Interview Professor Maggie Cusack
Back to the future…
Interview Professor Maggie Cusack
Back to the future
Her first degree was in cell biology and her PhD on protein biochemistry, but Professor Maggie Cusack Head of the School of Geographical and Earth Sciences at the University of Glasgow) has established herself as a pioneer in geoscience, applying her discoveries about living organisms to advance our understanding of the ancient past recorded in fossils – allowing access to a more accurate and reliable record of climate change. And now her work in biomineralisation has yet another strand, promising future advances in medicine and engineering by creating new materials inspired by the structure of shells, bones and corals...
The image of geologists chipping away at rocks looking for fossils may seem a far cry from biological experiments or electronic engineers using nano devices to simulate the behaviour of proteins, but Professor Maggie Cusack's work in biomineralisation provides the connection.
According to Cusack, studying a fossil to understand the ancient past requires an in-depth knowledge of how invertebrate shells grow and the environment in which the fossil formed many millions of years ago. This requires a multidisciplinary approach, taking advantage of the latest technological tools, including nanotechnology, advanced computing and innovative scanning techniques. Nowadays, collaboration may seem an obvious way to approach most problems in science. However, not so long ago most researchers tended to work in their own departments and were often unaware of the insights they may be able to gain by connecting with a disparate set of disciplines and what this could bring to the study of fossils – it simply was not part of the scientist’s basic training. In fact, says Cusack, the work of many scientists today has become so diverse that it now “defies classification.”
Recent advances in biology and geoscience, combined with a more collaborative approach to research, have revolutionised the way we study fossils and led to some remarkable advances in our understanding of what life was like on our planet hundreds of millions of years ago. These advances have also provided a much more detailed awareness of our recent history.
For example, when we study a fossilised shell to find out what it recorded about its long-lost environment – e.g. water temperature and ocean pH – the non-biologist’s approach would be to grind the fossil into a homogeneous powder and measure various properties in a bid to build up a picture of what life was like when the fossil was formed – i.e. how it laid down certain minerals during its life. Even if researchers used the latest technology to analyse the sample, the result would only provide an “average” or an approximate record contained in the fossil, and this could be highly misleading.
Cusack says we would get a much more accurate picture by applying our biological knowledge. For example, the ornate, often highly-specific design of many shells across our oceans is due not simply to the laying down of inorganic cements, but is “completely and exquisitely, controlled by biology,” and understanding this process (biomineralisation) leads to a huge “improvement in resolution” – the difference between a blurry, black and white image and full-colour, high-definition.
As a biologist, Cusack’s approach is to establish first how shells or corals grow while they are living, including the role of proteins – passing on instructions to determine the pattern of growth and their mineralogy – in the laying down of very precise nanostructures. This involves identifying which part of the organism – e.g. a brachiopod – tells the “true story” of how it developed its shell by analysing how it grows in real time, absorbing components such as magnesium and calcium and transforming them into the crystalline structures that form a shell. In this way, she is able to identify exactly which part of a fossilised shell contains the most accurate “historical” record. By using the latest techniques such as scanning electron microscopy (SEM), electron backscatter diffraction (EBSD) and mass spectrometry, she is able to extract this “hidden” information. In other words, she knows much more precisely where to look for evidence – and, importantly, how to interpret it when it is found.
One of the most important applications of this biological approach to analysing mineral records is the detailed picture it provides of climate change. In Cusack’s view, it's vitally important to establish the most accurate possible picture of climate change, because without these solid facts, debate can go in all sorts of misleading directions.
“Sometimes, scientists jump to conclusions,” says Cusack. “Things often happen in the wrong order, when big scientific announcements are published prematurely, before the fundamental checks are in place – not just collecting data but knowing how to analyse that data. We have to check and double-check every result.”
For example, using advanced techniques, such as the high energies provided by a synchrotron source, allows a more detailed analysis of the tomography of biomineral structures and the chemistry of the elements used as climate proxies. This provides scientists with a more accurate image of the environment in which the organism existed and essential knowledge of how it acts as an accurate recorder (or “proxy”) of past climate.
Cusack did her first degree in cell biology and her PhD on protein biochemistry, studying a sweet protein and identifying exactly what makes that particular protein taste sweet. This may seem a strange introduction to geoscience, but Cusack started gravitating in that direction by asking “big questions” about the behaviour of proteins in the process of biomineralisation. This desire to gain information about how proteins are involved in shell growth would have a significant bearing on her later study of fossils, and today she specialises in biomineralisation, the process by which living organisms produce highly organised minerals to harden or stiffen their tissues – e.g. silicates in algae, carbonates in invertebrates and phosphates in vertebrates, forming structural features such as shells in marine organisms and bones in mammals and birds.
