PHD Studentship - Investigating the Mechanistic Role of Extracellular Vesicles in Anti-cancer Drug Induced Cardiotoxicity

Anti-cancer drugs are known to inadvertently disrupt cellular dynamics in the heart, leading to structural and functional changes that ultimately can cause the heart to fail. Recent publications have suggested that extracellular vesicles (EVs) may play a role in this toxic mechanism (Yarana et al, 2022). Preliminary data collected by this research group demonstrated that EVs isolated from endothelial cells treated with the anti-cancer drug sunitinib malate led to a decrease in cell viability when introduced to healthy, untreated endothelial cells. In this project we plan to progress this work to better understand the role EVs play in this process. We aim to (i) characterise the content of EVs isolated from cardiac cells treated with an anti-cancer drug; (ii) investigate the effect these EVs have on other cardiac cell types and elucidate the mechanism; and (iii) determine whether this cardiotoxic mechanism can be reduced/reversed by modulating EV uptake and/or content. The results of this project may lead to the identification of a novel component of the cardiotoxic mechanism that could serve as a target for pharmacological intervention to reduce/reverse this toxicity. Further information: This three-year research studentship is funded by the Faculty of Science, Technology, Engineering and Mathematics (STEM) at The Open University and provides a stipend of £19,237 per year (2024/25 rate, indexed annually) and all academic fees are covered. The project is supervised by Dr Calum McMullen (Principal Investigator), Dr Katja Rietdorf and Dr Daniel Johnson (Co-Investigators). The student would be required to live in the UK and within commuting distance of The Open University in Milton Keynes.

Applicants will be expected to have a good undergraduate degree (upper second class or higher) in Pharmacology, Biomedical Science, Biology, Biochemistry, or a related area. Though previous experience in the following is not essential (all of the techniques required for this project can be learned), this project would be well-suited to candidates who:

• Are experienced in mammalian cell culture.
• Have experience in cell imaging/microscopy (wide-field or confocal fluorescence microscopy) and/or molecular biology techniques (electrophoresis, Western blotting, IHC/IF, flow cytometry etc).
• Have excellent communication skills, the ability to conduct scientific literature searches independently, and data analysis experience with proficiency in statistical software.
Most importantly, applicants should have a passion for science and a willingness to learn.

Unit : Faculty of Science, Technology, Engineering and Mathematics (STEM) Salary : Stipend: £19,237 per annum Please quote reference : PHD Studentship Investigating the Mechanistic Role of Extracellular Vesicles in Anti-cancer Drug Induced Cardiotoxicity Closing Date : 10 February, 2025 - 17:00 Investigating the Mechanistic Role of Extracellular Vesicles in Anti-cancer Drug Induced Cardiotoxicity Supervisory team: Dr Calum McMullen, Dr Katja Rietdorf and Dr Daniel Johnson (The Open University) Location: The School of Life, Health and Chemical Sciences (LHCS), The Open University, Milton Keynes. This project is part of a collaboration with an industry partner, Excellio Ltd. (Edinburgh, UK), and you will have the opportunity to complete a short placement (1 month) with Excellio to gain practical skills and industry experience. Duration & Funding: Three years and 3 months from 1st October 2025 Stipend: £19,237 per year (2024/25 rate, indexed annually)