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  Communication of tumour cells with the blood-brain barrier


   Faculty of Biology, Medicine and Health

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  Dr Jeff Penny, Dr Constantinos Demonacos  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The blood-brain barrier forms the crucial interface between the systemic circulation and the privileged site of the central nervous system (CNS). The blood-brain barrier maintains CNS homeostasis and limits exposure of the CNS to both exogenous xenobiotics (e.g. dietary and environmental toxins, pollutants and carcinogens) and endogenous agents (e.g. hormones).

We have developed a robust, physiologically-relevant in vitro model of the blood-brain barrier which possesses key characteristics of the in vivo barrier including highly restrictive tight junctions, functionally active drug efflux transporters, and important nuclear receptors that regulate detoxification systems within the blood-brain barrier.

Tumours are found at many sites of the body, both in peripheral tissues and within the brain itself. This PhD project will study how tumour cells interact with the endothelial cells of the blood-brain barrier and investigate the potential of tumours cells to modulate the protective function of the blood-brain barrier in vitro.

Eligibility 

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant subject area. Applicants with experience in aseptic culture of mammalian cell lines or with an interest in cancer are encouraged to apply.

Before you Apply 

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.  

How to Apply 

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. On the online application form select the appropriate subject title - PhD Pharmacy and Pharmaceutical Sciences.

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 https://www.bmh.manchester.ac.uk/study/research/international-phd/

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]  

Equality, Diversity and Inclusion  

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/  

Biological Sciences (4) Medicine (26)

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 https://www.bmh.manchester.ac.uk/study/research/fees/

References

Shubbar M, Therapeutic drugs modulate ATP-Binding Cassette transporter-mediated transport of Aβ(1-42) in brain microvascular endothelial cells. Eur. J. Pharmacol., 2020.
Shubbar M, Effect of amyloid beta on ATP-binding cassette transporter expression and activity in porcine brain microvascular endothelial cells. Biochim. Biophys. Acta Gen Subj., 2018.
Torres-Vergara P, Pro-inflammatory and anti-inflammatory compounds exert similar effects on P-glycoprotein in blood-brain barrier endothelial cells. J. Pharm. Pharmacol., 2018.
Bakker EY, Fujii M, Krstic-Demonacos M, Demonacos C* and Alhammad R. Protein Disulfide Isomerase A1 (PDIA1)-associated pathways in the development of stratified breast cancer therapies. International Journal of Oncology 60 (2022) 16 https://doi.org/10.3892/ijo.2022.5306.
Qattan M Y, Bakker E Y, Rajendran R, Chen D W C, Saha V, Liu J, Zeef L, Schwartz J-M, Mutti L, Demonacos C*, Krstic-Demonacos M. Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia. PLoS ONE 12(6) (2017) e0178606. https://doi.org/10.1371/journal.pone.0178606.