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Characterizing the heterogeneity of stem cells in the normal breast and breast tumours


Project Description

Tissue-restricted stem cells are crucial in supporting the development and maintenance of normal tissues. This is also true for tumours, as only a small population of tumour cells, which are known as cancer stem cells, have the unique stemness features and tumour-initiating capacity. The mammary gland is a highly regenerative organ that undergoes dramatic changes of tissue structure depending on the hormonal regulation during menstrual/oestrus cycle and the pregnancy-involution stages of its development. This dynamically changing tissue structure is dependent on the mammary epithelial stem cell (MaSC) function. Recent studies in the field and the ongoing work in our groups suggest that there is a high degree of heterogeneity within MaSC populations, as they can be found and reversibly transit between different states. However, the true identity of these different MaSC states and the molecular mechanisms regulating the switch between these stem cell states are still unknown. A similar heterogeneity of stem cell states is also present within the breast cancer stem cell (Br-CSC) population as shown in studies using cell lines and clinical samples. In this project, by using animal models we aim to better characterise the stem cell heterogeneity in normal breast and breast tumours in vivo and elucidate the molecular mechanisms regulating the transition between different stem cell states. The comparison of these molecular mechanisms regulating the stem cell heterogeneity in MaSCs versus Br-CSCs would result in identifying novel therapeutic approaches to target Br-CSCs, which are responsible for tumour progression, metastasis and therapy resistance.

Formal applications received till Feb 28th, 2019 will be considered for nominations to the prestigious President’s Doctoral Scholarship (PDS) Full Award. For details please check: https://www.bmh.manchester.ac.uk/study/research/financial-support/presidents-doctoral-scholar-awards/

Candidates are expected to hold (or be about to obtain) a minimum first class honours (or equivalent) in a related area / subject, with independent research in the lab or MSc degree. Candidates with academic scientific training in a relevant subject area e.g. molecular/cellular/cancer biology are encouraged to apply. Previous experience in working with animal models or primary cell cultures would be preferable. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor.”

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

http://www.breastcentre.manchester.ac.uk/Research-Groups/Ahmet-Ucar

http://www.breastcentre.manchester.ac.uk/Research-Groups/Keith-Brennan

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website)

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

• Olabi S., Ucar A., Brennan K., Streuli CH. Integrin-Rac signalling for mammary epithelial stem cell self-renewal. Breast Cancer Res. 2018
• Ucar A., Streuli CH. A role for β-3 integrins in linking breast development and cancer. Developmental Cell. 2014
• Acar A., Simoes BM., Clarke RB., Brennan K. A role for Notch signalling in breast cancer and endocrine resistance. Stem Cells Int. 2016.
• Moreno-Layseca P., Ucar A., Sun H., Wood A., Olabi S., Gilmore AP., Brennan K., Streuli CH. The requirement of integrins for breast epithelial proliferation. Eur J Biol, 2017-08-31
• Ucar A., Vafaizadeh V., Jarry H., Fiedler J., Klemmt PA., Thum T., Groner B., Chowdhury K. miR-212 and miR-132 are required for epithelial stromal interactions necessary for mouse mammary gland development. Nature Genetics. 2010.

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