Cryo-EM takes centre stage

A few weeks ago, the Nobel Prizes for 2017 were announced. This year, 3 of the founders of the field I work in – cryo-EM – were honoured with the Nobel Prize in Chemistry for their work in developing the technique of cryo-EM into something now used near routinely in labs around the world.

After the news was announced, I was asked to write a short explainer/news piece about the technique for the website The Conversation. The Conversation is a website where academics team up with professional editors to write and publish articles, so it was really nice to be asked to write for them. The resulting article is published under a Creative Commons CC-BY-ND licence so can be reused anywhere, so I’ve taken the opportunity to archive it here:

Trio behind method to visualise the molecules of life wins 2017 Nobel Prize in Chemistry

James Streetley, University of Glasgow

Three scientists have won the 2017 Nobel Prize in Chemistry for developing a technique that helps image biological molecules in unprecedented detail. Jacques Dubochet, from the University of Lausanne in Switzerland, Joachim Frank, from Columbia University in the US, and Richard Henderson, from the MRC Laboratory of Molecular Biology in the UK, will share the prize sum of £831,000.

A predecessor of their method – which is known as cryo-electron microscopy – has been recognised by the Nobel committee before. The 1986 Nobel Prize in Physics was given in part to Ernst Ruska for inventing the electron microscope.

As a concept, the electron microscope is similar to a light microscope – a beam is shone through a series of lenses, then through the sample and more lenses, to form an image on a piece of film or camera sensor. Of course, in the electron microscope we are shining a beam of electrons rather than light through our sample.

Unlike light, electrons can’t travel through air – they would collide with the air molecules and get diverted away. This means the electron beam must be contained within a high vacuum system so there are no stray particles to interact with the beam. The lens system is formed of coils of copper rather than the glass lenses of a light microscope – like air, glass would scatter our beam of electrons, rather than focusing it. Instead, we can apply current through the coiled-copper lenses to create a magnet, and we can focus and shape our beam using this magnet instead.

Richard Henderson from the UK is one of this year’s chemistry winners.

However, the need for a high vacuum within the microscope affects what samples can be imaged. Samples need to be dry as liquids would instantly evaporate in the vacuum. Methods for preparing a biological sample like this are to dry them in a protective stain layer or embedding it in resin. However, such dehydration techniques don’t allow us to make the most of the microscope and see the finest details in our sample.

A new era of biochemistry

Cryo-electron microscopy eliminates the need for dehydration. Biological samples such as cells, viruses or proteins are simply frozen within the liquid they are in. As long as we keep the sample frozen in the microscope, the ice protects it from the harsh effects of the vacuum. However, we can’t form just any type of ice. It must be vitreous ice.

This ice doesn’t form crystals, like in a home freezer, where the water molecules rearrange into an ordered pattern. Instead, they are frozen fast enough that they stop moving as they were. It is as if we hit the pause button on liquid water. It was the discovery of how to create vitreous ice that earned Dubochet his share of the prize.

Since then, many laboratories around the world have adopted the technique of cryo-electron microscopy, aided by semi-automated machines for preparing samples within vitreous ice. The earliest work began with looking at viruses, but advances in microscopy and related technologies has seen this expand across a whole size range from tiny individual proteins (around a millionth of a centimetre), through to “molecular machines” consisting of proteins assembled together. “Motor proteins”, such as myosin, are examples of molecular machines – they are responsible for muscle contraction. It is also possible to image bacteria and sections of human cells.

By analysing these images with computers we can calculate how the particle would have looked in 3D in order to produce that image. It’s similar to looking at a shadow and working out how the object that made it looks. Devising methods to do this is part of what Frank was honoured for.

Once we have a 3D model for how a virus or molecular machine is structured, we use that to understand how it functions. Henderson was the first to show that cryo-electron microscopy could be used to obtain the most detailed of 3D models – at atomic resolution. Often, other laboratory methods can tell us “what” a molecular machine does, but with detailed 3D models, we can look inside these machines and understand “how” they do it.

