Novel mechanisms for gene regulation in ageing
Summary
Discovery of novel mechanisms for gene regulation in health and disease in relation to ageing and its associated clinical conditions such as hypertension and cancer.
Supervisor(s)
Research Location
Program Type
Masters/PHD
Synopsis
Splicing factors: To identify novel splicing factor mechanisms and interactions. This will involve a broad array of molecular biology techniques as well as confocal imaging using specific antibodies to track proteins of interest within the cell. The effect of resveratrol on alternative splicing will be persued.
Hypertension: To identify genes whose expression is altered in spontaneously hypertensive mice. This will use microarray technology and extracts of key tissues such as kidney, adrenal, heart, blood vessels and hypothalamus. The response to resveratrol will also be tested.
Additional Information
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
More specifically:
(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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Keywords
molecular biology, splicing factors, renin, longevity, Hypertension, gene expression profiling, resveratrol, microarrays
Opportunity ID
The opportunity ID for this research opportunity is: 671
Other opportunities with Professor Brian Morris
- Global effects of resveratrol on gene expression and senescence.
- The splicing factor RBM4 in cancer and other diseases
- Global changes in gene expression in hypertension and effects of resveratrol
- The splicing factor RBM4 in cancer and other diseases
- The splicing factor RBM4 in cancer and other diseases