Prof B Forbes, Dr I Mudway
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
Project Logistics
The studentship will be registered at King’s College London and is the ‘biology’ project (supervised by Prof Ben Forbes) to develop biological models for testing xenobiotic safety and absorption from the lungs. The project is designed to run in parallel with, and provide data for, a complementary ‘modelling’ project at University College London (supervised by Dr Rebecca Shipley). Both projects are sponsored as four-year iCASE studentships funded by the Biological and Biotechnology Research Council with Syngenta as the industrial partner.
The student will join the research group of Professor Ben Forbes in the Institute of Pharmaceutical Science at King’s College London. The research group has extensive experience and a wide range of activity in the design, manufacture and evaluation of inhaled pharmaceutical products. The second supervisor is Dr Ian Mudway, a lung biologist, working in the Environmental and Analytical Science Research Division. The supervisors have a history of collaboration, successful project supervision and joint publications.
Project Description
Currently, while conducting risk assessments, it is assumed that 100% of the pesticide particles and droplets that enter the respiratory tracts of operators, workers, bystanders and residents are absorbed into systemic circulation. For high crop, greenhouse and aerial uses, where inhalation exposures can contribute significantly to the overall exposure, refining the assumption of 100% absorption across the respiratory epithelium may represent an opportunity to use new science to develop/maintain our ability to register and sell competitive products and minimize use of mitigation measures (such as respiratory protection and closed cab tractors).
Computational fluid dynamics models (CFD models) have been developed that can predict the region of the respiratory tract where particles would deposit as a function of their sizes. But we do not understand the fate of these deposits well enough, including the extent to which they are metabolized, transported by the mucociliary escalator or absorbed in situ.
This project’s goal is to increase our understanding of inhalation absorption by marrying modeling and experimental efforts. For this effect, relevant regions of the respiratory tract will be selected as the more relevant for OPEX exposures based on the outputs of the existing CFD models. The effectiveness of the key clearance mechanisms in these selected regions as well as the level of in situ absorption will be modeled mathematically. Parameters for the models as well as validation targets will be provided by the experimental side of this project.
An experimental program will be designed that compares the selected in vitro systems based on trans-epithelial permeation of test compounds and establishes a reliable reporter system of airway absorption. This reporter system will then be used to inform and validate the mathematical model of airway absorption. In addition to producing parameters for the models, we will endeavor to understand the difference in fate between particles, droplets and aerosols.
Experimental Approaches
The biology studentship will focus on the determination of the impact of different biological and physico-chemical parameters on the local toxicology and bioavailability of inhaled materials in the lung. The key parameters of interest which may impact bioavailability or local hazard are:
• Phase – solid particle, droplet, vapour
• Effects of clearance mechanisms
• Physico-chemical parameters (e.g. solubility)
It will also be important to characterise the robustness of any cellular reporter system. When the test system is ready and has been tested using well characterised active ingredients, (a range of Syngenta active ingredients will be provided for testing).
This project description is not prescriptive and it is anticipated that the student will contribute increasingly to shape the strategic approach and experimental design as the project develops.
How to Apply
1) submit an application for a Postgraduate Research Degree to King’s College London (https://apply.kcl.ac.uk/),
AND
2) email your CV to [Email Address Removed].
Funding Notes
This studentship is a four Year iCASE award by BBSRC with Syngenta as the industrial partner
The project is fully funded for UK students or project funded (i.e. except stipend) for EU students
http://www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/
Candidates should have a first or upper second class degree in biomedical, health or life sciences. Essential attributes include independence, scientific curiosity and problem solving skills.
References
Kumar A, Bicer EM, Pfeffer P, Monopoli M, Dawson KA, Eriksson J, Edwards K, Lynham S, Arno M, Behndig AF, Blomberg A, Somers G, Hassall D, Dailay LA, Forbes B, Mudway I. Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid. Nanomedicine: Nanotechnology, Biology, and Medicine 12: 1033-1043 (2016)
Kumar A, Dailey LA, Swedrowska M, Siow R, Mann G, Arno M, Vizcay-Barrena G, Mudway I, Forbes B. Quantifying the magnitude of the oxygen artefact inherent in culturing airway cells under atmospheric oxygen versus physiologic levels FEBS Letters 590: 258-269 (2016)
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