Bogoyevitch laboratory: Regulatory biology

  • Head of Laboratory

    Associate Professor Marie Bogoyevitch
    T: +61 3 8344 2289
    E: marieb@unimelb.edu.au
    Location: Cell Signaling Research Laboratories, Level 5 West, Medical Building, Grattan Stree
    W: Personal web page

Research Overview

The Bogoyevitch research team is interested in signal transduction, i.e. the mechanisms of intracellular communication pathways. We are specifically evaluating the regulation of protein kinases, transcription factors and microtubule regulatory proteins to improve our understanding of the roles they play in health and disease.

We study the intracellular signalling pathways that regulate the responses of cells to changes in their environment, some of which are associated with dramatic alterations in gene expression.

In particular, we are studying how changes in the level of the transcription factor STAT3 affect its localisation to the nucleus and regulation by phosphatases, as well as the profiles of gene expression in response to cytokines or environmental stresses.

The importance of STAT3 has been emphasised by its continued implication as a key player in cancer and inflammation.

Our recent microarray analysis has revealed the complexity of gene expression outcomes regulated by STAT3. We are now defining the underlying mechanisms for differential STAT3 spliceform regulation by asking questions such as:

  • What are the protein binding partners for STAT3?
  • What does live-cell imaging reveal about the movement of STAT3 into and out of the nucleus?
  • What is the basis for the gene repression by STAT3?

scheme showing differential transcriptome profile by STAT3 spliceforms before and after cytokine stimulation

Differential transcriptome profile by STAT3 spliceforms before and after cytokine stimulation (Ng et al, Biochem J 2012).

We are interested in how JNK-mediated phosphorylation impacts on the functions of microtubule-regulatory proteins such as DCX. We are asking questions such as:

  • How does JNK recognise these proteins?
  • What are the phosphorylation sites?
  • What is the ultimate impact of these changes on cell functions including survival, morphology and movement?

primary cultures of cortical neurons showing differential staining

Primary cultures of cortical neurons stained for nuclei (blue), tubulin (red), DCX (green) (Wei-Kai Chen et al, unpublished).

We are aiming to identify the broader range of JNK-interacting proteins. Using a combination of biophysical and cell biology approaches we are asking questions such as:

  • What is the basis for this use of a share interaction site?
  • Can we manipulate binding to favour specific interactions?
  • What are the outcomes of these altered interactions for cellular outcomes?
  • Do the outcomes underlie the development of diseases including stroke, diabetes and cancer?

scheme showing docking site for multiple different JNK binding proteins

A general scheme depicting the use of a common docking site for multiple different JNK binding proteins, including upstream kinases, phosphatases, scaffolds and substrates.

Current project areas

  1. STAT3 spliceform regulation to influence downstream gene targets in cancer
  2. Kinase regulation of the cell cytoskeleton
  3. Mapping mutant protein function in neurodegeneration
  4. Molecular jousting in viral infection
  5. Impact of  kinase trafficking in the cytoplasm and nucleus

Anyone interested in any of these projects should contact Associate Professor Marie Bogoyevitch directly for further information.
T: +61 3 8344 2289
E: marieb@unimelb.edu.au

Staff

  • MengJie Hu, PhD Student
  • Maryam Moslehi, PhD Student
  • Vincent Tano, PhD Student
  • Sunyuan Zhang, PhD Student

Research Publications

Click here for the results of a PubMed search of Marie's publications.

Click here for the results of a Google Scholar analysis of Marie's publications.