Investigating the mechanisms of biological calcification using cryo-electron microscopy and super-resolution microscopy

Supervisors: Fabio Nudelman, Colin Farquharson, Mathew Horrocks

Project Description:

The use of inorganic materials to produce mineralised tissues such as bone and teeth is a fundamental process in Nature. Organisms from all 5 kingdoms are well known to produce a wide range of mineralised structures that are optimally adapted for essential biological functions including mechanical support, protection and navigation. Among the many mineralising organisms found in nature, coccolithophores are one of the most interesting. These organisms are marine unicellular algae that produce scales of calcium carbonate crystals called coccoliths, that form an exoskeleton around the cells [1]. Each scale is made of nano-crystals of calcite assembled into a complex disk-like structure, constituting an astonishing example of the ability of organisms to precisely control the nucleation, growth and shape of nano-crystalline building blocks, and further orchestrate their assembly into complex structures [1]. Coccolithiophores are also fascinating in that the shape of the coccoliths produced are genus-specific, which demonstrates that the mineral patterns they produce are genetically controlled. Finally, biomineralisation by coccolithophores are of high importance to the environment and Earth’s biogeochemical cycle. They produce ca. 1026 coccoliths/year and are responsible for ca. 50% of deep sea carbon burial, forming the largest geological sink of carbon from the ocean/atmosphere reservoir [2]. The significance of coccolithophore biomineralisation to our environment, coupled with their abundance in our oceans, highlight the need to understand the mechanism of calcification in these organisms and how that will respond to anthropogenic change, including ocean acidification. To date, however, we still don’t know how coccolithophores produce such distinctive and sophisticated mineral patterns.

The goals of this research are to elucidate the mechanisms by which coccolithophores control the nucleation and the assembly of nano-crystals of calcite to generate highly complex scales. For this, we will focus on determining the structure and surface chemistry of the base plates – the substrates that promote the nucleation of calcite crystals and determine their organisation into a complex scale [3]. We will use a combination of cryo-transmission electron microscopy and tomography [4] and super-resolution microscopy to identify the key features that are responsible for promoting the nucleation of nano-crystals of calcium carbonate and their assembly, ultimately controlling the overall coccolith shape.

Training: The supervisory team of this project merges expertise in chemistry/biomineralisation (FN), cellular biology/biomineralisation (CF) and super-resolution microscopy (MH), which, in addition to training in scientific research and analytical methods, will ensure the acquisition of skills in several areas, including electron microscopy and crystallography, cellular biology techniques and super-resolution microscopy.

1. Young. J. R. et al. Coccolith ultrastructure and biomineralisation. J. Struct. Biol. 126, 195 (1999).

2. Monteiro, F. M. et al. Why marine phytoplankton calcify. Science Adv. 2, e1501822 (2016).

3. Gal, A. et al. Macromolecular recognition directs calcium ions to coccolith mineralization sites. Science 353, 590 (2016).

4. Nudelman, F. et al. The role of collagen in bone apatite formation in the presence of hydroxyapatite nucleation inhibitors. Nat. Mater. 9, 1004 (2010).

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