3D image of the Giant Mimivirus.
Structural Studies of the Giant Mimivirus. PLoS Biol 7(4): e1000092. doi:10.1371/journal.pbio.1000092, CC BY-SA

Having a basic understanding of how these machines work, we can start investigating diseases. What happens when such machines don’t work? Or in the case of bacterial or viral infection, what can we do to disrupt their molecular machines? A recent example of this is the Zika virus: scientists used cryo-electron microscopy to rapidly determine the structure of the Zika virus last year. This has already led to follow-up research looking at how to find drugs against the virus. Scientists have also managed to look at proteins involved in antibiotic resistance using this method.

The ConversationThe technique is already achieving results that were unthinkable a few years ago – both in terms of the small size of biological molecules that can now be imaged, and in the detail that can be seen in them. Future advances will continue to widen the possible samples that the microscope can be applied to: small, irregularly shaped objects, molecules only present in small amounts, looking at mixtures of particles or even molecules still present within cells.

James Streetley, Post-doctoral researcher, University of Glasgow

This article was originally published on The Conversation. Read the original article.

University of Glasgow Public Holiday Calendar

After searching for a public calendar with all the University of Glasgow public holiday dates in, I thought I’d share my own in case it’s useful to anyone else.

Simply add this link to which ever calendar program you use.

I’ll endeavour to keep it up to date when the University next updates their list of public holidays.

The end draws near – the PhD viva

Submitted PhD thesis

Submitted PhD thesis

A few months ago, I submitted my PhD thesis. After all of the preparation and writing, submitting was somewhat of an anti-climax. This is because submitting those nicely bound volumes means nothing unless someone is going to read and examine them to determine if the work they contain will earn you the degree and the right to call yourself Dr.

In the UK, these examinations often happen some time after submitting, in a process known as the viva. These exams involve the examiners coming to the university/institute and conducting a private, face-to-face examination of your knowledge and the work presented in the thesis, often over a number of hours.

All this is purely explanation of the main point:

I had my PhD viva on Monday and I passed!

I passed with the most common outcome; minor corrections. This means that whilst I have passed, the examiners would like some changes to be made before the final version of record is submitted. It is only when they are happy with those changes that I will officially earn the degree.

For now, I’m beginning to come down from the celebrations and start working towards the corrections. So it is still not yet the end; I think the real closure will happen when the award letter and certificates are in my hands.

3 years and 9 months

Submitted PhD thesis

Submitted PhD thesis

Yesterday, I submitted my PhD thesis! The culmination, to the day, of 3 years, 9 months of work, distilled into 145 pages. It means that I can now return to “normality”, having become somewhat of a hermit over the last month whilst I pulled out all the stops to get it completed.

It’s a great relief, and I hope I don’t need to write a document that long again for a while. It’s also not over yet though. For those who don’t live in the academic bubble, I just thought I’d explain what this means, and after what point I’ll officially “get” the degree.

What happens next?

Currently, the university is looking after my two submitted copies, until two people (one within UCL and one from outside) can be found to conduct an examination. They will then read the thesis and after that, the 3 of us will sit down in a room and they’ll question me on it – this is the oral exam or ‘viva’.

The outcome of this meeting will decide whether or not I am awarded a PhD. The most common outcome is “minor corrections”, where the examiners will award the PhD on the condition that various mistakes are corrected or additional information added before the final version of record is produced. This is version that will end up in the library at UCL. Once the examiners have approved those corrections; then I’ll be Dr James. So it’s not over yet, but the end is in sight 🙂

Katherine Esau – Ada Lovelace Day 2013

This is the first year that I’ve participated in Ada Lovelace Day, and I decided to pick a woman from history, related to my own field and who I’d not heard of previously, so that I’d have to do some research. I came across the plant anatomist and later electron microscopist, Katherine Esau.

Katherine Esau

Katherine Esau working at the electron microscope - Copyright Cheadle Center for Biodiversity and Ecological Restoration

Katherine Esau working at the electron microscope – Copyright Cheadle Center for Biodiversity and Ecological Restoration

Katherine Esau was born in the city Yekaterinoslav, in the then Russian Empire (now Dnipropetrovsk, Ukraine) in 1898. It was in Russia that she received her early education, until 1917, when the Russian revolution and later German occupation of Ukraine prevented her from completing her studies at the Golitsin Women’s Agricultural College, Moscow.

