SCRIB acts as an oncogene in T-ALL by activating signaling pathways that control proliferation

The focus of this project is SCRIB, a component of the Scribble polarity complex. SCRIB has been implicated in multiple epithelial cancers but its role in haematopoietic malignancies is largely unknown. Previous studies in our laboratory using a mouse model of T-cell Acute Lymphocytic Leukaemia (T-ALL) have shown SCRIB acts as an oncogene.

We have analysed proteins that are up- or down-regulated upon loss of SCRIB in T-ALL through a reverse phase protein array (RPPA). This project will investigate one or two key intracellular signaling pathways to discern how loss of SCRIB delays the onset of T-ALL.

We will confirm RPPA data with western blot and quantitative RT-PCR and will investigate signaling pathway members altered upon loss of SCRIB with RNA seq. The distribution of key signaling proteins in different haematopoietic fractions as well as the levels of proliferation/apoptosis will be examined with flow cytometry and immunohistochemistry (IHC) including multiplex IHC. Depending on the length of the degree, the applicant will undertake additional assays to dissect the role of SCRIB in T-ALL including tissue culture, live cell microscopy, intravital microscopy, and colony assays.

This project is a collaboration across the Immunology program together with the Advanced Microscopy & Histology Core Facility. The principle supervisor is also head of the Advanced Microscopy & Histology Core Facility.
https://www.petermac.org/research/core-facilities/centre-advanced-histology-microscopy

Peter MacCallum Cancer Centre, Melbourne Australia
Peter MacCallum Cancer Centre is Australia’s only public hospital solely dedicated to cancer, and home to the largest cancer research group in Australia. Cancer is a complex set of diseases, and modern cancer research institutes such as Peter Mac conduct research covering a diversity of topics that range from laboratory-based studies into the fundamental mechanisms of cell growth, translational studies that seek more accurate cancer diagnosis, clinical trials with novel treatments, and research aimed to improve supportive care.
All students engaged in postgraduate studies at Peter Mac are enrolled in the Comprehensive Cancer PhD (CCPhD) program, regardless of which university they are enrolled through. The program is managed by the Sir Peter MacCallum Department of Oncology (The University of Melbourne), based at Peter Mac.

Tapping into the depth and breadth of knowledge and experience offered by the ten partners of the Victorian Comprehensive Cancer Centre (VCCC) alliance, the University of Melbourne’s Comprehensive Cancer PhD Program provides a unique opportunity for multidisciplinary cancer-related PhD candidates to experience clinical and research activities across the alliance.

The Comprehensive Cancer PhD program builds on established conventional training for cancer research students providing a coordinated program of skills, research and career training in addition to usual PhD activities. The program is designed to complement existing PhD activities and provides opportunities to develop professional skills that will help candidates to fulfil their career ambitions.
https://www.petermac.org/education/comprehensive-cancer-phd-program