selfless in seattle

Actually, this post has nothing to do with Seattle. I just liked the title. The theme, eventually, is science leadership through altruism. But to get there, first I need to relate a story that has been on my mind the past week or two.

It’s a story about my highest cited paper. Which happens to be a single author paper. Yet this paper almost didn’t get submitted.

According to Google Scholar (2 Jan 2017) this paper has 785 citations (579 according to the journal). And though it’s more than 20 years old, it still averages 30 cites per year. The paper reports on a protein fold that has been used in Nature to deliver many different enzymatic functions, and in so doing has evolved the most incredible and beautiful diversity of protein architectures.

It is a most enchanting protein fold. (I may be biased).

Sure, after 20 years the paper is probably in need of an update. But as you might imagine, I am inordinately proud of this piece of work. Especially given that at the time I wrote it, I almost talked myself out of submitting it. Funny how things work out, isn’t it.

Let me explain.

A few years before that paper was published, I solved the crystal structure of a then recently discovered bacterial protein (DsbA) that had no detectable sequence relationship to any proteins of known structure. That information implied that its structure would be completely novel. At the time, I was a postdoctoral researcher at Rockefeller University. The structure determination was challenging, for a number of reasons that I won’t bore you with. Suffice to say that it required some pretty nifty labwork to wrangle the structure out of that crystal. The important point is that to everyone’s surprise, despite the lack of sequence similarity, the structure revealed that my protein was related to an already characterised protein (thioredoxin). Unexpectedly we had found distant protein cousins – but it wasn’t their DNA that gave their relationship away, it was their shape.

I published the structure determination as a short correspondence – which meant there wasn’t enough space to wax lyrical about the surprising relationship between the two proteins. So I followed up that line of enquiry separately. I collected all the published protein structures that contained that fold, I analysed their sequences, their structures, their similarities and differences, I wrote up a draft and sent it to my two co-authors for comment. One co-author was my postdoctoral supervisor – Prof John Kuriyan. The other was a collaborator who had worked on the structures of some of the distant cousin proteins. By this stage though, I had moved to the University of Queensland where I was setting up my own lab. John Kuriyan had very generously – selflessly – encouraged me to take the project with me when I left his lab. (Thank you John!)

Then came the spanner in the works. John insisted that this structural bioinformatics paper was mine; and that he should not be an author. After John took his name off the paper, the other co-author followed suit. Eek. I was on my own. As a new lab head I had sort of been relying on these two to help me write the cover letter, respond to reviewers’ comments. And, you know, give the paper some cachet. Now, the cachet would be left entirely to me. My first reaction when the two co-authors jumped ship was that they must think the paper was a dud. Such is impostor syndrome thinking.

But needs must – I hadn’t had any papers published for 18 months because of the move to Australia and setting up a lab. So I timidly submitted the paper to a good journal and – surprise, surprise – it was sent out for review. The reviewers were supportive. The paper was accepted with minor changes and then published. The rest, as they say, is history.

This story of my almost-not-submitted-top-paper is front of mind at present because:

• I am writing a grant application that requires me to highlight my ten best papers

• there is an upcoming celebration of John Kuriyan’s 30 years as a lab head

• I am reminded of Prof Ben Barres of Stanford University.

On that last point, I was deeply shocked and saddened by the news that Ben passed away recently. Ben – a renowned neuroscientist – had a unique perspective on equity and diversity. He was openly transexual.

In a 2006 commentary he told the story of how, soon after transitioning, he overheard a colleague say “Ben Barres gave a great seminar today, but then his work is much better than his sister’s”.

I never met Ben, but I felt I had. He was inspirational, a champion of those marginalised in academia. He spoke truth to power.

In one of many tributes to Ben, I noted the words of his former postdoc. “Ben told me, ‘Take this work with you to your new lab, Beth. Nobody can do it better than you.’ Mentors aren’t always so generous about ceding areas of research initiated in their lab to trainees headed elsewhere. But Ben was a very special person. Not only was he an incredible scientist, but he also cared deeply about other people, especially his trainees. We were his kids.

Ben believed so deeply on the importance of this point that he wrote an opinion piece in Nature published in August 2017 while “dying of stage four pancreatic cancer“. He argued that lab heads should let junior researchers take their projects with them when they start their own labs because it drives innovation and discovery. That’s what he did for his team. And JK did for me.

So how about it research agencies and organisations? Let’s incentivise innovation. Enable altruism. Support real leadership in science. Metrics for selflessness now!

Vale Ben Barres

#crystalcakes

This year is the UNESCO International Year of Crystallography (IYCr). And today – August 12th – is the last day of the International Union of Crystallography (IUCr) Congress and General Assembly being held in Montreal where more than 2,500 crystallographers from around the world have gathered to discuss the latest results, methods and analyses. The Congress is a bit like the Olympics for crystal scientists. It’s held every 3 years, and bidding to host the event is fierce. The 2017 Congress will be held in Hyderabad, and – just announced today – the 2020 Congress will be held in Prague. I hope I can make it to both!

The UNESCO 2014 IYCr is an exciting time for crystallographers. There are so many things to celebrate: recent centenaries including those of the first evidence of diffraction of X-rays from a crystal in 1912 (by von Laue, Friedrich and Knipping), the derivation in 1912 of the equation relating planes of atoms in a crystal with the X-ray diffraction pattern (by Lawrence Bragg – hence Bragg’s Law) that led to the first crystal structure determination in 1913 (by Lawrence Bragg and his father William Bragg), the first Nobel prizes to crystallographers (von Laue in 1914, father and son Bragg team in 1915). It’s a source of special pride in Australia that Lawrence Bragg, born and raised in Adelaide, the first Australian Nobel Prize winner, also holds the record for being the youngest ever Nobel Prize winner (he was just 25).

