Molecular mapping and quantification of cell-drug interaction by Raman microscopyProf Ioan Notingher & Penny Gowland
The design of novel drugs requires a detailed understanding on the way the drugs interact with the cells (both healthy and diseased) in the body. While the ultimate aim is to understand such interaction in-vivo, the early stages of drug testing is carried out in-vitro on 2- and 3-dimensional cell cultures. The drugs are designed to interact with specific molecules in the cells, and may induce spatial and temporal alterations to the cells. Understanding these interactions and the require fast imaging techniques that can measure time-dependent molecular changes in cells with high spatial resolution, and ideally without using external labels.
Raman spectroscopy is a technique that is based on Raman scattering of light, a phenomenon in which photons incident on a sample are inelastically scattered after interacting with vibrating molecules within the sample. This scattering process is highly specific to molecules. Since no external labels are used, the technique allows us to follow molecular changes in individual light cells. By using laser for the excitation of the Raman scattering, high-resolution molecular images can be obtained (Figure 1). More recently, this technique has been used for a broad range of biomedical applications, including cell imaging, disease diagnosis and drug discovery.
Project Outline and Goals
The main aim of this project is to develop new techniques based on Raman micro-spectroscopy to understand the time- and spatially-dependent molecular changes in live cells interacting with drugs. The project is based on a collaboration with GSK and will include a range of drugs and cell types of high relevance to the industrial partner. The focus of the project is to develop new imaging techniques and associated mathematical models that would allow us to understand the interactions at a molecular level. While Raman spectroscopy will be the main technique used, the project will included complementary techniques, such as mass spectrometry, confocal fluorescence microscopy and atomic force microscopy.
The student will be based in Nottingham in the Biophotonics Group and will interact regularly with the scientists at GSK. In addition, the student will visit and work at GSK in the mass-spectrometry imaging department for a few weeks, in the second part of the project.
 Dustin Shipp, Faris Sinjab, Ioan Notingher, “Raman spectroscopy: Techniques and applications in the life sciences”, Advances in Optics and Photonics, 2017 9(2), pp 315-428
 Adrian Ghita, Flavius C Pascut, M Mather, V Sottile, I Notingher, “Cytoplasmic RNA in undifferentiated neural stem cells: a potential label-free Raman spectral marker for assessing the undifferentiated status” Analytical Chemistry 2012, 84 (7), pp 3155–3162
PhD position starting September 2017, University of Nottingham, part of the joint Oxford-Nottingham EPSRC and MRC Centre for Doctoral Training in Biomedical Imaging (ONBI). This is a 4-year doctoral programme, involving intensive training across the breadth of biomedical imaging in the first year, followed by a focused thesis project for the remaining 3 years. The candidates should have a 1st or 2:1 degree in physics, chemistry, or biomedical engineering.
For further information, please contact Ioan Notingher or Penny Gowland
Compact Semiconductor Optical Components for Thermal Rubidium and Cold Potassium Atomic SensorsSupervisors: Dr Jessica Maclean and Dr Chris Mellor
This PhD project is aimed at developing photonic components adapted for specific quantum sensor systems. Photonic devices based on semiconductor waveguides will be designed and nanofabricated for use in the optical magnetometry sensors using atomic sources of thermal Rubidium atoms (wavelength 780 nm) in magneto-encepalography measurements and for optical switches necessary for a compact Bose-Einstein Condensate microscope based on cold atoms of Potassium (wavelength either 767 nm or 770 nm).
The PhD student will develop expertise in semiconductor materials characterisation and nanofabrication. Access to optical simulation software will allow the design of suitable epitaxial structures and multimode interference devices. Following successful optical insertion loss measurements of bare die, samples will be mounted in commercial opto-electronic packages. The devices will then be used in the atomic sensor and the magnetic detection performance compared with existing data.
The project involves the full transformation of semiconductor material to a systems component and provides sound expertise in future innovation in UK Quantum Technologies.
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