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Native Mass Spectrometry for the Structural Elucidation of Colourful Macromolecular Machines

Primary Supervisor: Dr Aneika Leney, School of Biosciences

Secondary supervisor: Andrew Lovering

PhD project title: Native Mass Spectrometry for the Structural Elucidation of Colourful Macromolecular Machines

University of Registration: University of Birmingham

Project outline:

Native mass spectrometry is an expanding structural biology tool to elucidate protein complexes and their functions within cells. Applications of this technology are greatly expanding in the pharmaceutical industry and in medical applications. However, the full capabilities of native mass spectrometry are yet to be revealed.

This PhD project will firstly involve the development of mass spectrometry approaches (specifically cross-linking mass spectrometry, top-down mass spectrometry and hydrogen deuterium exchange mass spectrometry) to characterise protein systems. The University of Birmingham offers state-of-the-art high resolution mass spectrometers that are pushing the boundaries within native mass spectrometry. The PhD student will be trained in operating this equipment, experience on which is currently highly sought within the pharmaceutical industry. In the final years, this gained knowledge with be applied to a variety of structural biological problems working alongside Andrew Lovering’s group.

Within the Leney group, one application of native mass spectrometry will focus on light harvesting complexes within algae. These macromolecular complexes contain sub-protein complexes that are some of the most colourful and fluorescent molecules known. They harvest light energy with extreme efficiency, which is something that would be excellent to replicate for use in light transmission to energy in solar panels. Native mass spectrometry is starting to reveal how these fascinating machines operate; an biological area in which great opportunities for discovery are arising. Working on this project will also involve training in SDS PAGE, UV-vis spectroscopy, fluorescence spectroscopy and X-ray crystallography.

Overall once completed, we envisage the PhD student will have an excellent all-around knowledge in structural biology and have the ability to apply native mass spectrometry to solve biological problems in any context, increasing greatly their opportunities for future employability. Excellent candidates will have a passion for structural biology and be eager to learn about mass spectrometry and how these instruments operate.

Key references:

  1. Leney A.C., Heck A.J.R. Native mass spectrometry: what is in the name? J. Am. Soc. Mass Spectrom. (2017) 28(1): 5-13.
  2. Tamara S., Hoeka M., Scheltema R.A., Leney A.C.*, Heck A.J.R.* A colorful pallet of B-phycoerythrin proteoforms exposed by a multimodal mass spectrometry approach. Chem. (2019) 5(5): 1302-1317.
  3. Recent Press Articles on use of Native Mass Spectrometry (Leney group):
  4. https://www.sciencealert.com/tiny-fluorescent-microalgae-could-inspire-the-next-generation-of-solar-panels 
  5. https://www.sciencetimes.com/articles/32230/20210712/protein-superglue-new-approach-pick-therapeutic-drugs-developed-healthy-body.htm

BBSRC Strategic Research Priority: Renewable Resources and Clean Growth: Bio-energy & Industrial Biotechnology: Understanding the Rules of Life: & Microbiology & Structural Biology

    Techniques that will be undertaken during the project:

    Mass spectrometry (including hydrogen deuterium exchange, crosslinking and native mass spectrometry), liquid chromatography, SDS PAGE, fluorescence and UV-vis spectroscopy, cation exchange chromatography, X-ray crystallography, use of various bioinformatics tools to handle large mass spectrometry datasets.

    Contact: Dr Aneika Leney, University of Birmingham