Regulation Of Gene Expression: Biomolecular Interactions In Cellular Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$2,998,713.00
Summary
This team consists of three of Australia�s younger researchers Merlin Crossley, Joel Mackay and Jacqui Matthews (as Chief Investigators), who are recognized as authorities in the areas of gene regulation and the structural and functional analysis of proteins. They are joined by Mitchell Weiss, a world authority on blood development and clinical disorders,and Alexis Verger, a molecular and cell biologist recruited from France, both as Principal Investigators. Crossley, Mackay and Matthews have wo ....This team consists of three of Australia�s younger researchers Merlin Crossley, Joel Mackay and Jacqui Matthews (as Chief Investigators), who are recognized as authorities in the areas of gene regulation and the structural and functional analysis of proteins. They are joined by Mitchell Weiss, a world authority on blood development and clinical disorders,and Alexis Verger, a molecular and cell biologist recruited from France, both as Principal Investigators. Crossley, Mackay and Matthews have worked as a team for around six years to date, have published together in high-quality international journals, and have received anumber of accolades for their contributions to Australian science. For example, Crossley has won a number of national awards, including the Gottschalk Medal of the Australian Academy of Science; Mackay was recently awarded the Prime Minister�s Prize for Life Scientist of the Year, and Matthews won the only Charles and Sylvia Viertel Medical Research Fellowship to be awarded in 2003. The members of this team have collaborated extensively on the world stage and Crossley, Mackay and Matthews have also taken leadership roles in the Australian scientific community. Mitchell Weiss has been an important collaborator, exchanging reagents and advice, since he and Crossley trained together as postdocs in Stu Orkin�s lab at Harvard in the early 90s. Most recently Weiss, in collaboration with Mackay, has made important discoveries on a-globin production, which has led to several highly significant publications including a seminal paper in Cell in 2004.The program of research put forward in this proposal centres around understanding the mechanisms through which genes are switched on and off, using blood development as a model system, that is also fundamental to human life. The regulation of gene output is essential both during the development of an organism and throughout the course of its life. Problems with this regulation can result in many different disease states, most notably cancer, which includes the many different types of leukemias. At one level, gene output is controlled by networks of specific proteins known as transcription factors that interact both with each other and with DNA. Currently, however, the details surrounding which complexes regulate which genes and the processes that control the making and breaking up of the complexes are not well understood. Knowledge of how these interactions take place will put us in a position to control the output of chosen genes for therapeutic purposes. We propose to use a combination of cell biological, biochemical, and structural approaches to firstly shed light on these complexes and secondly develop reagents that can be used to manipulate the activity of specific genes.Read moreRead less
Periconceptual Foundations For A Healthy Start To Life.
Funder
National Health and Medical Research Council
Funding Amount
$11,022,802.00
Summary
Preconception and early pregnancy is a critical time for a women's health and that of her future child. New research suggests that a woman's genetic potential, her lifestyle and the physical and socioeconomic environment in which she lives, and her biological and social relationship with her male partner, all impact on the long term health of her baby. Abnormal events around the time of conception and in early pregnancy can predispose a newborn to later occurrence, in adult life, of conditions i ....Preconception and early pregnancy is a critical time for a women's health and that of her future child. New research suggests that a woman's genetic potential, her lifestyle and the physical and socioeconomic environment in which she lives, and her biological and social relationship with her male partner, all impact on the long term health of her baby. Abnormal events around the time of conception and in early pregnancy can predispose a newborn to later occurrence, in adult life, of conditions including heart disease, diabetes, obesity and stroke. These adverse events originate in the way that eggs and sperm develop, the uterus is prepared for implantation, the attachment of the early embryo to the lining of the uterus and subsequent growth of the placenta. This Program will study the early life events that promote or limit development of a baby's true potential for successful and healthy life. A better understanding of how lifestyle and environment interact with genes and biology to facilitate optimal growth of the fetus will underpin new preventative measures and therapeutic treatments for infertility, miscarriage and other reproductive disorders. The knowledge gained will inform health policy and clinical practise to improve reproductive health in all Australian women and promote healthy development in all Australian children. The team of researchers is a world-class group of clinicians, scientists and epidemiologists who have made major contributions to our understanding of this area. This team will interface with clinics and hospitals that engage with women prior to and during pregnancy, while having the influence to alter clinical and health practices as well as public health policies. The team will utilize the latest, most technologically advanced laboratory methods and clinical skills, including gene profiling, imaging of early pregnancy, randomised clinical trials and access to the best epidemiological and statistical assessments.Read moreRead less