Prof Louise Donnelly, Prof Paul French
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
The role of macrophages is to clear and remove particles and pathogens and when this fails it may contribute to increased exacerbations and of progression chronic obstructive pulmonary disease (COPD). However, unlike macrophages in other parts of the body, under healthy homeostatic conditions, the lungs are not a serum-rich environment. This is important because most of the mechanisms into understanding the process of macrophage phagocytosis have focused upon opsonic uptake with little known about the mechanisms underlying non-opsonic phagocytosis. Phagocytosis is complex and requires engagement of cell surface receptors and activation of cytoskeletal rearrangements leading to particle engulfment and ultimate destruction inside the phagolysosome. This project will use human monocyte-derived macrophages to investigate the involvement and regulation of specific receptors and cytoskeletal proteins involved in the phagocytosis of different particles such as diesel particulates and pathogens including Haemophilus influenzae and Streptococcus pneumoniae. This will be investigated using flow cytometry and advanced automated fluorescence microscopy techniques in collaboration with the Photonics Group at Imperial College. Receptor trafficking following recognition of bacteria and particles will be examined using real-time microscopy to follow the fate of specific receptors. The role of the cytoskeleton will be investigated by transducing macrophages with lentiviral vectors that will express fluorescently labelled actin and tubulin to allow real time measurement of cytoskeletal rearrangements.
To this end, we will use confocal and high content microscopy approaches including the automated optically sectioned (spinning disc) microscopy platform that is available in the Photonics Group providing multi-colour fluorescence intensity and lifetime imaging of fixed and live cells with bespoke image segmentation and quantification capabilities including FRET readouts of protein interactions. We will be able to visualize specific receptor localisation together with cytoskeletal components and will implement 3-channel imaging, using fluorescence lifetime and wavelength to separate labels, and will also explore using FLIM/FRET to read out ROS biosensors (such as HyPer) correlated with bacterial uptake and receptor internalization and use Duolink assays to investigate protein interactions. We will also explore the novel application of super-resolved nanoscopy techniques including SIM and STORM to investigate changes in cytoskeleton and receptor localisation and ultimately identify novel targets for improving macrophage function.
This multi-faceted project will entail training in both biological assays as well as the application and further development of advanced fluorescence techniques and is an exceptional opportunity to take advantage of the cross-disciplinary research environment at Imperial College. As such, it represented an opportunity for physical scientists or life-scientists wishing to broaden their expertise.
How to apply
Initial applications should include a full CV, names, addresses and contact details of two academic referees, a personal statement (500 words max) and a covering letter.
Completed applications should be submitted to the DTP Team via email ([Email Address Removed]) by 5pm on the 10th February 2017.
Please note only shortlisted applicants will be contacted by the project supervisors.
Informal enquiries are welcomed and should be sent to Professor Louise Donnelly, [Email Address Removed].
Funding Notes
Applicants are expected to hold, or to be awarded a first class or a good upper second class BSc Degree, or an equivalent qualification, by October 2017.
The studentships are offered on a 1+3 basis (1 Year of Masters study followed by 3 years of PhD Research). In every case, the Masters Course will commence in October 2017 followed by the commencement of the PhD in October 2018. Only UK and EU students who meet the UK residency requirements are eligible to apply (minimum of three years of continuous residency in the UK immediately prior to the start of the PhD). Non-EU nationals are not eligible.
The studentships cover: (i) an annual tax-free stipend at the standard Research Council rate, (ii) contribution towards research costs, and (iii) tuition fees at the UK/EU rate.
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