The halfway mark

A few days ago someone called me a “senior PhD student”. And I know it’s true. I’m just over two years, or halfway, through the official funding length of my PhD. “Official” because a lot of students in my lab end up staying for longer to publish a paper, or sometimes two. So I thought it would be a good time to take stock, take a moment to re-evaluate my life choices while trying not to fall into that abyss labelled “existential crisis”.

First, let me say this: doing a PhD is hard. Harder than you imagine it will be, even after countless people have told you that it will be challenging or difficult. It’s hard in ways I hadn’t foreseen. It tries my patience – with people, with inanimate objects, with biology itself – on a daily basis. It makes me do tasks I don’t particularly enjoy (e.g. repetitive pipetting) but that need to be done in order to accomplish those I do. (I realise that this applies to a lot of different jobs.) At the same time, especially on an intellectual level, I find it less challenging, less stimulating than I had expected or hoped for. A lot of time and energy are used to concentrate on practicalities, which leaves less of the brain’s random access memory for really thinking about science.

But it’s not only frustrating, not only bad. I have learnt a lot in the last two years. Practical skills in the lab, of course, including how to clean up centrifuges after almost breaking them, how to plan and execute experiments that take days if not weeks to complete, how to always set up experiments whose results can neatly be presented in figures, including using all the proper controls. Doing a PhD is also teaching me how to deal with the feeling of not having finished or completed something (the work never ends) as well as juggling the (natural?) highs and lows, the alternating sensations of shining confidence and utter dejection, that accompany work. [I’m pretty sure the levels of emotion elicited by work are more extreme than those caused by hormones.] Oh and then of course all the new theoretical knowledge in the forms of attending talks and conferences, as well as reading papers. Isn’t it pretty cool, for example, that using a modified version of CRISPR/Cas9 it’s now possible to precisely edit certain DNA base pairs (rather than making a cut in the DNA and hoping for the best; Gaudelli et al, 2017)? Or that reading about cancer stem cells during my degree has turned into me actually doing some of those types experiments?

Another thing that takes getting used to is that progress is slow. Improvement and success can’t simply be measured by essay feedback and exam results. It takes more effort to see and appreciate how far we, as PhD students, have come from our even humbler beginnings as school and university students. As proof of this let me show you the evolution of a scientist:

science evolution

Above: At the summer science camp of the Vienna Open Lab; Below: As a PhD student at The Francis Crick Institute

In addition to acquiring a better haircut I’ve also increased my skills when it comes to processing and taking immunofluorescence images on a fancy microscope. The Zeiss software installed on our microscopes is called Zen, which is ironic when I lose my cool after it crashes repeatedly. (The software we use to acquire data on our flow cytometers is called Diva, which is much more apt.)

IF evolution

Above: a mouse embryonic fibroblast, taken with lots of help at the MFPL in Vienna; Below: Zen screenshot of mouse pancreatic cancer tissue, taken at The Crick

The halfway mark also coincides with considerable change in our lab: several senior PhD students and post-docs are leaving for other positions (academic or as MBA students) and there are two new PhD students, one of whom is also a clinical fellow (who happens to read the London Review of Books!). This makes me one of the more seasoned members of the lab and I think it’s a good opportunity to make sure I take more responsibility, try to be more innovative, as well as being generous with my time to help others, as others were when I started.

There are several things I will focus on in the near future to make sure I don’t lose motivation: attending more conferences (such as the international PhD student cancer conference in Berlin earlier this year); focussing on one avenue of my research project more and more, really going to the depth of one small problem; going to more lectures; making more time to think; reminding myself regularly of the progress I’ve already made.


Gaudelli NM, Komor AC, Rees HA, Packer MS, Badran AH, Bryson DI, Liu DR (2017) Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature advance online publication


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.


First PhD Checkpoint

In December, we – the (mostly) young and innocent first-year PhD students at the Francis Crick Institute – gave our first formal talks. Each student had to present the outline of their project to all the other students in a ten minute slot. This was probably intended mostly for our own benefit to ensure that we had at least a rough idea of what we will be working on for the foreseeable future. Here I’d just like to mention a few of the talks that I found particularly interesting, but it’s worth saying that I thought the overall level of presentations was very high and the questions we ended up asking each other were well thought through. Overall a very enjoyable experience.

