Molecular Hallmarks of Cancer

Molecular Hallmarks of Cancer

Alternative Splicing in Human Disease

Head: Associate Professor Simon Conn

Phone: +61 8404 2816
Email: simon.conn@flinders.edu.au  

Members:
Dr Vanessa Conn
Research Officer

Stuart Webb
PhD student

Kazzem Gheybi
PhD student

Our laboratory is pioneering how alternative gene products drive cancer and other human diseases and act as novel targets for therapy.

Accessing the information embedded in our DNA requires a critical process called RNA splicing. This process is fallible and the resultant products are a diverse group of alternatively spliced RNA molecules comprising the primary source for expansion of the functional proteome. However, many of these RNA transcripts do not code for proteins, so-called non-coding RNAs, and are emerging as the most abundant master regulators of normal cellular processes and even disease (Chen & Conn (2017) Genome Biology 18: 133). Our laboratory focuses on a class of enigmatic non-coding RNAs, called circular RNAs (circRNAs), and continue to publish seminal papers in this field.

CircRNAs are made via a type of alternative RNA splicing called back-splicing, where a downstream splice donor site fuses to an upstream acceptor site, creating a single-stranded, covalently closed circular RNA transcript (Figure 1). Lacking a 5’ cap or 3’ polyadenylation signal the vast majority of these circRNAs are untranslated.

We have found during cellular development, the levels of these circRNAs change and identified an RNA binding protein, called Quaking, which is critical for biogenesis of a large proportion of circRNAs during Epithelial-Mesenchymal Transition (EMT) (Conn et al. (2015) Cell 160: 1125-1134). Also, manipulating these circRNAs can affect the whole organism, including an impact on the alternative splicing of its cognate mRNA (Conn et al. (2017) Nature Plants 3: 17053).

Ongoing projects are examining aspects of circRNA function through profiling their interacting partners. We are utilising a number of human cancer tissue samples, relevant mouse models and in vitro stem cell culture work to assess functions of circRNAs in important biological processes and diseases.

Current research projects/Student opportunities

  • Formation and function of circRNAs in EMT
  • The Molecular Interactome and Functions of Circular RNAs

Postgraduate students with an interest in cutting-edge molecular biology research in cancer can contact Assoc. Prof. Simon Conn to discuss options for higher degree research studies, including PhD, Honours and MS.

Selected recent publications