PhD – 21 months in 

Do you remember my optimistic blog post about finding my bearings in the lab after a month of the PhD? I also included pictures of a failed western blot and slightly crushed centrifuge tubes.

Well, twenty months later and I’m still making mistakes. Often they’re new and different mistakes, which could almost be exciting. But today I made the same mistake and lost a lot of plasmid-growing bacteria (bacteria I am using as work horses to produce specific DNA for me) in a centrifuge (which I subsequently cleaned!)…

Photographic evidence attached.

11th International PhD Student Cancer Conference

A glorious three day bonanza of beer, brains and BRAF. — Tom Mortimer, PhD student at The Francis Crick Institute


On Wednesday morning, June 14th, twenty PhD students from The Francis Crick Institute woke up early and made their way from one of London’s five airports to Berlin. Specifically to Campus Berlin-Buch – the geographic equivalent of Clare Hall Laboratories, situated right next to the M25, the London Orbital Motorway, 25 kilometres from the city centre – home to the Max Delbrück Center for Molecular Medicine (MDC).


On the campus of the MDC

We were attending the 11th international PhD student cancer conference (IPSCC), which was initiated at the London Research Institute (LRI), one of the founding partners of The Crick. In fact, the opening remarks were held by Holger Gerhardt, a former group leader at the LRI. He immediately gave the meeting a political flavour by stressing how important diversity is within research, openly showing his disdain for Brexit.

The conference was organised by PhD students at the MDC for other students studying cancer across Europe, with delegates from the UK, Germany, Italy and the Netherlands. The talks were spread over three days and the topics ranged from in silico computational biology and large-scale genomics approaches to cell signalling and in vivo cancer metabolism. Strikingly, when speakers were given suggestions or asked questions they seemed sincere in their responses, especially when they didn’t know the answers. One of the talks most out of the ordinary was given by Joseph Hodgson from the CRUK Beatson Institute in Glasgow: he uses fruit flies to study the process of weight loss and muscle wasting due to cancer (also known as cachexia).


Joseph Hodgson showing fluorescent images of fruit fly muscle wasting (right)

The prize for the best talk went to Rajbir Nath Batra, from the CRUK Cambridge Institute, who studies DNA methylation dynamics in breast cancer in Carlos Caldas’ group. The best poster by far was created by Cora Olpe, also at the Cambridge Institute, who is trying to understand the chemopreventive effect of aspirin on colorectal cancer in the group of Douglas Winton.


Cora Olpe’s poster made use of Aspirin’s chemical formula to great effect

On the social side of things, conversation was enabled by providing generous amounts of delicious German beer as well as having us participate in career workshops, including on grant writing, conducting clinical trials, science communication and on becoming an entrepreneur. All in all it was great to get the opportunity of meeting the people who might be our future collaborators.

The keynote speakers were Mónica Bettencourt-Dias (Gulbenkian Institute, Lisbon) and Madalena Tarsounas (Institute for Radiation Oncology, Oxford). Lastly, Klaus Rajewsky (MDC, Berlin), a world-renowned immunologist, gave a lecture on his “life in science”. He ended the conference also on a political note, juxtaposing the 1975 referendum on the UK’s membership to the European common market with the Brexit referendum, also stressing how important international collaboration and diversity are within science.

Next year the 12th IPSCC will be hosted by The Francis Crick Institute. We hope to have a great turnout (especially in the face of Brexit) – see you there!


March for Science

London, Saturday April 22nd 2017

The weather is changeable as I leave the flat in the late morning. Sunny spells – dazzling my eyes clad in contact lenses – are abruptly overtaken by the English drizzle that leaves me damp and puzzled because the sun has already regained its prominence. I’m on the Westbound Piccadilly line wearing a Cancer Research UK t-shirt that reads, “I’m a researcher fighting cancer”, and I can’t tell whether I’m getting more looks than is usual on the Tube. I alight at South Kensington to meet a friend of mine, the bubbleologist Li Shen. (And yes, that is now a technical term. Li, who has a degree in mathematics, is a PhD student studying the physics of bubbles, which has far-reaching implications: from the amount of bubbles generated by different types of beer to the undesired foaming of lubricants used in oil extraction.) But we’re not just here to catch up, although it is conveniently close to his lab/office at Imperial College. No, we’re here to join the March for Science. [All of the following images were taken either by Li or by me.]

science march banner.jpg

According to the BBC, “thousands of people” joined the march, the first of its kind taking place on the annual Earth Day and organised around the world. I think the event probably got part of its boost from the Women’s Marches that took place on January 21st, the day after Donald Trump’s inauguration. Certainly, the protesters on both occasions had much in common.