Esau and her family fled to Germany, moving to Berlin. Here, she was able to continue her studies by enrolling at the Berlin Landwirtschaftliche Hochschule (Agricultural College), completing them in 1922.

Later in 1922, the Esau family moved again, this time to California, USA. It is here that Esau made home for the rest of her life. After some short term jobs, her research career began in earnest with a job at Spreckels Sugar Company. Her project was to develop a sugar beet resistant to curly top disease, a virus carried by beet leafhoppers. This research led to her gaining a position doing similar research as a graduate student at UC Davis in 1927.

Unfortunately (or perhaps fortunately, given Esau’s later success), this project turned out not to be viable at UC Davis, and Esau’s attention was turned to plant anatomy and the effect of the curly top virus on the plant. For this research she was awarded a PhD in 1931.

Esau stayed within the University of California for the rest of her career, first at Davis and later at Santa Barbara, and continued researching the same themes; plant anatomy and virus-plant interactions. In particular, Esau studied the phloem, the tissue that distributes nutrients throughout plants and how viruses such as curly top use this to spread, as well as studying healthy plant anatomy.

My interest in Esau comes from her later work, setting up an electron microscopy laboratory and using this technique to study virus-diseased plants. These are techniques not a million miles away from those I use to look at cells today. Much of this work was carried out after Esau retired, as despite retiring in 1965, she continued to work for many more years, including supervising PhD students.

In addition to her research and teaching, Esau also wrote and illustrated two key textbooks in plant anatomy; “Esau’s Plant Anatomy” and “Anatomy of Seed Plants”, both of which continue to be on university reading lists today, amongst many other books and publications.

During her career, Esau picked up many awards for her work, including the National Medal of Science in 1989, Certificate of Merit from the Botanical Society of America in 1956, and election to the National Academy of Sciences in 1957. She became only the sixth woman to be elected to the Academy. She was also president of the Botanical Society of America and now gives her name to one of their awards, the Katherine Esau Award, given to “the graduate student who presents the outstanding paper in developmental and structural botany” at their annual meeting. UC Davis also runs a post-doctoral fellowship in her name.

As part of her autobiography and oral history in 1991, David Russell asked her about women in science and her experience:

When I first arrived in the United States, many people expected me to do just ordinary things, housework and getting married and so forth—the same routine. But I was more ambitious.


I never worried about being a woman. It never occurred to me that that was an important thing. I always thought that women could do just as well as men. Of course, the majority of women are not trained to think that way. They are trained to be homemakers. And I was not a homemaker.

However, on promotion and her former boss, Esau says;

I now learn from people that he actually did not like to have a woman in the department. He did not treat me right, but I didn‘t notice it. I thought that was the way it was done. I never even questioned it. For example, he was very reluctant to give promotions. Nowadays they often jump one step, and people just go right through the appointments very quickly. But at that time, we went six years in each grade. Six years. It never changed. But then when a new director arrived on the campus, he looked at my record and said that I was not getting enough salary. So he raised my salary, but our chairman, Dr. Robbins, would not do it.

And thus demonstrating, in her own words, why we need initiatives such as Ada Lovelace Day and Athena SWAN.

References and further reading

Biographical Memoir from the National Academy of Science
Autobiography and oral history from UC Santa Barbara
Katherine Esau digital archive from Cheadle Center for Biodiversity and Ecological Restoration
Katherine Esau on Wikipedia (this article could do with some love!)

About Ada Lovelace Day

Ada Lovelace (1815-1852) is known as the world’s first computer programmer for her work with Charles Babbage on his Analytical Engine. She gives her name to a Ada Lovelace Day, in mid-October each year where we “celebrate the achievements of women in science, technology, engineering and maths” (STEM). The day is generally marked by people creating and sharing blogposts, videos and other material about an inspiring woman in STEM.

