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Getting to Know a Deadly Bacteria

Postdoc-stipendium i Danmark | 04/05/2018

Associate Professor Rikke Schmidt Kjærgaard nearly died from a bacterial infection. It led her to a project on making a visual encyclopaedia of Streptococcus pneumoniae, the bacteria that almost killed her, to advance our understanding of how pneumococcal infections work so we can create better and faster treatment.

By Rikke Schmidt Kjærgaard, PhD, Associate Professor at Interdisciplinary Nanoscience Center, Aarhus University & Co-founder and CEO of Graphicure & Director of the Danish Science Club

Sometimes research gets more personal than you want. I nearly died from a bacterial infection that sent me five months in hospital. This fundamentally changed my perspective on my own research on visualising molecular and medical data. 

It thus led to a project on making a visual encyclopaedia of Streptococcus pneumoniae, the bacteria that almost killed me, to advance our understanding of how pneumococcal infections work so we can create better and faster treatment. 

The grant from the Carlsberg Foundation supporting a pure research project facilitated the making of the start-up company, Graphicure, dedicated to make digital tools to understand and monitor personal health data.

A Deadly Bacteria

Figure 1: Overview of the Pneumococcal Watercolour. The upper image is a whole-cell digital illustration of the pneumococcus. It has a central nucleoid region with purple genomic DNA. The surrounding cytoplasm is in different shades of brown enclosed by the yellow cell membrane. The green grid-like structure is the cell wall, with integrated teichoic acids. The strands further out are capsular polysaccharides. The rectangles indicate the positions of the eight watercolours. The eight watercolour paintings of the cellular sections indicated in the upper image with key proteins highlighted in light purple are shown as: 1 Protein synthesis; 2 Carbohydrate metabolism; 3 Cell wall synthesis; 4 Cell division; 5 Teichoic acid synthesis; 6 Virulence; 7 Transformation; and 8 Pilus synthesis. [From F E M S Microbiology Reviews, 41(6), 2017: 854–879].

Streptococcus pneumoniae is a human pathogen. It causes serious health problems worldwide and has a high mortality rate with an estimated one million children dying from pneumococcal infections every year. 

The polysaccharide encapsulated bacteria live in the human body and can lead to a number of illnesses ranging from sinusitis and bronchitis to pneumonia, meningitis and sepsis. There are more than 90 different strains of Streptococcus pneumoniae and although pneumococcal vaccines exist, global resistance to antimicrobials is an increasing problem. 

Scientists have uncovered the evolutionary history of Streptococcus pneumoniae. We know the basics of how it works as a pathogen and we are acutely aware that a global vaccination programme will significantly decrease hospitalisation and mortality, especially in the developing world, which will help to reach the UN’s Sustainable Development Goal 3. But we know very little of the unpredictability of why things sometimes go terribly wrong very quickly and in many cases lead to sudden death.

My Personal Story

In January 2013 my research became personal at a completely new level as I was struck by a pneumococcal infection. In a few hours I went from a perfectly normal well-functioning human being to someone suffering from cardiac arrest, septic shock, multi-organ failure, long-term coma and complete bodily paralysis. I spent two months at an intensive care unit and three months at a rehabilitation centre. 

The first two weeks I was in a deep coma and only gradually returned to the surface merely able to communicate by blinking, incredibly, without any brain damage despite multiple blood clots and a large haematoma in my brain. It took almost two months with my life balancing on the edge and a lot longer to know whether I would ever be able to continue the life I was leading and return to work as a researcher on molecular and medical visualisation.

My illness came as a complete shock with no warning whatsoever. I was in my late thirties and in good health. This was not supposed to happen and certainly not so quickly. I was saved and got back on my feet, but only through lucky timing with very poor odds in my favour, exceptional medical attention, and a lot of care, support, therapy, and hard work. 

To pass on my knowledge of what it’s like to wake up from a coma, learn how to breathe, walk, talk, eat, and drink again, I have put my personal experience in a book (The Blink of an Eye: How I died and started living, London 2018 / Danish translation: Blink: Da jeg mistede livet og lærte at leve, Copenhagen 2018).

Figure 2: Examples of Watercolours. From the left: Pneumococcal carbohydrate metabolism; Pneumococcal cell wall synthesis; and Pneumococcal virulence. All done do scale in a x 2,000,000. [Modified from F E M S Microbiology Reviews, 41(6), 2017: 854–879].

