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University College Dublin
University College Dublin
University College Dublin, Ireland
Nanoparticles are increasingly being used as therapeutic delivery vehicles, with more than 40 nanomedicines approved for clinical use. A critical aspect of their further development is gaining a greater understanding of their mechanisms of cellular internalisation and their subcellular distribution, as this knowledge will aid their efficacy for drug delivery. Currently, combinations of transmission electron microscopy (TEM) and fluorescence microscopy are used to assess their localisation in cells, but these methods are limited by their long preparation times, and the inconsistent imaging ability and fluorescent labelling of certain nanomaterial types. Soft X-ray tomography (SXT) will be evaluated as an alternative or complementary method to systematically assess and quantify nanoparticle uptake and distribution in cells, using nanomaterials derived from polymers, silica, metals, carbon and PLGA.
This project will utilise a wide range of animal cell culture systems, including monolayer (2D) cultures of cells representing various tissues and organs, as well as small spheroid (3D) models representing mini-tumours. The student will develop expertise in animal cell culture as well as how to manipulate these cells for imaging purposes, including transfection and immunostaining.
The student will also learn critical techniques in characterisation and use of nanoparticles made of various materials. These nanoparticles will be used in cell-based assays, and a wide range of biological imaging techniques (fluorescence light microscopy, confocal microscopy, high-content screening microscopy, electron microscopy, FIB-SEM microscopy) employed, and their performance compared to that of SXT microscopy. The student will also develop expertise in quantitative analysis across these imaging modalities such that they are able to precisely define the mechanics of nanoparticle uptake and distribution in the cellular models, as well as provide a systematic evaluation of the strengths and weaknesses of the various imaging techniques.
Quantitative analysis of nanoparticle uptake into cellular models (2D and 3D)
Nanoparticle types include polymers, lipids, PLGA, carbon, novel materials
Assessment of NP distribution in cells is at subcellular scale
Explore capacity of SXT imaging to evaluate NP distribution in cells
Image description: The images show a selection of cell types and models used for advanced fluorescence imaging applications to study nanoparticle uptake. a) various spheroid models stained with fluorescent markers; b) characterisation of polymeric nanoparticle uptake into a spheroid at subcellular resolution and showing the distribution of the nanoparticles (NPs) with respect to the lysosomes.
Role/Focus of PhD:
The student will be integrated within the UCD Cell Screening Lab (www.ucd.ie/hcs), a well-established and highly interdisciplinary team in UCD that studies the cell biology of a number of human diseases as well as drug delivery routes into cells. The successful candidate will be expected to fully participate the life of the lab and develop their own expertise in a wide range of advanced imaging techniques relevant to the project. The student will also support the wider function of the lab, which frequently hosts visiting researchers and students. The student will also be expected to produce high-quality publications during the course of their research.
Application Deadline: 18th August 2023 (Closed)