The way that biominerals form shells and fossils also provides a very accurate embedded record, not only of the ocean’s temperature many eons ago, but also how acidic the oceans were at that time (which reflects the levels of atmospheric carbon dioxide at any given time). This is even more important at present, when there is a greater interest in investigations into ocean acidification. The method used to “travel back in time” is to take a sample which has already been dated, and analyse the ratio of components, e.g. magnesium and calcium. Alternatively, the ratio of the stable isotopes of oxygen and/or carbon contained in the sample can be measured with extreme precision by mass spectrometry. Both the changes in magnesium and calcium ratios and/or changes in isotopic ratios vary according to climatic conditions. These are the standard “proxies” or established standards used to gain information about past and present climate – e.g., when the ocean is warmer, more magnesium is present in the shell ultrastructure.
The important aspect of Cusack’s research is that she understands the biology behind the shell’s growth – how different layers of the shell structure are laid down at different times in its development and the fact that these characteristic climate proxies will vary significantly during different periods of shell development. This knowledge allows her to analyse the part of the fossil or shell in which these proxies are stable, providing a much more accurate record of climatic conditions.
Cusack explains: “Living systems exert exquisite control on biomineral formation, producing functional structures that are light and strong. There is, therefore, a drive to mimic and improve on biology’s approach and this requires that we understand the biological control of biomineralisation. Living systems control the structure, mineral type and polymorph of biominerals. In biology, minerals tend to be composites of vast numbers of nanogranules, with associated organic components, that are assembled to form structures that are effectively single crystals.”
Brachiopods are often used for gathering data, and fossilised examples are available which date back 550 million years. “They provide a fabulous record,” says Cusack, allowing us to look at “slices of time” which indicate changes in chemistry (i.e. the absorption of calcium carbonate) in chunks of time as finely grained as every two weeks, much as tree rings show the annual growth rate of trees, with rapid growth in good years and slow growth in bad years.
Cusack’s work not only has implications for our understanding of the planet millions of years ago, but could also help in the development of new synthetic materials for use in everything from medicine to engineering and construction. Working in collaboration with electronic engineers, Cusack simulates the behaviour of proteins to understand how they control the formation of shells, using very small microfluidic devices, or what is called ‘lab on a chip’ technology. The fruits of this research may lead to the development of therapies for growing new ‘bio-compatible’ bone, as well as very strong and lightweight materials for multiple uses.
Even though it may seem like a piece of science fiction to be able to ‘grow’ new bone, there is evidence that such ideas have been around for millennia – e.g., the ancient Mayans implanted worked fragments of shell into their jaw bone as an early form of dental implant. Initially this was thought to be a burial ritual, inserting shell fragments after death, but recent analysis shows that these shell implants were actually primitive dentures which reacted extremely well with living human tissue, with the shell being totally absorbed into the jaw bone – an example of osteointegration.
It is hard to imagine that while vertebrates commandeer calcium phosphate for skeletal fabrication (bones), invertebrates commonly use calcium carbonate (CaCO3) to manufacture external structures such as shells. This juxtaposition of phosphate and carbonate is often described as the ‘Bone–Shell Divide’. According to Cusack, current research indicates that synthetic bone based on nacre (mother-of-pearl) implants does not induce an immune response, being completely integrated into the bone. This makes nacre an extremely attractive biomaterial with potential applications in therapeutic bone formation.
However, as with the need to understand the intricacies of protein involvement in shell formation (biomineralisation) and how this understanding is crucial to accurate climate estimations, so it is equally important to understand why or how invertebrate nacre is so readily accepted in a vertebrate bone environment. Is it the regular, uniform topography of nacre, or the chemical signals in the proteins embedded in the shell – or perhaps both? The challenge is to devise robust experiments that will answer these questions, and here again, Cusack will cross into another domain – that of cell biology.
This departure from ‘conventional’ biology and geoscience reflects the dramatic advances which have taken place in biomineralisation during Cusack’s career, and this in turn is changing the way geoscience is taught, exposing students to the wonders of biology and microfluidics, as well as other more traditional subjects. Understanding how stem cells and proteins produce shell or bone is not just for biologists interested in future advances in health care, but for everyone in geoscience interested in climate change or in the evolution of the planet millions of years ago.