Applications are invited for a 4 year PhD studentship within the laboratory of Dr Vito Mennella at the MRC Toxicology Unit, University of Cambridge. To commence October 2023.
Project Outline
The selection of lead compounds with limited toxicity for preclinical studies is paramount for cost-effective and timely drug development.
Despite the importance of airway targeting and inhalation in drug development, methodologies capable of predicting inhalation toxicity remain scarce. Moreover, the molecular mechanisms leading to airway toxicity remain largely unexplored. This is in part caused by the lack of effective tools required for mechanistic cell biology in primary cellular models recapitulating the airway cellular environment.
This project will examine compounds designed against specific molecular targets (and drugs without toxicity against identical targets) from the AZ library and beyond with known lung toxicities with the aim to better understand the mechanisms underpinning their negative impact. We will define how these toxicities manifest in healthy vs specific disease states using individualised patient air-liquid interface (ALI) organotypic and microphysiological systems (Liu et al. PMID 32188719).
By using a toolbox of cutting-edge methodologies in cell biology (e.g. Bio-ID proximity mapping, thermal proteomics, advance imaging technologies such as vEM and super-resolution microscopy) not yet widely applied in discovery toxicology in primary airway cellular models we will identify new outcome pathways of toxicity and develop methodologies that will better predict toxic effects in the airways at homeostasis and in specific airway disease states, with a focus in this project on PCD and COPD. The resulting information will inform discovery drug programs for mitigating away from these toxicities through chemical design. In turn, this has the transformative potential of improving the efficiency and safety of drug development and use.
The Medical Research Council (MRC) Toxicology Unit is a leading International Research Institute within the School of Biological Sciences, University of Cambridge. The Unit delivers mechanistic toxicology research, pursuing hypothesis-driven toxicological questions with a particular focus on the study of the causal links between exposure to endogenous and exogenous toxicants, molecular initiating events and adverse outcome pathways. The Unit's overall aims are to carry out pioneering research which leads to improved health and to train and mentor the next generation of toxicologists.
The Unit provides a supportive learning environment designed to meet the scientific and transferable skills required for an internationally competitive career. Our PhD Programme aims to train the scientific leaders of the future, giving them rewarding research projects with access to world-class facilities and expertise. Students receive toxicology-specific training in the Unit and through the ITTP | MRC Toxicology Unit (cam.ac.uk)
Application Process
Applicants should have or shortly expect to obtain a first or good upper second-class degree from a UK university, or an equivalent standard from an overseas university, in a relevant subject area. Strong analytical skills, in addition to creativity, curiosity, enthusiasm, and the ability to work in a team are essential.
You are strongly recommended to contact the project supervisor prior to submitting your formal application to find out more about the project and eligibility, Vito Mennella: [Email Address Removed]
Information regarding the application process can be found at: PhD Programme | MRC Toxicology Unit (cam.ac.uk)
All formal applications will need to be made through the University Application Portal: PhD in Biological Science (MRC Toxicology Unit) | Postgraduate Admissions (cam.ac.uk)
Your online application must include:
• A CV, including full details of all University course grades to date
• Contact details for two academic or professional referees
• A personal statement of interest
Closing date: Friday 31st March 2023 or once a suitable candidate is found. Early applications are recommended.
Please note that it may not be possible to respond to all enquiries regarding this studentship.
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