Proteomics & Metabolomics Facility at Roslin Institute shows molecules in a new light

High-tech facility can support a wide range of studies of proteins in various tissues by providing detailed analysis of the proteins present. It's available to scientists throughout the University.

 

Our understanding of disease benefits enormously from insight into proteins. These large, complex molecules are at the heart of biological organisms, forming the building blocks of tissues, organs and systems, and are central to the functional processes that enable and sustain life.

Understanding their physical makeup and structure, their occurrence, and their interactions with other molecules is important to our knowledge of what constitutes healthy tissue and how disease affects it.

In a living organism, the types of proteins present can vary from cell to cell and at different times, posing challenges for characterising and understanding their functions.

The Roslin Institute's newly established laboratory facilities enable rapid and accurate analysis to identify protein molecules of interest in cells, tissues, or body fluids.

This means studies can be discovery-led rather than hypothesis-led – we don’t have to decide in advance what we expect to find in damaged tissue, for example, in a brain affected by Alzheimer’s disease, we can compare tissue from areas of the brain affected by disease against healthy tissue, to identify the nature of the proteins involved, as well as just seeing where the damage physically occurs.

Protein signatures

The facility's mass spectrometer, one of only two of its kind in the United Kingdom, uses a laser light that interacts with proteins in samples. It produces images that show the molecular fingerprint of a range of proteins and their position in situ at a high spatial resolution - down to 10 micrometres, or one-thousandth of a centimetre - equivalent to the size of a cell nucleus.

When a deeper understanding of sample composition is required, biological samples can be prepared and run through an instrument that can separate components of interest before their mass is analysed in the mass spectrometer.

The instrument can process up to 300 samples in a day, allowing researchers to quickly obtain a wealth of data on various proteins of interest.

Mass spectrometry provides an overall picture of all detectable proteins in a sample. This is in contrast to conventional analysis using microscopic imaging, where the proteins to be analysed must be determined prior to sample preparation.

Mass spectrometry imaging can also detect small molecular components of cells, such as products from metabolic processes, lipids, or even administered drugs. If individual components have the same mass, they can be distinguished by their shape.

The highly sensitive instruments are suitable for projects where only small amounts of valuable tissue are available, such as biopsy or post-mortem examinations. Direct Analysis in Real Time, or Dart, mass spectroscopy is also available in the proteomics laboratory.

We can support biomedical or clinical research by offering capabilities that exceed those available within individual groups. We’re actively seeking to develop new ways of applying the technologies to support research and expand the scope of the facility, and we’d be glad to hear from colleagues whose studies might benefit from novel use of the technologies.

This instrument, unique in an academic laboratory in Scotland, works with solid or liquid samples without the need for special preparation. It has many potential applications in forensics and was used in a study attempting to distinguish between bone tissue from wild and captive-bred big cats to aid anti-poaching efforts. In addition to these capabilities, researchers are commissioning an electron microscope that can work with 3-D samples. The device repeatedly slices and scans tissue blocks from samples to create a three-dimensional image at ultra-high resolution. This scanning electron microscope can be used with serial slices to study cell membranes, viral particles or connections in the brain, for example.

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