destroy the patriarchy, not the planet

One of the most notable differences between the two events, however, was that this second protest was certainly smaller and also much quieter. I suppose it’s true that scientists – and yes, the marchers were mainly scientists and their relatives, partners and close friends – are a little bit shy and socially awkward. Amongst the stewards, one was trying to get the following chant off the ground, with little success, “Scientists are good at generating questions, not so good at slogans”…

french embassy

Here’s a blurry Li in the foreground, with a sharp French embassy in the background. Walking by I couldn’t help but send what’s known as a “Stoßgebet” in German to the high heavens; roughly translates as a quick (secular) prayer. For now we can breathe a brief sigh of relief after the first round of the presidential elections. Hopefully Europe, science and European Research Council funding will be able to continue to prosper.

knowledge trumps ignorance

Speaking of Trump, the March for Science event emanated from Washington DC, where it started as a protest against fake news, alternative facts and a world in which experts are regarded as worthy of derision. Honestly, as with the Women’s March, I don’t know and can’t tell how much impact marches like these actually have in politics, but as a start there was significant media coverage. Even Buzzfeed compiled its list of top banners and slogans (some scientists do have a sense of humour). My personal favourite was this one, of course.

big brains

I do know that within three months I went to two marches, the first two of my life. Ideally, I won’t have to go to any more and will be able to spend my Saturdays in the lab, where a diligent PhD student should be (and where I know some of my colleagues were). Lastly, let’s give reason, described by Wikipedia as being “the capacity for consciously making sense of things, applying logic, establishing and verifying facts, and changing or justifying practices, institutions, and beliefs based on new or existing information”, a big thumbs up.


Behrens lab retreat 2016

Imagine spending a weekend in these idyllic surroundings in the Peak District with nothing to do but talk about and discuss science.


The Peak Mermaid Inn – taken at sunrise on November 13th 2016

Well, that’s exactly what we, the Behrens lab, did last weekend. We invited a keynote speaker, Roland Rad, and Dieter Saur’s group from the Technical University of Munich to join us. Each of us gave a talk about the most interesting or exciting aspects of our projects and in between we drank copious amounts of coffee. In the evenings we cooked enough food to feed a small regiment, drank beer, played pool, darts or table football, all punctuated by heated debates about science. Although this wasn’t a relaxing weekend by normal standards, it was motivating and inspiring and a good reminder of why I enjoy being a scientist: a combination of rational and logical thinking, curiosity and the drive to learn new things for their own sake, all shared with people who, by and large, know more than I do and think differently.

Of the talks I just want to highlight one in particular, because my project also uses one of the techniques mentioned. Dieter Saur is a medical doctor and has his own lab group, which studies mainly gastrointestinal diseases, including pancreatic cancer. In a recently published paper (Schönhuber et al, 2014) they describe an experimental system in mice called the “dual recombinase system“. This is a genetic system that allows the study of complex diseases such as cancer. Until recently it was only possible to simultaneously switch on a gene that drives tumour progression and switch off a gene that prevents tumour formation in a cell type or organ of interest (e.g. in the pancreas). Using the dual recombinase system it is possible to make genetic alterations sequentially. For example, in the beginning of a mouse’s development one can activate a potent tumour driver called Ras and delete an important tumour suppressor called p53. And then, once a tumour has formed, one can additionally delete genes that may be important to maintain the established tumour. Alternatively, the dual system also makes it possible to make genetic changes to the normal cells surrounding the (pancreatic) tumour. If all goes well then I will be able to use these tools to conduct experiments like this in the next year or so.

15044797_10154563370871405_2126581266_o zip-line

Oh and admittedly we did have an activity scheduled that was slightly less scientific: we got all geared up and went on a GoApe outing. Secured by a harness and after some rigorous safety instructions we got to fly down zip lines, balance over gaping abysses and jump over the void below.

