Development and Characterization of Hydrogel-Based Model(s) for Pancreatic Cancer

About the Project

Pancreatic Ductal Adenocarcinoma (PDAC), which develops from cells lining pancreas ducts, represents 95% of all pancreatic cancer cases. In the UK alone, PDAC is the 11th most common cancer with ~10,000 new cases diagnosed every year. Despite advances in PDAC therapies, the increased and chaotic deposition of extracellular matrix (ECM) proteins around the tumour results in a physical barrier called the desmoplastic stroma. This stroma, renders PDAC chemotherapies ineffective leading to abysmal life-expectancy with only 7% surviving the first five years. PDAC death rates are constantly on the rise, and it is projected to become the second most lethal cancer by 2030. Therefore, there is an urgent need to develop novel therapeutics that can target desmoplasia or penetrate through the desmoplastic stroma to target cancer cells. This is an interdisciplinary project combining molecular biology and materials science to develop 3D models mimicking PDAC desmoplasia and enabling research into drugs targeting PDAC.

To achieve this, our overarching aim is to create biomimetic hydrogel-based model(s) composed of natural proteins to replicate pancreatic desmoplasia. To ensure that these models accurately represent the biological and physiochemical aspects of PDAC and its ECM, in vitro assays measuring viability and function of mono- and co-culture of cells will be used and will be compared to in vivo studies. Once established, these models will be used to assess novel or FDA approved drugs in their free form or as encapsulated in nanoparticles using in vitro and in vivo methods.

As part of this project, the student(s) are expected to a. generate and characterise physiochemical (eg. rheometry, SEM, and FTIR) and biological properties (eg. viability, proliferation) of these hydrogels for their ability to mimic PDAC and its ECM, b. generate and characterise (eg DLS, TEM, HPLC) nanoparticles loaded with various drugs, and c. measure the effects of free and encapsulated drugs on PDAC and its ECM using various in vitro (viability and proliferation assays, apoptosis, cell cycle) and in vivo approaches.

The PhD candidates will be closely supervised by both Dr Tapeinos and Dr Latif labs to ensure timely delivery of this project. This project is designed for four years (including write up period) and candidates who have scholarships secured for four years are invited to apply.

Questions about this projects should be directed to Christos.Tapeinos@manchester.ac.uk and Ayse.Latif@manchester.ac.uk.

Training/techniques to be provided

Candidates will be trained in various techniques provided by both supervisors. Through this project the student will gain interdisciplinary skills in molecular biology (training by Latif lab) and material sciences (training by Tapeinos lab). Where necessary training will be provided by staff at University core-facilities. Through this PhD project, the student will gain skills in mammalian cell (mono- and co-) culture, histological analysis of proposed models/human tumour samples, in vivo model development, methods that can be used for development and characterisation of hydrogels (rheometry, scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR)) and nanoparticles (dynamic light scattering (DLS) and transmission electron microscopy (TEM)) and several other functional assays required assessing effectiveness of free and encapsulated drugs (MTT, apoptosis assays, and proliferation assays; high-performance liquid chromatography (HPLC) and UV-Vis spectroscopy).

Entry requirements

Applicants are expected to hold (or about to obtain) a minimum upper second class undergraduate honours degree (or equivalent) in pharmacy, pharmaceutical sciences, biomedical engineering, (bio)medical sciences, biology or any other related subject. Candidates with a master’s degree in a related area/subject, and experience in pharmaceutical sciences, biomedical sciences, molecular biology or materials science 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 PhD Pharmacy and Pharmaceutical Sciences.

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