Discovering molecular targets to treat ovarian cancer
Value
$32,500 per year (RTP Stipend rate, indexed annually); additional funds ($7.5k) during the course of the PhD for travel and other PhD-related expenses.
Duration
3.5 years
Status
Closed
Opens
11/05/2023Closes
01/11/2023Overview
Background: Ovarian cancer is the leading cause of death from gynaecological malignancies. Subtypes with mutations in a member of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodelling complex are particularly chemoresistant.
Hypothesis: A precision medicine approach combining unbiased and targeted screening methods focused on the SWI/SNF chromatin remodelling complex will yield breakthrough opportunities to treat cancers with mutations in genes encoding members of this complex.
Aims:
(1) Use unbiased whole-genome CRISPR (clustered regularly interspaced short palindromic repeats) knockout and activated CRISPR screens to identify new targets with the potential to treat ovarian cancer with mutation of a SWI/SNF complex member.
(2) Use targeted screening approaches to inhibit aberrant functions of mutant SWI/SNF complex and identify drugs that can be repurposed to treat ovarian cancer with these mutations.
Research Methodology: This project will include working with CRISPR-engineered ovarian cancer cell lines. It will involve working on CRISPR knockout and activated CRISPR library screens to look for synthetic lethal combinations for cells with a mutation in a gene encoding a SWI/SNF complex member. Cloning of targets will also be undertaken to investigate the functional consequences of overexpression of candidates. Functional assays will be conducted in 2D and advanced 3D bio-printed systems. These will include assays to determine cell proliferation, death, migration, invasion etc. Library drug screens will be undertaken in these models.
Outcomes: This work will discover new opportunities to treat ovarian cancer with mutation of genes encoding SWI/SNF complex members. There is strong potential for rapid clinical impact with the discovery of drugs with the capacity to be repurposed to treat ovarian cancer.
Who is eligible?
Applicants must be either permanent Australian residents or New Zealand citizens. To be eligible for this application, applicants must have completed a UTS recognised you must hold the following or equivalent degree in
- MSc Research or MSc Coursework with a research thesis of at least 6 months.
- Bachelor Honours degree with First Class, or Second Class Division 1, or division 1 honours, or an equivalent or higher qualification, or submitted other evidence of general and professional qualifications that demonstrates potential to pursue graduate research studies.
Essential:
A First Class (or Second Class, Division 1) honours degree (or equivalent) on a topic related to health and/or medical research.
Examples of scientific writing assessed to be of a high quality. This may be from undergraduate subjects or the candidate's honours year.
The ability to communicate their science to an audience of peers and academics.
The ability and willingness to be an engaged team member of a laboratory group consisting of members at all career stages, from intern to Professor.
Strong planning and organisational skills.
Basic laboratory skills including accurate pipetting, mathematical ability to enable the calculation of dilutions etc.
Basic understanding of statistics used for the analysis of scientific data (e.g. ANOVAs, t-tests etc.).
Computer literacy enabling professional presentation of scientific data.
Strongly Desired:
Experience with mammalian tissue culture, including culturing cancer cell lines.
Knowledge of cell biology, genetics and epigenetics at a level expected of a new graduate in health and medical science.
Experience using molecular techniques such as cloning.
Experience with protein and RNA analyses.
Experience with, or knowledge of, CRISPR gene editing techniques.
Need more information? Contact...
Professor Deborah Marsh
Deborah.Marsh@uts.edu.au
Other information
This project is part of a larger initiative funded by a NHMRC Ideas grant - "An Achilles’ heel of ovarian cancer: targeting ARID1A mutant tumours", Marsh and Bowden.
