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Interrogating the impact of therapy on extracellular matrix remodelling during breast cancer progression


Project Description

Breast cancer is one of the most abundant cancer types and leading causes of cancer-related deaths in women worldwide. Approximately 20% of diagnosed patients develop metastasis, which is correlated with very poor prognosis and only limited treatment options due to drug resistance. It is now acknowledged that the tumour microenvironment at the primary and secondary tumour site play an important role in tumour progression (Kalluri, 2016, Obenauf et al. 2015). Thus, a better understanding of the often permissive crosstalk between the tumour and stroma is vital to fully comprehend drug resistance and to develop novel treatment strategies.

Our laboratory is particularly interested in metastatic tumour niches, and the interaction of tumour cells with the microenvironment, such as fibroblasts and immune cells, but also the extracellular matrix (ECM). Cancer-associated fibroblasts (CAFs) play a crucial role in remodelling the ECM and dysregulation of its composition, structure, stiffness and abundance can further contribute to tumour progression.

The overall goal of this project is to identify novel strategies to target the tumour stroma by combining in vitro 2D and 3D co-culture techniques (such as spheroid assays, hydrogels and ECM scaffolds) with in vivo and ex vivo models. The project will initially focus on the development of a 3D in vitro ECM model based on fibroblast-derived matrices to study the behaviour of CAFs under normal and stress situations, such as exposure to hypoxia, therapy or therapy-induced secretomes. We will further interrogate the role of cell to ECM interactions during cancer progression and during treatment by assessing the behaviour of human and mouse mammary cancer models (with different potential to metastasize) in the established models. In vivo metastasis models (Jungwirth et al., 2018) and bioinformatic analyses of clinical datasets will be used in addition.

The PhD student will be supported by a cross-disciplinary team with expertise in cancer biology, drug discovery and bio-engineering and will gain hands-on experience in advanced 3D cell culture and imaging techniques, molecular biology assays and in vivo mouse models.

If you are motivated and passionate about cancer research, interested in a broad range of methods and want to work on a medically relevant topic, you should apply. A BSc Honours/MSc or equivalent in biological sciences (e.g. Molecular Biology, Pharmacology, Biochemistry or related field) and previous laboratory experience (e.g. undergraduate placement) are essential.

For more information contact Dr Ute Jungwirth

Applications –

Formal applications should be made via the University of Bath’s online application form:
https://samis.bath.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RDUPA-FP01&code2=0013

Please ensure that you quote the supervisor’s name and project title in the ‘Your research interests’ section.

More information about applying for a PhD at Bath may be found here:
http://www.bath.ac.uk/guides/how-to-apply-for-doctoral-study/

Anticipated start date: 30 September 2019.

Funding Notes

Candidates may be considered for a University Research Studentship which will cover UK/EU tuition fees, a training support fee of £1,000 per annum and a tax-free maintenance allowance at the UKRI Doctoral Stipend rate (£14,777 in 2018-19) for a period of up to 3.5 years.

References

Kalluri R. (2016) The biology and function of fibroblasts in cancer. Nat Rev Cancer

Obenauf et al. (2015) Surviving at a Distance: Organ-Specific Metastasis. Trends Cancer

Jungwirth et al. (2018) Generation and characterisation of two D2A1 mammary cancer sublines to model spontaneous and experimental metastasis in a syngeneic BALB/c host. Dis Model Mech.

How good is research at University of Bath in Allied Health Professions, Dentistry, Nursing and Pharmacy?

FTE Category A staff submitted: 54.20

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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