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Research projects

High-throughput imaging for cancer research applications

PhD project - Ruth Sims
Her project is: High throughput imaging for cancer research applications. In this project we have focused on applications that are severely limited by image acquisition times. In particular, in collaboration with CRUK:CI, we have identified higher throughput of imaging of large cleared tissue as pressing need.
Imaging large (10s of mm) cleared tissue can take 10-20 hours on a point scanning confocal microscope. Designing and constructing an upright light sheet microscope for automated imaging  has led to a 10 fold reduction in imaging times, with large intestinal adenocarcinomas being imaged in 90 minutes rather than 12 hours.
With design and construction of the microscope complete the next phase is to optimised the image acquisition software and analysis.

Super-resolution beyond the coverslip

PhD project - Sohaib Abdul Rehman

Super resolution beyond the coverslip

Resolution of a light microscope is fundamentally limited by the diffraction limit of light to around 200-300 nm, hindering the study of biological phenomenon below that scale. Localisation microscopy overcomes the diffraction limit by resolving molecules, within the diffraction limited region, in time as shown in Figure 1. Moreover, combining localisation microscopy with asymmetric point spread functions (PSFs) such as double helix and astigmatism (Figure 2) can provide information about axial position of emitters over 5-6 µm range, which significantly reduces the imaging time.

Since localization microscopy involves collecting weak signals from point emitters, refractive index mismatches within biological samples affects localization precision and accuracy by introducing various optical aberrations. I am working on characterisation of these aberrations under different imaging conditions and exploring techniques to image deep in thick samples by overcoming aberrations. Moreover, I am also interested in exploring localisation algorithms for 2D and 3D PSFs.

A) Inactive molecules, B) Stochastic activation of a sparse subset of molecules, C) Imaging, D) Localiation of molecules, E) Deactivation before the next iteration in (F). Black and yellow molecules indicate active and inactive molecules respectievely.

Multi-modal imaging for assessing chemical intervention in biological systems.

PhD project - Flaminia Kaluthantrige Don
The aim of this project is to explore new imaging techniques and protocols to maximise the information that can be gained from biological systems under chemical intervention. This project is run in collaboration with Meritxell Huch and GlaxoSmithKline through a BBSRC CASE studentship.
In a very early phase we are exploring the use of light sheet and 2-photon scanning microscopy for imaging organoids in timelapse imaging over several days.
Below: light sheet image of liver organoid labelled with the FUCCI system. FUCCI is a genetically encoded two color (red and green) indicator that allows tracking of the cell cycle stage