The Molecular Landscape of Streptococcus Pneumoniae

It is extremely rare for anyone to survive what I have been through and afterwards I felt it as both a privilege and an obligation to use my knowledge and expertise as a scientist to communicate what a person go through in such a situation. But more than that, I wanted to apply my scientific skills to increase our knowledge of Streptococcus pneumoniae to help researchers better understand how the bacteria works and thus,  eventually, support development of future clinical treatment.

Consequently, once out of hospital I decided to use part of my Carlsberg Foundation grant to investigate the molecular landscape of Streptococcus pneumoniae by constructing a visual encyclopaedia, collecting and combining all elements of the cell in one illustration designed to generate an understanding of the complex functions of the bacteria. 

Never before have the internal structure of Streptococcus pneumoniae been visually represented as we did it with ink and watercolour paintings. The technique is adapted from Dr David Goodsell from the Scripps Research Institute in California who makes the most beautiful molecular landscapes of large cell environments and also illustrates proteins in the RCSB Protein Data Bank. 

I invited David to join my group in Aarhus and we agreed that my PhD student, Ditte Høyer Engholm, should work on the project as part of her doctoral thesis. David, Ditte and I started to draw all the elements of the cell based on everything we knew about the bacteria, including the atomic structures of individual molecules found in the RCSB Protein Data Bank. 

The technique enabled us to bring together information and data from many different resources and display them in constellations that were either already proven or considered most likely by scientific experts. It is always a challenge to design a cell environment based on real data and to be able to handle great variation in time and spatial scale. This project was no different.

From Pure Research to a Start-Up Company

Developing new methods and guides to advance scientific data visualisation for different target audiences is critical to facilitate a better understanding of scientific knowledge and help decision-making processes at all levels in society. To me, personally, this project has led to a different understanding of the need for improving the way we visualise medical data. 

As a patient, you lose control. You are completely dependent on others - doctors, nurses, family, and friends - and you often find it difficult to understand your own medical data. I decided to use my technical and scientific expertise to make a difference to help patients understand and gain control of their own treatment by facilitating and creating new visual tools for health data. 

I have founded the start-up company Graphicure together with a former colleague from Harvard Medical School and a colleague in Copenhagen.

The support from the Carlsberg Foundation made it possible for me to take the leap from pure research to developing new tools, that will help monitoring personal health data and thus answer to society’s needs for thinking smarter about managing individual treatment and increasing costs relating to ageing populations and a global rise in lifestyle diseases.

Peer-Reviewed Papers Relevant to My Research Granted by the Carlsberg Foundation

1) A Visual Review of the Human Pathogen Streptococcus pneumoniae. / Engholm, Ditte Høyer; Kilian, Mogens; Goodsell, David; Andersen, Ebbe Sloth; Kjærgaard, Rikke Schmidt. F E M S Microbiology Reviews, Volume 41, Issue 6, 2017, Pages 854–879. 
2) Pencil and paper: A unique set of tools facilitate thinking and hypothesis generation. / Wong, Bang; Kjærgaard, Rikke Schmidt. Nature Methods, Vol. 9, No. 11, 06.11.2012, p. 1037.
3) The Aesthetics of Scientific Data Representation. More than pretty pictures. Lotte Philipsen and Rikke Schmidt Kjærgaard (eds.). Routledge, 2017. 

Other Relevant Papers in Scientific Journals and Newspapers as well as Relevant Media Communication

1) Looks Matter: Visual Strategies: A Practical Guide to Graphics for Scientists and Engineers by Felice C. Frankel and Angela H. DePace. / Kjærgaard, Rikke Schmidt; Wong, Bang. Cell, Vol. 149, 22.06.2012, p. 1420-1421.
2) Seeing Streptococcus pneumoniae, a Common Killer Bacteria. / Kjærgaard, Rikke Schmidt; Andersen, Ebbe Sloth. EVA London 2014 : Electronic Visualisation and the Arts . ed. / Kia Ng; Jonathan P Bowen; Sarah McDaid. 2014. p. 319-323.
3) Data visualization: Mapping the topical space. / Kjærgaard, Rikke Schmidt. Nature, Vol. 520, No. 7547, 16.04.2015, p. 292-293.