Lastly, the following week saw Queen Mary University London and Barts host the 11th UK cancer stem cell symposium. There were several interesting talks, including by group leaders at the Crick Institute, but the most unusual talk was given by a philosopher called Lucie Laplane. She did her PhD in philosophy and combined this with a research master’s in stem cell biology. Putting the two fields together she came up with a classification of (cancer) stem cells using definitions and guidelines borrowed from philosophy, applied to biology. [In general, researchers agree that stem cells are cells that can self-renew (i.e. generate new copies of themselves) and can produce differentiated/specialised daughter cells.] The most important point was how to pin down what kind of characteristic “stemness” is or what makes a stem cell a stem cell:


Framework for defining (cancer) stem cells – copied from Lucie Laplane’s talk at the symposium

For instance, in some cases a stem cell might always be a stem cell no matter what the environment is like (i.e. categorical); other stem cells may be dispositional in nature, meaning that they always have the potential to act as a stem cell but only do so in a permissive environment. Alternatively, being a stem cell might not be property of a single cell at all but rather an attribute of an entire organ (i.e. systemic). Laplane argued that the way we define (cancer) stem cells has a huge impact on how we try to treat diseases such as cancer. For example, if cancer stem cells are “systemic” then even the best therapies targeted against these cells will fail because the system/the tumour will make new cancer stem cells from other tumour cells. Hans Clevers, one of the Gods in the stem cell field, wrote a glowing review of the book here.


Laplane, Lucie. Cancer Stem Cells: Philosophy and Therapies. Harvard University Press, 2016.

Schonhuber N, Seidler B, Schuck K, Veltkamp C, Schachtler C, Zukowska M, Eser S, Feyerabend TB, Paul MC, Eser P, Klein S, Lowy AM, Banerjee R, Yang F, Lee C-L, Moding EJ, Kirsch DG, Scheideler A, Alessi DR, Varela I, Bradley A, Kind A, Schnieke AE, Rodewald H-R, Rad R, Schmid RM, Schneider G, Saur D (2014) A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer. Nat Med 20: 1340-1347

The #IceBucketChallenge Two Years On

August two years ago saw our facebook feeds flooded with footage of friends and acquaintances dousing themselves in ice-cold water to raise awareness and money for amyotrophic lateral sclerosis (ALS; or motor neuron disease (MND)) charities. It was the topic of the inaugural blog post and a follow-up one year later. My inherently slightly cynical and skeptical nature questioned whether all this social media craze (and £87.7 million raised) would actually make a difference. Well, facebook came to the rescue and linked me to articles from the BBC and The Guardian alerting me to a paper published recently in Nature Genetics (Kenna et al., 2016).

The researchers contributing to this study work in eleven countries across the world. (Who ever thought science benefited from international collaboration? Am I still frustrated by Brexit? No, not at all…) Large proportions of the funding were provided by the National Institute of Health in the USA as well as  ALS and MND Associations in the USA and UK. Kenna et al. sequenced those parts of the genome that are actively expressed – a technique known as whole exome sequencing – in over 1000 familial/inherited ALS patients and over 7000 controls. Since sequencing technologies are becoming better and cheaper all the time, this is the less impressive part of the study. Next, all this data was processed using so-called gene burden analyses. This is where I stop understanding what is done with the data, but in essence it was possible to use previously known genetic risk factors of ALS to infer overlooked genes that are also associated with the disease. In the figure below the genes indicated in blue are genes that were already known to confer ALS risk (e.g. SOD1 and FUS), whereas those in black are the new genes, and everything above the red dotted line was considered statistically significant.


Graph depicting genes associated with ALS risk – copied directly from Kenna et al., 2016

As you can see, the researchers identified mutations in the NEK1 gene through these sequencing and data analysis experiments. However, only about 10% of people with ALS have the familial/inherited form of the disease. Therefore Kenna et al. then went on to check whether these NEK1 mutations could also be found in samples from patients with sporadic ALS and indeed they could. Overall approximately 3% of ALS patients have abnormal NEK1 genes.

After all this data analysis the paper ends with a description of what the NEK1 protein normally does and what it might not be doing in ALS patients’ cells: NEK1 helps to repair damaged DNA and contributes to the formation of an organelle called the cilium. Now future experiments will have to focus on exactly why and how mutations in NEK1 contribute to ALS. And since only 3% of ALS patients have NEK1 mutations there are still many other genes to discover.

The Project MinE aims to do just that – with headquarters in the Netherlands, this collaborative DNA sequencing project is analysing samples from even more ALS patients and controls. Their website says that a donation of €75 enables sequencing and analysis of a single chromosome! Anyone fancy another cold shower?

Lastly, I’ve found an interesting article combining two of my favourite things (science and Impressionist art) – so look forward to that in the next post.


Kenna KP, van Doormaal PTC, Dekker AM, Ticozzi N, Kenna BJ, Diekstra FP, van Rheenen W, van Eijk KR, Jones AR, Keagle P, Shatunov A, Sproviero W, Smith BN, van Es MA, Topp SD, Kenna A, Miller JW, Fallini C, Tiloca C, McLaughlin RL et al. (2016) NEK1 variants confer susceptibility to amyotrophic lateral sclerosis. Nature Genetics advance online publication.