New synthetic nanoparticle probes that diagnose the microenvironment of the ageing tissue using mass spectrometry and fluorescence imaging
Prof Michael Hannon
Prof Z Pikramenou
Prof H J Cooper
Prof P G M Murray
Applications accepted all year round
Funded PhD Project (European/UK Students Only)
Skills & Training: This project is an exciting interdisciplinary research project drawing on the skills and knowledge of supervisors across the University and the University Hospital with skills in synthetic chemistry and nanoparticle design, molecular pathology of cancer, mass spectrometry, computational data and image analysis and clinical tissue pathology. You will develop skills in synthesizing and characterizing nanoparticles and fluorescent supramolecular compounds, handling and treating cells and tissues, mass spectrometries including mass spectrometry imaging, fluorescence imaging microscopies, electron microscopies, computational approaches to image and data analysis, and an understanding of the clinical needs and requirements, and the potential and opportunities for diagnosis of disease in a hospital pathology laboratories. To support you in gaining these skills, you will undertake a range of interdisciplinary taught and practical skills modules at the outset of the PhD.
Background: The inflammatory microenvironment is a critical driver in the development of chronic illnesses in ageing patients, with cancer being a prominent example. Age-associated exponential increases in the incidence of chronic diseases are well documented and there is growing evidence that the ageing microenvironment is more able to promote the development of these chronic illnesses. These effects are mediated through a variety of different mechanisms that depend upon functional changes that can be recognized by alterations in cell phenotype and biochemistry. In essence, the progress of a disease depends not only on the presence of individual cells, but on what cells are around them and what messages these cells communicate to each other.
Current clinical pathology techniques administer labeled antibodies to the tissue for recognition of a single marker on single cells. However, ageing cells show complex phenotypes and their proper characterization requires (i) the use of multiple markers and (ii) the ability to detect different adjacent cells. This would bring a breakthrough in our ability to detect and phenotype disease promoting inflammatory cells within tissues, providing an opportunity to unravel the contribution of ageing to disease progression. Nanoparticles are attractive in this context as they offer the advantage of a surface for attachment of antibodies and the availability of multidetection techniques for imaging in tissues.
Aims To create new labels that can (i) detect and label single cells and (ii) detect several markers on adjacent cells in a tissue. We will develop methodologies to label gold nanoparticles with different antibodies. We will explore their ability to detect single and adjacent cells both in tissue models and real tissues and optimize the nanoparticle structure and composition to maximize detection sensitivity and accuracy (minimizing off target response). We will then use the labels to probe the biochemistry of single cells using mass spectrometry.
Scientific outcomes The project will develop new, labelled nanoparticles and use them to phenotype tissue microenvironments and investigate how this impacts on inflammation and disease. We envisage publications arising from the nanoparticle design and preparation (nano-chemistry journals), the use of the nanoparticles to recognise adjacent cell areas in a tissue (interdisciplinary chemistry-biomedicine journals), and in the understanding impact of ageing on the phenotype and biochemistry of inflammatory cells afforded by the nanoparticles (biological/biomedical journals). The computational aspects will be inherent to the studies and thus likely incorporated within the interdisciplinary papers rather than standing alone.
This PhD project sits within the EPSRC Centre for Doctoral Training in Physical Sciences for Health (Sci-Phy-4-Health) & encompasses a 4 year Integrated PhD programme. Each year the CDT is able to offer a fully funded scholarship from EPSRC to UK students (tax free stipend £14,553 for entrance in 2017/2018).
EU students are eligible for awards of tuition fees only but may also be eligible for stipend funding if they have studied or worked in the UK for at least 3 continuous years immediately prior to course entry. Candidates are advised to check the EPSRC website for eligibility details.
S. Osborne; Z. Pikramenou; Faraday Discuss (2015) 185, 219;
D. J. Lewis; V. Dore; N. J. Rogers; T. Mole; G. Nash; P. Angeli; Z. Pikramenou Langmuir (2013) 29, 14701
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FTE Category A staff submitted: 28.00
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