PhD Research Studentships

Investigating the Disruption of Invading Breast Cancer Cells to the Regenerative Capacity of Bone Cells in a Tissue Engineered Tumour Microenvironment

Supervisor: Stefaan VERBRUGGEN
Apply by:29 January 2025
Start in:September (Semester 1)

Description

Metastasis in breast cancer reduces five-year survival rates in the UK from 99% to 15%[1]. One of the most common sites for tumour metastasis is bone, affecting approximately 70% of patients with over 24,000 in the UK alone[1]. Once metastasis to bone has occurred the median survival time is 1-4 years, indicating that metastasis is now the primary cause of death and suffering in breast cancer patients[2]. Therefore, a step change in our understanding of this complex process is required to elucidate new treatments and inform the next generation of anti-cancer therapies.

Bone cells begin as stem cells known as MSCs, which posess a significant degree of regenerative potential. In order to create bone, the MSCs differentiate (change) into osteoblasts, which can deposit a new mineral matrix and build bone tissue, before terminally differentiating into osteocytes, which act as the master regulators of bone growth.

While it is generally thought that most cells can only differentiate in one direction to become less stem cell-like and more specialised, recent evidence suggests that cancer cells can cause healthy cells to de-differentiate to become more like stem cells. [3] While this has been observed in breast cancer metastases in lung tissue, it has not yet been tested in metastatic tumours in bone. If this phenomenon was observed in bone cells then if could present a new therapeutic target to disrupt the growth of metastatic breast cancer and encourage growth of healthy bone.

Therefore this project will apply in vitro cell culture techniques to test for the first time the effect of breast cancer cells on the differentiation of MSCs, osteoblasts and osteocytes. Building on 3D tumour models developed in collaboration with Queen Mary's Centre for  Predictive in vitro Models and Barts Cancer Insitute [4,5], this project will unpick how breast cancer cells hijack healthy bone cells, potentially unveiling new targeted-therapies for late-stage breast cancer patients.

Aims:

The aims of this project are:

  1. Establish the effect of breast cancer cells on MSC and osteoblast cell activity (mineralisation, proliferation, differentiation)
  2. Characterise protein and gene expression in bone cells
  3. Determine whether changes activity are linked to the expression of particular genes, and whether differentiation or de-differentiation is occurring
  4. Unpick the underlying signalling mechanisms
  5. Develop new targetted treatments by blocking these signals in an orgna-on-a-chip model of breast cancer-induced bone metastases

Techniques:

In vitro Cell Culture, Molecular Assays, Western Blots, PCR analysis, RNAseq

References:

[1] Verbruggen, Journalof Bone Oncology, 2024;

[2] Coleman RE, Cancer Treat Rev, 2001, 27(3):165-76;

[3] Ombrato L, Nature, 2019, 572:603-608;

[4] Verbruggen et al., Cancers, 2021;

[5] Verbruggen et al.,  Advanced Science, 2024

Funding

Funded by: EPSRC
This EPSRC DTP studentship is fully funded and includes a 3.5 years stipend (currently set at the 2024/25 stipend rate of £21,237 pa) and 3 years fees at the home level.

Overseas applicants are encouraged to apply, but note that UKRI limit the proportion of international students appointed each year to 30% of the total.

Eligibility

  • The minimum requirement for this studentship opportunity is a good honours degree (minimum 2(i) honours or equivalent) or MSc/MRes in a relevant discipline.
  • If English is not your first language, you will require a valid English certificate equivalent to IELTS 6.5+ overall with a minimum score of minimum score of 6.0 in each of Writing, Listening, Reading and Speaking).
  • Candidates are expected to start in September (Semester 1).

Contact

For informal enquiries about this opportunity, please contact Stefaan VERBRUGGEN.

Apply

Start an application for this studentship and for entry onto the PhD Medical Engineering full-time programme (Semester 1 / September start):

Apply Now »

Please be sure to quote the reference "SEMS-PHD-653" to associate your application with this studentship opportunity.

Related website:https://stefaanverbruggen.com/
SEMS Research Centre:
Bioengineering
Keywords:Biotechnology, Cancer Biology, Cell Biology, Genetic Engineering, Bioengineering, Biomedical Engineering, Biomechanics, Medicine - Other, Pathology, Tissue Engineering