a discrete population of cells in the absence of an immune response or inflammatory reaction. Cells dying by apoptosis exhibit a characteristic series of intracellular events including nuclear and cytoplasmic condensation, membrane blebbing and the release of apoptotic bodies from the dying cell that are phagocytosed by neighboring cells. One of the precipitating events associated with the onset of apoptosis is the cleavage of nuclear, but not mitochondrial DNA at internucleosomal sites which generates DNA fragments in size multiples of approximately 185-basepairs, the size of one nucleosomal unit. This characteristic feature of internucleosomal DNA cleavage has been widely used as a marker for apoptotic cell death in essentially all tissues examined. Recent biochemical studies have indicated that the up-regulation of early growth response gene expression normally observed to occur during cell cycle progression is also detected during apoptosis, suggesting that cellular proliferation and death may be linked by common signaling mechanisms.
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Over recent years this work has been funded by the generous contributions of the following organization's. Details of each are provided below, funding shared between investigators is denoted were applicable by an asterix.
Specific Grant Outlines: 1/9/87-31/8/1987. Quantitative histological and physiological studies of the rabbit corpus luteum using an in vitro perfusion system. Lalor Foundation. $40,000 1/10/1988-30/9/1989*. Angiogenesis and the development of the rabbit corpus luteum. Institutional Research Grant. $10,000 1/1/1989-30/1/1992. Histological and physiological regulation of rabbit corpus luteum. Rockefeller Foundation. $190,000 1/9/1989-31/8/1990. Effects of an analog of gonadotropin-releasing hormone treatment on rabbit ovarian function: quantitative histological and physiological studies. IRGPC. $10,000 1/9/1989-31/5/1993*. Effects of an analog of gonadotropin-releasing hormone treatment on ovulation and corpus luteum function: quantitative histological and physiological studies. Lalor Foundation. $40,000 1/5/1989-30/4/1990*. Cocaine: Effects on corpus luteum structure and function in the pregnant rabbit. $ 10,000 1/11/1990-31/10/1991*. Corpus luteum maintenance and regression in the rabbit:quantitative structure-function relationships. IRGPC. $10,000 1/3/1988-31/12/1993*. Ovulation-Studies using in vitro perfused ovaries. 5 RO1 HD19430-07. $420,227 (direct cost) 1/7/1992-30/6/1997*. The Hopkins Population Center. 2P30 HD06268. $400,000 (direct cost) 1/6/1993-30/5/1995*. Insulin-like growth factor-I regulation of corpus luteum function. Stetler Research Fund for Women Physicians. $40,000 * Ovulation-studies using in vitro perfused ovaries. NICHD-19430. $583,113 1/11/1993-30/10/1994*. Insulin-like growth factor-I regulation of corpus luteum function. IRGPC. $12,000 1/7/1994-30/6/1995*. Ovulation, follicle rupture, oocyte maturation and establishment of the corpus luteum. Rockefeller Foundation. $46,300 1/5/1993-30/6/1994*. Regulation of physiological cell death in the corpus luteum. IRGPC. $12,000 1/1/1995-31/12/1996.
Role of IGF-I in corpus luteum function. Australian Research Council. 1/1/1996-31/12/1998. Regulation of apoptosis during corpus luteum regression. National Health and Medical Research Council. $135, 000 1/1/1996-31/12/1998. Role of apoptosis in aging of the female reproductive system. Raine Medical Research Foundation. $96,325 1/1/1998-31/12/1998.
Role of nitric oxide in the control of ovulation. Australian Research
Council. 1998*. NH&MRC Equipment Grant. $80,000 1/1/1999-31/12/1999. Apoptosis-associated signaling pathways in follicular atresia. Australian Research Council. $17,000 2000*. NH&MRC Equipment Grant. $70,000 1/1/00-31/12/00. Role of Y81 (A frizzled related protein) in Ovulation and Interaction with Nitric Oxide. University of Western Australia Research Grant. $14,000 1/1/01-31/12/01. Tumour necrosis factor-a signal transduction in corpus luteum apoptosis. Australian Research Council. $10,000 1/1/01-31/12/01*. Examining Proliferation and Apoptosis in the Placenta during Development and Pre Eclampsia. Women's and Infants Research Foundation (WIR). $15,000 1/1/99-31/12/03*. The role of GnRH on corpus luteum apoptosis. National Institute of Health (NIH, USA). US$48,000 1/1/02-31/12/02. Proliferation and Apoptosis in the Placenta during Development and Pre Eclampsia. West Australian Institute of Medical Research (WAIMR). $26,500
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The list below details my involvement in the academic and greater scientific community. This includes service within the University structure, positions on editorial boards, international/national journal reviews, service on funding panels, and my involvement in the organization and programming of national and international conferences. School of Anatomy & Human Biology - The University of Western Australia In addition to routine participation in all Academic Staff meetings, I have taken on several administrative duties in the school. I have served as a member on a number of committees.
Faculty of Science/Medicine - The University of Western Australia
The University of Western Australia I have served and continue to serve on several University Committees, I have been a member of the following University Committees:
Johns Hopkins University, Baltimore, USA
Editorial Boards
Adhoc Grant Reviewer
Conference Organizing Committee
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