To help mark IYCr there have been ceremonies, stamps, coins (well 1/5th of a coin), sculptures, crystal blogs, photo competitions, videos and public lectures. But you don’t have to go global, or even national, to enjoy crystallography or to learn more about this fascinating science. This year, the Martin lab has gone crystal with its birthday cakes. On the suggestion of Dr Gordon King in the team, we decided to make our birthday cakes crystal-themed. And we chose to celebrate not just our own birthdays but also those of crystallography pioneers. I’d like to share with you 4 of the 15 amazing #crystalcake creations we have enjoyed to date.

Sodium Chloride #crystalcake by Dr Róisín McMahon

First up was Dame Kathleen Lonsdale – her 101st birthday was celebrated on Jan 28th. Dame Lonsdale was a fascinating person: born in Ireland, the last-born of a family of 10 children, she became the first woman Fellow of the Royal Society (1945), and the first woman Professor at University College London (1949). She was also “a committed pacifist and served time in Holloway prison during the Second World War because she refused to register for civil defence duties or pay a fine for refusing to register“. Lonsdale worked with William Bragg, who actively promoted women in science. Indeed, in her own wordsIn 1929 my first baby came and I found it rather difficult to do everything in the home and also find time for ‘Arbeit’ (research); so I wrote to W.H.B. (Bragg senior) and he persuaded the Managers of the Royal Institution to give me a grant of £50 for one year with which to hire a daily domestic helper. Her name was Mrs. Snowball (it really was!) and, with her to wash and clean, I managed to care for the baby, cook and continue the structure analysis of C6Cl6.

NaCl-cake

Sodium chloride crystal structure #crystalcake, designed and made by Dr Roisin McMahon

Gordon King, our #crystalcakes MC, noted “Her work included studies on the crystal structures of hexamethyl benzene (1929) and diamond (1944). Her paper on the structure of diamond (Nature 1944 Vol 153 No3892 p669) finishes with this interesting paragraph: “In some ways the problem of diamond is like a crossword puzzle.  We have clues, but in some cases we do not know the solution; in other cases there seem to be more than one possible solution.  But as Sir William Bragg said many years ago: “There is no cross-word puzzle that can compare in interest with the practical working out of a problem in Physics or Chemistry.  You may say that to work at an amusing thing is not a very noble task.  I can only answer that it makes a very happy life and I think that, if we can increase the number of human beings who find happiness in their work, we shall have gone some way towards creating a better state of things”.

Seems a pity that scientific journals don’t allow musings like this in the discussion any more.

Electron density #crystalcake by Dr Premkumar Lakshmanane

Prem-Magawcake

Electron density chocolate #crystalcake, designed and made by Dr Premkumar Lakshmanane

On June 1, we celebrated the birthday of Helen Megaw. Helen, like Kathleen Lonsdale, was born in Ireland, and her career spanned several decades and several countries and laboratories. She is credited with contributing crystallographic images used in art. “Her electron-density contour map of afwillite inspired both textiles and wallpapers.” Not to mention her Martin lab birthday #crystalcake. Helen received many honours in recognition of her research on the structure of ice and minerals. For example, she was the first woman to be awarded the Roebling Medal of the Mineralogical Society of America (in 1989, when she was 82). And according to Wikipedia, she has an island and a mineral named after her.

Ribosome #crystalcake by Dr Maria Halili

ribosome

Ribosome #crystalcake, featuring the 50S and 30S subunits, and made from chocolate cake, fondant, chocolate sweets, licorice and marshmallow. Designed and made by Dr Maria Halili

Ada Yonath, born in Israel on June 29 1939, shared the Nobel prize for Chemistry in 2009 with Venki Ramakrishnan and Tom Steitz for work on the structure of ribosome, the molecular machine that reads RNA and translates that information into the biosynthesis of proteins. Her research began in Dec 1979 and took many years to come to fruition. Ada persisted, and achieved her goal, despite advice from others including this is a dead end road’, and ‘you will be dead before you get there’. 

Photo 51 #crystalcake by Dr Wilko Duprez

Rosalind Franklin was born in London on July 25, 1920.

Photo 51 #crystalcake created from lime tart, Raffaelo, chocolate sweets, cocoa and icing sugar. Designed and made by Dr Wilko Duprez just a few weeks after his PhD was awarded.

Photo 51 #crystalcake created from lime tart, Raffaelo, chocolate sweets, cocoa and icing sugar. Designed and made by Dr Wilko Duprez just a few weeks after his PhD was awarded.

She died tragically young, at the age of 38. Martin lab celebrated what would have been her 94th birthday a few weeks ago, with a #crystalcake representing her famous photo 51. This diffraction image of DNA, described by JD Bernal as the most beautiful X-ray photograph of any substance ever taken, and more recently as the most important photograph ever, led to the molecular description of DNA – the blueprint of life. Crick, Watson and Wilkins were awarded the Nobel prize for the structure of DNA. Rosalind Franklin’s untimely death meant she missed out.

There’s a bit of a theme

Yes, it’s true. I have focused on women crystallographer #crystalcakes in this post. They have such wonderful stories to tell. And that’s even without the Dorothy Hodgkin #crystalcake. Crystallography has a rich tradition of women pioneers, though perhaps less so in recent times. One might wonder what has changed recently. Perhaps there are clues to be found in the stories of Lonsdale, Megaw, Yonath and Franklin.

In any case, there are plenty more #crystalcakes to come this year, and plenty more stories to discover.

**updated on 15th Aug with corrected dates**