The Science Behind the Image Contest Winners: Light Trails of Receptor Tyrosine Kinase EphA2

The BPS Art of Science Image Contest took place again this year, during the 60th Annual Meeting in Los Angeles. The image that won second place was submitted by Thomas Newport, a PhD student at the University of Oxford. His image shows simulated dynamics of the ectodomain of the receptor tyrosine kinase EphA2 (shown as glowing lines) as well as different conformations that highlight the possible movement of this receptor relative to the membrane surface. Newport writes here about the image and the science it represents, as well as his experience as a first-time BPS Annual Meeting attendee.

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The Biophysical Society’s 2016 meeting was unlike any other conference I have attended in my admittedly fairly short academic career. Thousands of posters, talks, and exhibits clamour for attention over a packed six day schedule. Distinguished professors haggle over conclusions with terrified grad students, while suited salespeople draw in new customers with the promise of free bags, USB drives, and flat-pack microscopes.

Probably the highlight of this, my first Biophysical Society meeting, was winning second prize in the Art of Science image competition, or as my supervisor helpfully emailed me a few minutes later, “congratulations, you’ve won second prize in a beauty contest, collect $10.” The competition: ten gorgeous images, some computer generated, some from microscopes, telling a selection of stories from across the vast field of biophysics.

My image was developed in collaboration with Matthieu Chavent, and shows simulated motions of a key signalling protein as it interacts with the cell membrane. His paper explains more of the scientific background and is well worth a read. Matthieu had already visualised the protein using VMD, a popular open source visualisation tool for molecular dynamics simulations, and traced the paths followed by several atoms as the protein moved between two states. By this point my enthusiasm for digital art and 3D visualisation was fairly well known so we met up to discuss turning this data into art.

Blender3D has been my tool of choice for 3D digital art since I was in high school. It’s open source, has great developer and user communities, and can be used for anything from game development to movie production. Working on the data in Blender gave me complete control of the scene, letting me get the composition, lighting and materials just right. I drew inspiration from long-exposure “light painting” photography, where movement can be captured using trails of light. The light trails were probably the most difficult part to get right – transparent and glowing enough to look ethereal but clear enough to be easy to follow.

It seems to have been a hit – the image has been used as the cover of Structure journal and even appeared on the 2015 Biochemistry Department Christmas card (Matthieu even photoshopped some festive hats onto the proteins, although sadly they didn’t make it to the final card). I’ve run a couple of courses teaching Blender to structural biologists, and it definitely seems like a few people were put off by easily fixable data compatibility issues. Once I’ve got a moment free I’d really like to improve the way Blender handles structural biology data to take some of the data wrangling out of developing scientific art. If you’d like to help, you can find me on GitHub or Twitter (@tnewport).

Concepts in biophysics and structural biology are often most effectively communicated through images, from the iconic double helix of DNA to Jane Richardson’s now ubiquitous protein ribbon diagrams. New technologies are creating new ways for us to tell scientific stories in visual media, as still images, videos, and interactivities. This year’s BPS Art of Science competition showcased some amazing works of art that have come out of these advances, and I’m looking forward to an even tougher competition next year.

The Science Behind the Image Contest Winners: Influenza A Virus and Mammalian Plasma Membrane Models

We are starting off the week taking a look at the science and scientist behind the scenes of the influenza A virus model that won second place in the Society’s 2015 Image contest.  The image was created by Heidi Koldsø, a postdoctoral researcher in Mark Sansom’s group in the Department of Biochemistry at Oxford University. Koldsø moved to Oxford from Denmark three years ago on an independent fellowship from the Alfred Benzon foundation.  Her research is mainly focused on understanding in details how membrane proteins, which are the largest pharmaceutical target, interact with their surrounding environment. She notes that understanding of not only the membrane proteins but also the lipids surrounding them is of the utmost importance – for example understanding how antimicrobial peptides target bacterial membranes and not human ones. Also, as illustrated in this image, if it is possible to understand how a virus interacts with the cell membrane, scientists can hopefully come up with solutions for better antiviral pharmaceuticals.

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The images of the molecular models that captured the attention (and votes) of the 2015 BPS annual meeting attendees were constructed using the molecular visualization program Visual Molecular Dynamics (VMD). Ambient occlusion shading and rendering techniques were applied to the images within VMD. The image depicts an influenza A virus model in close proximity to a coarse grained mammalian plasma membrane model. Due to the large number of particles within these models we used a powerful workstation with lots of memory and a recent graphics card to create the image.

I chose this particular image to submit to the contest because it encapsulates both the achievements we have already made and those that are to come and it was a natural choice as an image that represents the science we study, the hard work we put into it and the potential real world applications it has. Both the project on the outer envelope of the influenza A virus and the large scale cell membranes are very ambitious and time consuming projects and are the result of a lot of hard work from a number of people. This image is the culmination of those two separate endeavours but also the beginning of the next.

When looking at the image, I hope it inspires the viewer to appreciate the current advances in computational modelling and how far we have come in our efforts to probe very real and relevant problems. The image is not only a pretty representation of a simulation as being able to visualize systems at these length scales provide us with unique insight to how these elements might look in vivo. The image does not only give a first glimpse of the molecular details of virus interactions with the membrane but also hopefully provides scientists and the general public with something that they can relate to and will hopefully promote intelligent discussion.

Supporting Scientific Information

The image is a product of the combined efforts of two large ongoing projects in the Sansom research lab at Department of Biochemistry, University of Oxford. The specific research from which the structures are taken involves performing coarse grained molecular dynamics simulations that we run on super-computing resources.

During the last couple of years I have been working on methods to construct complex asymmetric membrane models that allows us to move towards more ‘in vivo’ like systems. Our initial results on studies of complex membranes and the correlation between membrane nano-domains and curvature was published last year (Koldsø et al. PLoS Comput Biol (2014) 10(10): e1003911. doi:10.1371/journal.pcbi.1003911). We have recently started to move toward studying ‘in vivo’ like plasma membrane models at experimental length scales, meaning we are running simulations of systems >100 nm in dimensions and composed or millions of particles.

A complete model of the outer envelope of influenza A virus has recently been revealed, this project was initiated by a previous Postdoc in the Sansom lab,. Daniel Parton (currently working with John Chodera at MSKCC in New York) and has been continued by Tyler Reddy during the last 3 years in Oxford. This Influenza A virion model was recently published in Structure (Reddy et al. (2015) Structure, 23, 584-597).

The image is a result of combining these two projects on the influenza A virus and large scale mammalian cell membranes. We are exploiting the large deformations and curvatures that we observe in the mammalian plasma membrane model to accommodate the virus. This system is extremely complex and large (> 10 M particles) and Tyler and I are currently in the process of equilibrating and optimizing this model. Computational studies of the influenza A virus in close proximity to the cell membrane will potentially provide us with valuable information regarding how viruses enters the human cell during infection.

More information about my research and publications can be found on my website  and the website of my collaborator, Tyler Reddy.