Month: May 2018

New Paper Published: MASTL overexpression promotes chromosome instability and metastasis in breast cancer

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Very excited to announce that our latest paper entitled “MASTL overexpression promotes chromosome instability and metastasis in breast cancer” has just been published online with Oncogene. You can access the full article for free here:https://www.nature.com/articles/s41388-018-0295-z

Abstract

MASTL kinase is essential for correct progression through mitosis, with loss of MASTL causing chromosome segregation errors, mitotic collapse and failure of cytokinesis. However, in cancer MASTL is most commonly amplified and overexpressed. This correlates with increased chromosome instability in breast cancer and poor patient survival in breast, ovarian and lung cancer. Global phosphoproteomic analysis of immortalised breast MCF10A cells engineered to overexpressed MASTL revealed disruption to desmosomes, actin cytoskeleton, PI3K/AKT/mTOR and p38 stress kinase signalling pathways. Notably, these pathways were also disrupted in patient samples that overexpress MASTL. In MCF10A cells, these alterations corresponded with a loss of contact inhibition and partial epithelial–mesenchymal transition, which disrupted migration and allowed cells to proliferate uncontrollably in 3D culture. Furthermore, MASTL overexpression increased aberrant mitotic divisions resulting in increased micronuclei formation. Mathematical modelling indicated that this delay was due to continued inhibition of PP2A-B55, which delayed timely mitotic exit. This corresponded with an increase in DNA damage and delayed transit through interphase. There were no significant alterations to replication kinetics upon MASTL overexpression, however, inhibition of p38 kinase rescued the interphase delay, suggesting the delay was a G2 DNA damage checkpoint response. Importantly, knockdown of MASTL, reduced cell proliferation, prevented invasion and metastasis of MDA-MB-231 breast cancer cells both in vitro and in vivo, indicating the potential of future therapies that target MASTL. Taken together, these results suggest that MASTL overexpression contributes to chromosome instability and metastasis, thereby decreasing breast cancer patient survival.

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Research Position (Full-time) Available Now.

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Great news, we are looking for a full-time research assistant or junior post-doctoral researcher.

We are seeking a highly motivated BSc (Hons) graduate who is interested in pursuing a career in biomedical research with particular focus on cancer cell biology. The successful applicant will have demonstrated a high level of undergraduate achievement and applicants graduating with Honours will be highly regarded. The successful applicant will work closely with the Principal Hospital Scientist and perform a variety of advanced molecular and cellular biology techniques to elucidate novel mechanisms that drive chromosome instability and drug resistance in breast and lung cancer. Essential criteria include experience in mammalian cell culture, cellular and molecular biology techniques, with experience with mass spectrometry, and/or microscopy and flow cytometry viewed favourably. Candidates should have excellent written and verbal communication skill and a history of publication would be viewed favourably.

The ANZAC Research Institute is situated on the Concord Hospital campus and is affiliated academically with the University of Sydney. The ANZAC Research institute is a multidisciplinary facility, for more information about the institute please see http://www.anzac.edu.au.

This position is open to Australian and New Zealand citizens, permanent residency or people with valid working visa status. It is available for one (1) year initially with prospect of renewal for 3-yrs total, subject to progress and grant applications. Level of appointment will be according to qualifications and experience.

Please apply online via seek and submit the following

Current CV, copy of academic transcript, a cover letter addressing the selection criteria below, provide two current referees, and evidence of work rights within Australia.

Selection Criteria

  • Minimum BSc (Hons I preferred) with a focus on cancer cell biology.
  • Experience in in mammalian tissue culture (transfection, stable cell line production, 3D spheroid culture, gene knockdown/out, CRISPR etc).
  • Experience in molecular and cellular biology techniques (western blotting, PCR, cloning, etc).
  • Experience in Mass Spectrometry (phosphoproteomics), confocal microscopy or flow cytometry will be viewed favourably.
  • Demonstrated capacity to work independently and collaboratively in a team environment
  • Must possess excellent time management, organisational and analytical problem-solving skills.
  • Demonstrate excellent oral and written communication skills.
  • Strong computer software literacy and an understanding of statistics.
  • A history of publication and/or an interest in completing a PhD would be highly regarded.