Cells to Molecules: Structural EM at Newcastle University

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Light microscopes are limited in terms of the level of detail they can provide of cells and it is not possible to use them to look at the fine structure of the internal features of cells or molecules. Transmission Electron Microscopes (TEM) use high energy electrons rather than light to produce images and provide over 1000 times the level of detail possible with a light microscope. Using a TEM it is possible to look at the structures within cells to see how they form and even see the arrangement of atoms within proteins and protein machines. In the last twenty years, the technology behind TEM instruments and the cameras used to acquire images from them have undergone significant developments. One of the major drawbacks of imaging with a TEM is the limited contrast available from biological samples and the resulting impact of noise on the images. This makes our studies difficult as it is often hard to see the structures we are looking at clearly. Modern TEMs are equipped with cameras capable of taking images with very low noise and even capturing movies to allow very fine detail to be observed that would otherwise be lost. One major advance has been the preparation of samples at very low-temperatures, this allows cells and molecules to be viewed in a naturally hydrated state and minimises the spread of sample damage caused by the electrons from the microscope. This technique is known as cryo-EM and permits cells and proteins to be imaged with a level of detail at which it is possible to see the individual amino-acid components of proteins.Our research projects cover a wide range of subjects from understanding how the intestinal pathogen Clostridium difficile forms disinfectant resistant spores; to the production of DNA-based nanowires for use in electronics and conductive polymer materials. Other projects seek to understand how particular genes influence the formation of kidney tissues. We are also interested in how proteins called cyclin dependent kinases interact with their partner proteins to influence cell division and the production of RNA messages encoding proteins. This work has implications for the development of anti-cancer drugs.