Dysregulation of cardiac conduction and its effect on the cellular landscape of the mammalian heart

Research Opportunity
PhD students, Honours students, Master of Biomedical Science
Number of Honour Places Available
Number of Master Places Available
Primary Supervisor Email Number Webpage
A/Prof KELLY SMITH kelly.smith1@unimelb.edu.au

Summary The focus of the Smith group is to identify the genetic and cellular processes that regulate heart development. The heart develops by differentiating and integrating multiple tissue types via a specific sequence of events to generate the stereotypical structure of the organ. The fact that this structure is more or less identical between individuals demonstrates that a tightly controlled genetic program instructs this process. The lab is interested in identifying the genes in this program, determining how they function and uncovering the cellular processes they regulate. We use the zebrafish model for much of our discovery-based projects. The zebrafish is an excellent genetic model and the transparency of the embryos and availability of fluorescent transgenic reporter lines permits live imaging of organogenesis. For particularly important projects, we translate our discoveries to the mouse models to investigate evolutionary conservation. The long-term objective of the lab is to contribute to our knowledge of how to build a heart, gathering along the way information that will assist bioengineering efforts and help with diagnosis and treatment of genetic-based heart disease.

Project Details

A rhythmic heartbeat is essential for survival. The cardiac conduction system (CCS) is a specialised network of electrical tissue distributed throughout the heart, carrying electrical signals to control the timing of heart contraction. This occurs in tandem with cardiomyocytes in the myocardium, which cannot spontaneously beat, but are electrically competent. The coordinated beating of the heart relies on electrical currents being established and propagated, via junctions between cells and pores within cells. Any defects that affect the capacity of the CCS or myocardium to initiate or propagate these electrical currents, can result in cardiac arrhythmia. Our lab identified a novel gene, tmem161b, as part of a genetic screen in zebrafish and mutation of tmem161b has been shown to cause abnormal electrical conduction of the heart. Importantly, preliminary data establishes a similar requirement for Tmem161bin the mouse. We hypothesize that loss of Tmem161b will cause a change in the cellular landscape of the heart, impacting ion transport across cells and consequently, cardiac conduction. In this project we will use in vivo and in vitro methodologies to investigate how this important new regulator functions at the cellular and sub-cellular level, by assessing the availability, localization and distribution of macromolecules involved in ion transport (such as ion channels and gap junctions), and examine its effects on the cytoskeletal network, focal adhesions and the extracellular matrix. Methods used in this project will include genetic crosses, mouse embryology and microdissection, electron microscopy and image analysis, cell culture, transfection using plasmid constructs, immunofluorescence, confocal microscopy and analysis.

Research Opportunities

PhD students, Honours students, 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.

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