Global changes in gene expression in hypertension and effects of resveratrol
This project will find all of the genes and pathways involved in a mouse model of hypertension and how the red wine polyphenol resveratrol can influence these.
The red wine polyphenol resveratrol has potent health benefits in various species. This project aims to identify for the first time all of the genes and pathways it affects in human cells, as well as the effects of resveratrol on lifespan in culture. The project will similarly test nicotinamide, which inhibits a key enzyme class that activates these pathways. Then the project will knockdown key transcription factors (FOXOs) that mediate resveratrol’s actions. Changes in mRNA will be confirmed by qRT-PCR. At the end resveratrol will in effect have served as a tool to illuminate the pathways that boost health of human cells. This project allows involvement in new technologies such as gene expression profiling and a variety of molecular biology techniques. The candidate needs to have some background proficiency in molecular biology and academic achievement.
Our research is directed at the molecular basis of hypertension, ageing, cancer and premature birth.
The Lab is Currently engaged in research to discover:
(1) all of the genes whose expression is altered in hypertension
(2) the role of resveratrol in health and its effect on gene expression in hypertension
(3) how certain splicing factors control alternative splicing of pre-mRNA
(4) a role for the (pro)renin-angiotensin system in premature birth
(1) The hypertension studies involve whole-genome microarray of RNA from tissues from genetically hypertensive mice, in collaboration with Prof Geoff Head's Lab at the Baker Heart Research Institute in Melbourne, where radiotelemetry is performed for 24-hour continuous monitoring of cardiovascular parameters, and Dr Ruby Lin and Prof Ian Dawes at the Ramaciotti Gene Function Analysis Centre, School of Biotechnology and Biomolecular Sciences at the University of New South Wales.
(2) Resveratrol is being administered to genetically hypertensive mice and its effect on global gene expression is being monitored, initially in the hypothalamus.
(3) The splicing factors being investigated by the Lab include RBM4 (formerly Lark), ZRANB2 (formerly ZNF265 or Zis), and XE7. The research on these involves their immunolocalization in subnuclear compartments by confocal microscopy, splicing assays and other techniques. Dr Joel Mackay's Lab in the School of Molecular and Microbial Biosciences has extended the ZRANB2 studies to show that the zinc fingers of this protein have a very high specificity for the mRNA 5'-acceptor sequence involved in pre-mRNA splicing [see 2009 publication in PNAS below].
(4) Expression of components of the (pro)renin-angiotensin system - namely (pro)renin, angiotensinogen, angiotensin converting enzyme (ACE), ACE2, angiotensin type 1 receptor (AT1R) and AT2R - in placental tissues is being measured by qRT-PCR on tissues supplied by John Hunter Hospital in a project led by Emeritis Professor Eugenie Lumbers and researchers at University of Newcastle.
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The opportunity ID for this research opportunity is: 1072
Other opportunities with Professor Brian Morris