Kirk Jensen

Kirk Jensen

School of Biological Sciences

Faculty of Sciences


Biography
My research focuses on post-transcriptional gene regulation, and in particular, understanding the roles of RNA-binding proteins (RBPs) in controlling key RNA processing steps, from splicing through to translation initiation.
A long-standing methodological aspect of my work (beginning as a PhD student in Boulder, CO), has been the use of short-wave UV irradiation to induce covalent crosslinks between RBPs and their cognate RNA targets. At the Rockefeller University in New York, I used my knowledge of photo-crosslinking to invent CLIP (crosslinking-immunoprecipitation), a method which uses UV irradiation to covalently link an RBP to its entire cohort of cellular RNA targets in living cells, and which permits the subsequent isolation and sequencing of these linked RNA fragments. CLIP has seen numerous improvements over the years, including an early advance pairing the methodology with high-throughput sequencing (HITS-CLIP), and present-day versions of the technique are considered the gold standard for determining the cellular RNA target repertoire of an RBP.
My current research at SAHMRI focuses on translation initiation. The canonical translation initiation pathway is orchestrated by the eIF4E1 protein, which concurrently binds the m7G cap at the 5' end of the mRNA and the scaffolding protein eIF4G. Together these interactions permit the deposition of the 43S pre-initiation complex at the 5' end of the mRNA; once the AUG has been found though scanning, translation itself begins.
A major goal is to better understand how translation initiation (and specifically eIF4E1) is modulated by the Ras-MAPK and mTOR/mTORC1 signalling pathways, as these pathways can directly modify eIF4E1 itself or its binding partners (phosphorylation of eIF4E1 by the MNK kinases, phosphorylation of the 4E-BPs by mTORC1), or modify other core translation initiation factors (phosphorylation of S6K by mTORC1, for example). A second goal is to understand the function of the alternative human cap-binding protein, eIF4E2. While several lines of investigation indicate that eIF4E2 acts as a translational repressor (by interfering with the initiation function of eIF4E), other evidence suggests eIF4E2 supports translation, but only under conditions of cellular stress.
To address both of these goals, we are developing novel CLIP-like methodology to identify the cellular cohorts of mRNAs bound in vivo by either eIF4E1 or eIF4E2 under a wide range of environmental conditions, including inhibition of MNK and/or mTORC1 signalling using highly selective small molecule kinase inhibitors. Bioinformatic analysis of this set of specific eIF4E1 ‘cap-omes’ will permit the identification of those mRNAs which are strongly regulated by MNK and mTOR signalling and may also give us significant insight into the mechanisms which underlie the changes in translation of individual mRNA species. Similarly, analysis of the eIF4E2 ‘cap-omes’ should allow us to state with certainty if eIF4E2 acts as a repressor or as an activator of (an alternative pathway) of translation initiation, and by evaluating the environments in which we observe either (or both) activities we should develop a good understanding of the cellular contexts where eIF4E2 function is most critical, and why.

Please see my Researcher Profiles at SAHMRI, ORCID, and Scopus
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  • Appointments

    Date Position Institution name
    2016 Affiliate Associate Professor University of Adelaide
    2016 Senior Research Fellow South Australian Health and Medical Research Institute
    2004 - 2015 Senior Lecturer University of Adelaide
    2001 - 2003 Research Assistant Professor Rockefeller University
  • Education

    Date Institution name Country Title
    1991 - 1995 University of Colorado Boulder United States PhD (Chemistry and Biochemistry)
    1983 - 1997 Stanford University United States BS (Biological Sciences)
  • Postgraduate Training

    Date Title Institution Country
    1996 - 2001 Postdoctoral Fellow Rockefeller University United States
    1996 - 1996 Postdoctoral Associate University of Colorado Boulder United States
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  • Past Higher Degree by Research Supervision (University of Adelaide)

    Date Role Research Topic Program Degree Type Student Load Student Name
    2015 - 2017 Co-Supervisor Novel Roles of the MAP Kinase - interacting Kinases Doctor of Philosophy Doctorate Full Time Miss Shuye Tian
    2013 - 2014 Principal Supervisor PSC1: A PROTEIN WITH MULTIPLE ROLES IN RNA METABOLISM Doctor of Philosophy Doctorate Full Time Ms Philippa Davey
    2011 - 2013 Principal Supervisor Identification of Protein-RNA and Protein-Protein Interactions by the Neuronal HuC Protein of Mus musculus Master of Philosophy Master Full Time Mr Bradley Simpson
    2007 - 2011 Principal Supervisor Investigating Mechanisms of Post-transcriptional Gene Regulation in the Germ Cells of Zebrafish Doctor of Philosophy Doctorate Full Time Miss Sophie Wiszniak
    2007 - 2011 Co-Supervisor Sox3 Dosage Regulation is Important for Roof Plate Specification during Central Nervous System Development Doctor of Philosophy Doctorate Full Time Mrs Kristie Rogers
    2005 - 2011 Principal Supervisor Investigation into The Molecular Function of The Neuronal Hu RNA Binding Protein, HuCsv1 Doctor of Philosophy Doctorate Full Time Mr Peter McCarthy
    2002 - 2005 Co-Supervisor Investigating the Role of EphA/ ephrin-A Signalling During Trigeminal Ganglion Axon Guidance Doctor of Philosophy Doctorate Full Time Ms Chathurani Jayasena

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