Electronic Lab Notebooks


Every time I have to write a report, prepare a presentation or meet with my boss, I curse the fact that I can’t just “+F” through my lab book and find those conditions/results/images that I’m looking for.

Of course, with an electronic lab (note)book (ELN), that would be perfectly possible. I see that there are plenty of options; purpose-built or general, local or web/cloud, free or commercial.

At the moment, I’m contemplating a locally hosted WordPress blog, because it is what I know already and it’s easy to set up, but I’m totally open to other solutions. All I know is that I’d like it to be both local and free.

Does anyone have any experience with using Electronic Lab Notebooks and have any advice or preference? I’m all ears.

Also, how about image tagging, like iPhoto or Lightroom but for micrographs? I can’t count how many times I’ve looked for “the kinda round one” or “the one with the weird speckles”…

Joining professional societies

As a PhD student in the life sciences, there are plenty of professional/scientific societies vying for me to join them. These range from the very general, covering all science such as the AAAS, through the general biology (Society of Biology) down to specific fields (Biochemical Society) or techniques (Royal Microscopical Society). Most seem to come with a student rate, subscription to the society’s journal and some obscure postnomial letters. Perhaps most importantly, becoming a member often entitles you to apply for travel funding, as hapsci pointed out.

On the other hand, joining a society requires outlay of some (normally small for student) membership fee, pestering your PI to sign a form stating you are student of a relevant discipline and for the travel grants, anticipating when you want to travel as some societies require you to have been a member for some time prior to asking them for money.

So I’m putting it out there; is it worth joining these societies as student, and if so, how many?

Is using an academic title automatically an ‘argument from authority’?

We are bombarded with ‘expert opinions’ every day in the media, both printed and broadcast, and many of these people are presented to us with their title: Prof, Dr, PhD, FRS and the like. An example might be this recent story on sleep deprivation and stroke from the Guardian, which is followed throughout.

My questions are: does including their “rank” in the scientific hierarchy automatically say to the audience “you should believe this person for they are more qualified than you“, is this committing an ‘argument from authority‘ and does this even matter at all?

The first question translates basically to whether or not an academic’s title is optional. On the one hand, they’ve earned the degree/accolade by working pretty damn hard and deserve to be called by it. In 3 years time, when (hopefully) I finish my PhD, I’ll be pretty cheesed off if ‘Dr’ doesn’t get written down in the right places. On the other hand, within science (certainly biology/biochemistry), people don’t much use their titles. At the institute where I work, titles are basically relegated to the telephone directory and a handful of email signatures. They certainly don’t appear on published papers, so why in the press release and press coverage. (As an aside, this is different in the medical world such as the BMJ, The Lancet and NEJM, where author qualifications are published). If they aren’t on the paper itself, I think that says to me that they aren’t needed in the press coverage, but I’ll admit that it’s an open question.

Does the inclusion of these titles confer authority on to whatever quote their holder is giving? I think they probably do. This might not be the intention in science reporting but it has that effect. Why else would people be so keen to use the title Dr, if not to be accepted as an expert in a field?

A better question is whether worrying about presenting a well-qualified expert as an authority figure actually matters? As noble as the Royal Society’s motto might be (nullius in verba – On the word of no-one), equally nobody has time to fact check everything, and qualifications and titles are often a pretty good heuristic for reliability. As Paul Nurse (or perhaps “the Nobel laureate Sir Paul Nurse PRS) recently put to James Delingpole (3m30s), when you go to a doctor, you trust their clinical judgment. You might do your own research and disagree with the consensual position, but that would be a very unusual position to take.

The problem – as there is with all such rules of thumb – is that it is open for exploitation. I alluded earlier to those who ‘pass off’ having more qualifications than they have, often in order to lend their opinion legitimacy, often for monetary gain in the form an endorsement by an expert. Weirdly, this means that every time a title such as Dr is used legitimately, it adds weight to all those using the same title illegitimately. A reverse problem can also occur – someone with a legitimate qualification, in a relevant field presents a maverick view rather than scientific consensus and can be spectacularly wrong, but still taken “on authority”. Think Andrew Wakefield and the disproven MMR/Autism link for an example.

