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Mechanism of interaction between phosphodiesterase type 5 inhibitors and selective oestrogen receptor modulators in human fibroblasts


Project Description

This project is supported by colleagues in MTRC

Fibrosis is the overproduction of extracellular matrix proteins which can impedes the function of organs. Fibrotic disease may be the cause of 42% of deaths in Western world. There is currently no efficacious and safe treatment options for fibrotic diseases. This has been attributed to the single-target approach typically used in therapeutic development in the last 5 decades. We have recently taken a “phenotypic screening approach” where a phenotype rather than single target is used for compound/drug screening. We have tested the approach with screened 1,954 approved drugs utilising primary human fibroblasts derived from fresh fibrotic clinical samples. This screening campaign delivered two hit classes: phosphodiesterase type 5 inhibitors (PDE5i) and selective oestrogen receptor modulators (SERMs). The two classes also showed a novel, previously unreported synergistic interaction.

The aim of this project will be to understand the mechanism of interaction between PDE5i and SERMs in human primary fibroblasts. The successful completion of the project is envisaged to decipher for the first time how the two intracellular pathways interact.

The successful applicant will be part of the Drug Discovery Research Group (https://aru.ac.uk/health-education-medicine-and-social-care/research/groups/drug-discovery-group) in the Medical Technology Research Centre. The focus for the Group is to discover and develop novel therapeutic approaches for fibrotic diseases and develop novel phenotypic screening assays for drug discovery. The successful applicant will be given training in aseptic cell culture, primary cell isolation from fresh human tissue, Western blotting, in-cell ELISA, ELISA, immunocytochemistry, immunohistochemistry, tissue sectioning using cryostat, PCR and cellular pharmacology.

To discuss the research project, please contact .

Candidate requirements


Applications are invited from UK/EU nationals only. Applicants are expected to hold, or about to obtain, a minimum upper second-class undergraduate degree (or equivalent) in a cognate discipline. A Masters degree in a relevant subject is desirable.

Applications


You can apply via our landing page http://www.anglia.ac.uk/studentships. We will review all applications after the submission deadline of 9 February. Applications missing the project reference number will be rejected as will applications for multiple studentships.

If you have any queries relating to the application process or the terms and conditions of the studentships, please contact Becky Kraszewski on 01245 684920, or email .

Documentation required


You will also need the following documents available electronically to upload them to the application portal (we can accept files in pdf, jpeg or Word format):

1) Certificates and transcripts from your Bachelor and Masters degrees, (if applicable)
2) Your personal statement explaining your suitability for the project
3) Passport and visa (if applicable)
4) English Language qualifications (if applicable)
5) Curriculum Vitae

Funding Notes

The successful applicant for this project will receive a Vice Chancellor’s studentship awards which covers Home/EU tuition fees and provides a UKRI equivalent minimum annual stipend for three years. The award is subject to the successful candidate meeting the studentship Terms and conditions.

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