Combining a range of different imaging techniques to better understand the roles metals play in biology
Microscopes in various forms have helped identify disease-causing bacteria, miniaturize microprocessors and engineer superior metal alloys. However, in biology some things remain very difficult to see even at the highest levels of magnification. Metal ions (e.g. calcium, manganese, iron, etc) are essential for living cells to develop and function but can’t be seen with normal light. Nearly a third of all proteins in an organism (including bacteria, worms and humans) require a metal partner, or co-factor, to function correctly. These co-factors often help move electrons around for essential chemical reactions and help proteins to adopt a correct structure. Tissues and organs are also comprised of lighter elements such as sulfur, chlorine and potassium, not to mention the building blocks of organic molecules, carbon, nitrogen and oxygen. Being able to see metals ions would greatly help our understanding of the roles that metal ions play in important and fundamental biology. Knowing where and how much of these elements are located in organs and cells will help us better understand their role in health and disease.
In this study we used an intensely bright source of x-rays (at the Australian Synchrotron) to make atoms fluoresce (shine), giving us a finely detailed map in a simple microscopic roundworm, called Caenorhabditis elegans. This work involved collaboration across several disciplines of science, including biology, chemistry and physics. We were able to see elements, from relatively common phosphorous found in nearly all tissues to strontium, a rare element that in vertebrates (animals with back bones) is often incorporated in place of calcium in bones. The image resolution of the elemental maps produced was very fine, less than one-thousandth of a millimeter. This allowed us to compare our images against a centuries old technique for imaging iron. Perls’ staining, also called Prussian blue, stains iron on biopsy specimens. Perls’ staining, named after its inventor Max Perls (1843-1881, a pathologist from Giessen, Germany), involves a series of chemical reactions and has been a true workhorse for biology and medicine for more than a century. However, this technique only works for iron. Other chemical stains, often using toxic chemicals, are required for different metals, and no single stain can detect as many elements as an x-ray approach.
Equipped with these maps we are now ready to begin new kinds of research to explore what changes in biological metals occur at the very early stages of development through to the gradual process of ageing. We have previously seen that normal ageing in these nematodes is associated with dramatic changes in iron; a process that mirrors changes in the ageing human brain. This change in brain iron is thought to be a significant contributor to several age-related neurodegenerative diseases like Parkinson’s disease. We believe that the elemental imaging approach described in this study will be used to help us understand the role biological metals play in development, life and death.
Gawain McColl, PhD MRSC
The Florey Institute of Neuroscience and Mental Health
University of Melbourne
High-resolution complementary chemical imaging of bio-elements in Caenorhabditis elegans.
Hare DJ, Jones MWM, Wimmer VC, Jenkins NL, de Jonge MD, Bush AI, McColl G
Metallomics. 2015 Nov 16
|Post-prandial excretion of calcium is a risk factor… Calcium stones are caused by the precipitation of calcium-oxalate and/or calcium-phosphate on the surface of a kidney papilla. High urinary concentration of lithogenic ions, calcium and oxalate or phosphate, and…|
|Getting metals into mitochondria Scientists consider mitochondria, an organelle within cells, as a power plant. But mitochondria are also a site for metallurgy. There iron enters heme, the compound that binds oxygen in hemoglobin…|
|Mimicking enzymes using artificial proteins Critical to life on earth is the ability of proteins called enzymes to catalyze a wide range of chemical reactions, such as producing essential molecules by breaking down food in…|
|The mind and mouth of a predatory worm Nematodes (roundworms) are some of the most abundant and successful animals on the planet and are found in nearly every environment capable of supporting life. In order to exploit these…|
|Constructing a Google-Earth-like functional brain atlas Brain, the final frontier. These are the voyages of the brain cartographers. Their continuing mission: To explore strange new maps, to seek out new areas and new functions, to BOLD-ly…|
|Cellular stress and AMPK activators including… The neural mechanisms that give rise to human consciousness have been described as one of the greatest and most profound mysteries in all of modern medicine. The use of general…|