On balance, I’m not sure that there is a right answer to the use of academic titles. To me they are a mark of respect and achievement, not authority and certainly don’t mean that everything the holder says is true and sacrosanct, but I’m not sure that is always how they are taken.

“James Streetley BSc (Hons) MRes

Science is Vital

Supporters at the rally

Supporters at the rally

Yesterday, I attended (and helped marshall, as evidenced here) the rally for an important campaign called Science is Vital. It is a campaign against any proposed cuts to the science budget, when the spending review is published later in the month. I urge anybody who hasn’t already done so to: check out their website which details all the reasons why continued investment in science is a necessity, sign their petition and write to their MP about the campaign. It was a fantastic afternoon and great to meet up with so many people that I’ve heard about or briefly tweeted @ them but never spoken; even if it was under unfortunate circumstances with the prospect of cuts hanging over all our heads.

This campaign is more than just a self-interested group getting antsy about a policy they don’t like. Yes, many of the people who have signed the petition are scientists who are understandably worried about their own careers. I am also worried about what the state of biomedical science will be when I start looking for my first position after finishing my PhD in 3 years time.

This is about more than that though. We are saying

We already don’t have enough money to do all the research we need, with only around 20% of grant proposals finding funding, and yet we greatly ‘punch above our weight’, in almost any metric you pick; number of World-class universities, citations per researcher, papers produced against spend. We can’t get more efficient. We are already at the limit.

And it isn’t the scientists that will be the biggest losers in this. They can move to other world-leading institutions in the US, Japan, India, Australia, Germany and others. It is society that loses out, as we have to become reliant on the work of other countries to fulfil our scientific, technological and engineering needs.

The Campaign for Science and Engineering has plenty more on the economic reasons why science funding is a poor judgment, so if you like facts and figures, head here. The Science is Vital campaign has also collated photos and other reports from the event and the Pod Delusion has podcasts of all the speakers and some reporting from the rally. The rest of my own photos from the event can be found in this Flickr set.

Regulation of Old Wives’ tales-type medicine?

Handing out diplomas

This morning, Voice of Young Science stood outside the Department of Health on Whitehall, assessing passers-by and awarding them diplomas in “Traditional Medicine of Old Wives’ Tales”.

The reason for this is a little bit protracted, but bear with me and I’ll explain why they were doing it, and why it is important to take notice. The story started over a year ago when the Department of Health published this document, a consultation on the statutory regulation of a number of Traditional Medicine Systems. This seems to have sent alarm-bells ringing for a number of people, for a number of reasons:

  • the proposed registration scheme doesn’t require a practitioner to have any training
  • the scheme doesn’t require evidence of efficacy (that the treatments work), merely that they are traditional
  • registration from a Government body such as the Department of Health or a subsidiary implies endorsement and legitimises these treatments.

These concerns are found in the Sense about Science submission to the consultation (from October 2009) and in the flyer for today’s event.

It is the first point which VOYS have taken the most issue with: lack of training and the implication that “[traditional] practitioners have the knowledge, skills and attributes of qualified medical practitioners”. This leads on to today’s exploits, which aim to show just how little knowledge is required to proclaim Old Wives’ Tales-type traditional medicine – so little knowledge, that even I got a Diploma:

My traditional medicine Diploma

I’m not entirely sure what the significance of today is, as other than the original consultation, I haven’t been able to find any more on the matter from the Department of Health, not even a response to the consultation. There has also been a little bit of criticism over the choice of “Old Wives'” as the type of traditional medicine portrayed here, as ageist, sexist and failing to take account of historical context, when conventional medicine wasn’t exactly evidence-based. I also think that the way today’s event was done, it looked more about the ease of obtaining a qualification rather than about regulation in traditional medicine.

However, none of these snaggles should stop us from being seriously worried at the point made today though. Regulation and accreditation of alternative medicine only serves to legitimise this sort of pseudoscience and helps it to gain another foothold in society, similar to the platform that traditional medicine courses in universities has provided. We must make every effort to ensure that money isn’t wasted on regulations that could ultimately hinder medical care.