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Sensing local biomolecular environments with coherent optical nanoscopy

   Cardiff School of Biosciences

About the Project

The development of novel imaging tools and technologies, including super-resolution optical microscopy, has revolutionised our understanding of biology. Combining light microscopy with chemical sensing at the nanoscale in living cells holds the promise to unravel processes presently not accessible with existing techniques. For example, lipid nanodomains (rafts) are thought to have a key role in the way cytosolic membranes work in signalling and other important functions, and have attracted much attention in basic biology and disease research [1]. Although many experiments indicate their existence, lipid rafts remain controversial owing to their small size and the lack of suitable detection techniques in living cells. A related example is endocytosis, the process by which membrane lipids, proteins and extracellular content become internalised into the cell. There are several endocytic routes into the cell, each with a distinct protein machinery, cargos, and internalisation mechanisms [2]. Their characterization is crucial, beyond fundamental biology, for the design of drug delivery and therapeutic strategies. A combination of light microscopy with chemical sensing at the nanoscale would allow us to directly observe membrane lipid nanodomains in living cells and to define the localised biomolecular environment at single endocytic events occurring at the cell surface.

The main aim of this project is to demonstrate and quantify the applicability of novel optical microscopy techniques beyond state-of-the-art for local biosensing of biomolecules directly within living cells. Specifically, the aim is to exploit a unique combination of coherent anti-Stokes Raman scattering (CARS) [3] microscopy of endogenous biomolecules and Four-Wave Mixing (FWM) imaging of metallic nanoparticles [4]. The local field enhancement of CARS in the vicinity of a plasmonic nanoparticle will enable bio-sensing while the nanoparticle position is located with precision at the nanoscale by FWM [5]. A unique home-built CARS/FWM microscope is available in the supervisor’s laboratory [3-5], therefore the main emphasis of this project will be to push its applicability for sensing directly in living cells.

Research Environment: You will be exposed to a vibrant multi-disciplinary environment at the physics/life science interface. You will join a well-funded academic team, with an outstanding track record of student supervision and publication output. The supervisory team offers a unique combination of expertise, with strong track records in developing novel optical microscopy techniques applied to life sciences (see e.g. [3-5]). You will be immersed in a collaborative environment with expertise in the biology of lipid membranes, endocytosis and intracellular trafficking. 

Training and Development Opportunities: You will be trained in a variety of relevant techniques including advanced optical microscopy methods and mammalian cell culture. You will develop the transferable skills of data analysis, communication and dissemination. The resulting skillset will boost your future employability both in academia and in industry. The supervisory team has strong links with companies, including microscope manufactures and image analysis software developers. Within this studentship, opportunities for visits/internships at these companies will arise. Global mobility opportunities will include visiting collaborating partner groups overseas, and participation to national/international conferences. The project will generate new knowledge and data that will be published in high quality journals. 

It is ideal that an applicant has an A-level in maths and physics (or equivalent).



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