Microfluidic chip-based tumor-immune cancer models for biomarker discovery

Overview

In-vitro profiling of tumour-immune cell interactions in proximity can provide valuable insight into patient response to new combinatorial immunotherapies that are in the pipeline and currently being tested in clinical trials.  These in-vitro models allow for a more controlled and isolated environment and provide a methodical approach for generating quantifiable data characterizing the interactions between target and effector cells.  Traditionally executed in well-plates, tumour-immune models have been slowly moving towards a microfluidic chip-based approach for several reasons: better control over the design of the cellular interaction regions of interest, enhanced visualization capability, and focused analysis.  Recently, we have developed a microfluidic chip-based platform (OncoMiMIC) which mimics the tumor microenvironment (TME) and can compartmentalize and control interactions between different cell types commonly found in the TME.  The on-chip in-vitro response of patient-derived cell (PDC) tumor models to different types of cancer therapies can potentially be used to predict the actual patient response in the clinic, assuming the gene expression signatures (biomarkers) of the patients’ tumors are similar.  The baseline gene expression levels of PDCs before exposure to the therapy can be determined using RNA sequencing (transcriptomics).  The OncoMiMIC platform allows for recovery of cells after exposure to the therapy, and therefore, any changes in the tumor’s gene expression levels due to exposure to the therapy can also be measured.

This project is part of an ongoing collaboration between QUT and Genome Institute of Singapore. Successful candidates will have the opportunity to undertake up to a 2 year sponsored internship in Singapore.

Research activities

• Develop a patient-derived tumor spheroid seeding and on-chip co-culture protocol using the OncoMiMIC chip.
• Model the interactions between the tumor (target) cells and immune (effector) cells in an on-chip recapitulated tumor microenvironment.
• Perform upstream and downstream transcriptomic analysis of tumor samples and use bioinformatics to develop quantitative models for comparing differences between cell lines which are 'responsive' or 'non-responsive' to immune mediated cytotoxicity.

Outcomes

The proposed project aims to develop a proof-of-concept cancer biomarker discovery platform by using OncoMiMIC to co-culture on-chip patient-derived tumor organoids/spheroids (PDO/S) together with an appropriate allogeneic effector (immune) cell type (e.g. NK cells), in the presence or absence of other cell types (e.g. cancer associated fibroblasts, macrophages, endothelial cells) commonly found in the tumor microenvironment (TME).  The key genes responsible for differences in measured response between different cell lines can then be identified and studied using transcriptomics to propose potential mechanisms involved in determining future cancer patients’ (with similar gene signatures) potential response to immunotherapy.

Skills and experience

Candidates are expected to have obtained a First Class Honours (or equivalent) undergraduate degree in chemical/biomedical engineering, biological science or a related discipline. Preference will be given to candidates with prior experience with cell culture, in-vitro assays, microfluidics, principles of bioinformatics and transcriptomics, and microscopy. Postgraduate research scholarships will be available to top ranking applicants on a competitive basis.

Scholarships

You may be eligible to apply for a research scholarship.

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Keywords

• microfluidic device
• tumour-immune models

Contact

Contact the supervisor for more information.