The same but different: Transcriptional responses to inflammatory stimuli in phenotypically discordant monozygotic twins

Research Opportunity
Honours, Master of Biomedical Science
Number of Honour Places Available
1
Number of Master Places Available
1
Department
Paediatrics
Location
Royal Children’s Hospital/Murdoch Childrens Research Institute
Primary Supervisor Email Number Webpage
Professor Richard Saffery richard.saffery@mcri.edu.au Personal web page
Co-supervisor Email Number Webpage
Professor David Burgner david.burgner@mcri.edu.au 99366730 Personal web page
Doctor Boris Novakovic boris.novakovic@mcri.edu.au 83416341

Summary This project will examine the transcriptional response of purified blood monocytes to inflammatory stimuli in vitro in twins discordant for weight from birth to 6 years of age. As monozygotic twins are genetically identical, any differences in response will be directly attributable to cumulative environmental exposures, allowing the relative contribution of genes and environment to this important aspect of immune cell function to be directly assessed.

Project Details

The term 'epigenetics' literally means 'above DNA' and refers to the study of molecular interactions that influence chromosome structure and gene activity. We can think of epigenetic marks as signals that determine whether a stretch of DNA is 'open for business' and accessible for regulatory factors or 'closed' and therefore inaccessible. A key property of many epigenetic marks is that they not only indicate the state of the cell at a set point in time, but can also carry 'memories' of past exposures, with the potential influence cellular responses to future stimuli. Therefore, the epigenome (the complete epigenetic profile of a cell) contains information about the 'past, present, and future' of a cell or tissue. Understanding the relative roles of genetic and environmental influence to epigenetic variation is important in many aspects of human health, particularly the immune system.   Inflammation is a key outcome of the immune response to exogenous 'foreign' stimuli and is also a feature of excessive weight in children and adults. This project will examine the transcriptional response of purified blood monocytes to inflammatory stimuli in vitro in twins discordant for weight from birth to 6 years of age. As monozygotic twins are genetically identical, any differences in response will be directly attributable to cumulative environmental exposures, allowing the relative contribution of genes and environment to this important aspect of immune cell function to be directly assessed. The project will be laboratory-based and will involve will stimulating peripheral blood monocular cells and purified monocytes, profiling cytokine release and transcriptional response via single-cell RNAseq and bulk RNAseq. It is anticipated that the results will form the basis of a future publication.



Faculty Research Themes

Child Health

School Research Themes

Child Health in Medicine



Research Opportunities

Honours, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Paediatrics

Research Node

Royal Children’s Hospital/Murdoch Childrens Research Institute

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