Category Archives: Commentary

Tsar Nicolas II and the curious case of the mismatched bases in his maternal mitochondrial DNA – was Tsar Nicolas II really killed in a cellar in 1917?

The Death of the entire ruling Romanov Family in 1917

In 1917, Tsar Nicolas II, together with his wife, the Tsarina Alexandra, their five children (Maria, Anastasia, Olga, Tatiana and crown prince Alexei), and four servants, was executed and hastily buried in non-marked graves. His death ended the monarchic rule of House Romanov in Russia; no Tsar would ever sit on the Imperial throne again. A house which included famous Tsars Peter the Great and Catherine the Great was literally eradicated overnight.

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Why you should care about startups as a researcher

I was recently awarded the EIT Health Translational Fellowship, which aims to fund DPhil projects with the goal of commercializing the research and addressing the funding gap between research and seed funding. In order to win, I had to deliver a short 5 minute startup pitch in front of a panel of investors and scientific experts to convince them that my DPhil project has impact as well as commercial viability. Besides the £5000 price, the fellowship included a week-long training course on how to improve your pitch, address pain points in your business strategy etc. I found the whole experience to be incredibly rewarding and the skills I picked up very important, even as a researcher. As a summary, this is why I think you should care about the startup world as a researcher.

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Chat bots and the Turing test

When I recently tested out the voice activation features on my phone, I was extremely impressed with how well it understood not only the actual words I was saying, but also the context. The last time I used voice control features was years ago when the technology was still in its infancy. There was only a specific set of commands the voice recognition software understood and most of them were hard-coded. Given the impressive advances we have made utilizing machine learning for voice recognition and natural language processing to the point where I can tell my phone: “Hey Google, can you give me a list of the best BBQ restaurants near me?” and it will actually understand and do it, it is interesting that we still struggle with a language based technology that has been around for ages: chatbots.

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A new way of eating too much

Fresh off the pages of Therapeutic Advances in Endocrinology and Metabolism comes a warning no self-respecting sweet tooth should ignore.

“Liquorice is not just a candy,” write a team of ten from Chicago. “Life-threatening complications can occur with excess use.” Hold on to your teabags. Liquorice – the Marmite of sweets – is about to become a lot more sinister.

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Oh lord, they comin’ – a diversity of units

For scientists, units are like money: a few people obsess about them, but the less you have to think about units, the better. And, like switching a bank account, changing your units is usually tiresome and complicated for little real advantage. But spare a thought for the many units that have been lost to the inexorable march of scientific advance, and for the few that are still in regular use.

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Getting home: An ordeal of flight cancellations (& what they actually cost)

Last week, a sizeable flock of OPIGlets went to ISMB in Basel. Also last week, a storm and a radar tower problem over London Gatwick (LGW) and London Heathrow (LHR) led to four of those OPIGlets being stranded in Switzerland. This is a (somewhat accurate) timeline of their ordeal:

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On the Virtues of the Command Line

Wind the clock back about 50 years, and you would have found the DSKY interface—with a display (DS) and keyboard (KY)—quite familiar. It was frontend to the guidance computer used on the Apollo missions, that ultimately allowed Neil Armstrong to utter that celebrated, “One small step for [a] man, one giant leap for mankind.” The device effectively used a command line.

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Seeing the Mesoscale

There’s a range of scales that is really hard for us to see. Techniques like X-ray crystallography and increasingly, cryo-electron microscopy, let us see molecules to atomic level-of-detail. Microscopes reveal organelles in cells, but seeing the molecular ‘trees’ in the cellular ‘forest’ requires a synthesis of knowledge. David Goodsell was one of the first to show us the emergent beauty of the cell at the molecular level, and work carried out in the Molecular Graphics Laboratory at The Scripps Research Institute under the direction of Art Olson has led to a 3D molecular modeling tools like ePMV, autoPACK and cellPACK.

One of the fruits of this labor is the Visual Guide to the Cell, part of the Allen Cell Explorer. It’s well worth a look at how you can explore 3D representations of the cell in a web browser.

The Protein World

This week’s issue of Nature has a wonderful “Insight” supplement titled, “The Protein World” (Vol. 537 No. 7620, pp 319-355). It begins with an editorial from Joshua Finkelstein, Alex Eccleston & Sadaf Shadan (Nature, 537: 319, doi:10.1038/537319a), and introduces four reviews, covering:

  • the computational de novo design of proteins that spontaneously fold and assemble into desired shapes (“The coming of age of de novo protein design“, by Po-Ssu Huang, Scott E. Boyken & David Baker, Nature, 537: 320–327, doi:10.1038/nature19946). Baker et al. point out that much of protein engineering until now has involved modifying naturally-occurring proteins, but assert, “it should now be possible to design new functional proteins from the ground up to tackle current challenges in biomedicine and nanotechnology”;
  • the cellular proteome is a dynamic structural and regulatory network that constantly adapts to the needs of the cell—and through genetic alterations, ranging from chromosome imbalance to oncogene activation, can become imbalanced due to changes in speed, fidelity and capacity of protein biogenesis and degradation systems. Understanding these complex systems can help us to develop better ways to treat diseases such as cancer (“Proteome complexity and the forces that drive proteome imbalance“, by J. Wade Harper & Eric J. Bennett, Nature, 537: 328–338, doi:10.1038/nature19947);
  • the new challenger to X-ray crystallography, the workhorse of structural biology: cryo-EM. Cryo-electron microscopy has undergone a renaissance in the last 5 years thanks to new detector technologies, and is starting to give us high-resolution structures and new insights about processes in the cell that are just not possible using other techniques (“Unravelling biological macromolecules with cryo-electron microscopy“, by Rafael Fernandez-Leiro & Sjors H. W. Scheres, Nature, 537: 339–346, doi:10.1038/nature19948); and
  • the growing role of mass spectrometry in unveiling the higher-order structures and composition, function, and control of the networks of proteins collectively known as the proteome. High resolution mass spectrometry is helping to illuminate and elucidate complex biological processes and phenotypes, to “catalogue the components of proteomes and their sites of post-translational modification, to identify networks of interacting proteins and to uncover alterations in the proteome that are associated with diseases” (“Mass-spectrometric exploration of proteome structure and function“, by Ruedi Aebersold & Matthias Mann, Nature, 537: 347–355, doi:10.1038/nature19949).

Baker points out that the majority of de novo designed proteins consist of a single, deep minimum energy state, and that we have a long way to go to mimic the subtleties of naturally-occurring proteins: things like allostery, signalling, and even recessed binding pockets for small moleculecules, functional sites, and hydrophobic binding interfaces present their own challenges. Only by increasing our understanding, developing better models and computational tools, will we be able to accomplish this.