  1. To begin with there were a couple of talks from students in the same lab studying the interactions of cancerous cells with the immune system. In particular, they are trying to find out how dendritic cells – cells that normally alert effector cells of the immune system that something is wrong (e.g. an infection is happening) – can sense the presence of dead/dying tumour cells and relay this information to so-called T cells. The two students are looking at both the molecular mechanism by which this happens, but also whether precursors of dendritic cells in the bone marrow have similar abilities.

  2. A few students in the programme are working on mathematical/computational projects and will never have to wear a lab coat. For example, one lab is interested in understanding how non-cancerous cells near a tumour interact with the cancer cells and influence their ability to move. To do this one can mathematically model the movement patterns of the “cancer-associated fibroblasts” and how they interact with extracellular proteins to form tracks for the cancer cells to move along. In the simplest terms (and that’s the only level at which I understand this), the model relies on the Morse potential, which is normally used to understand how atoms interact but can be scaled up to model interacting cells. Here is a video of a fibroblast interacting with a breast cancer cell; the accompanying text is maybe overly simplistic, but you get the gist:

    Another student is studying how sheets of cells move together, both during embryonic development and tumour formation. This relies (roughly) on modelling cells as polygonal shapes that stick together via their vertices. Yet another “dry” project is investigating how cancers evolve over their lifetime: this is done by collecting DNA sequencing data from cancer cells at various stages of their development and inferring which changes happened when.

  3. Since it is generally the metastases that are the deadly part of cancers it is important to  understand how cells move. There is, of course, a lot of information about this already but here the aim is to find out more about how different cancer cells (e.g. breast cancer and skin cancer) share certain features in their movement patterns.

  4. Not all labs in the institute study cancer. Some labs focus on basic research using yeast as a model organism. Both yeast cells and our cells contain a lot of DNA that is not translated into protein; for a long time all this DNA was termed “junk” and nobody bothered with it too much. It is becoming increasingly clear that this so-called non-coding DNA can still play various roles in the cell and some of these may be deleterious. Therefore one student is studying how cells prevent the activation (transcription) of some of these stretches of DNA.

  5. Another major branch of the institute deals with infectious diseases and the immune system more broadly. Two talks that I enjoyed on this front were given by students again working in the same lab. They are studying “neutrophil extracellular traps” (NETs), which I had never heard of before and sound quite cool. Neutrophils are a cell type of the immune system and are the first to react to infectious agents. By releasing very broad-acting antimicrobials they try to quell an infection in its infancy, but by doing so they also cause the four main symptoms of inflammation: pain, heat, redness and swelling. NETs are made of DNA and proteins from the neutrophils and are sticky. One of the students is looking into how NETs can exacerbate atherosclerosis, while the other is finding out how NETs physically trap invaders, such as the fungus Candida albicans.

  6. Lastly, and because it would pain me not to mention CRISPR, one student is trying to find a way to control the sex ratio of offspring in laboratory animals, specifically mice. While at first glance this might seem dangerous or cruel, it is actually part of an effort to reduce, replace and refine the use of animals in research. For example, if you are studying prostate cancer or ovarian cancer half of the experimental animals born are completely useless and end up being “wasted”. At the moment, some agriculture relies on physically sorting sperm cells into those carrying X or Y chromosomes and using mainly those with X chromosomes for in vitro fertilisation (because far fewer male animals are needed). Although this is a very accurate method it is expensive and time-consuming. Since CRISPR is precise and can be genetically encoded it would virtually work by itself once established.

This is by no means an exhaustive list of the topics covered by our projects, but hopefully it’s an interesting glimpse into what we are currently spending (almost all?) of our brains and energy trying to figure out.

These talks will be complemented with a so-called thesis committee meeting later this month: here each student will present a very similar talk to three professors or group leaders, who will be advising the project from an outside perspective. Hopefully being locked in with three clever and knowledgeable people will conjure up constructive criticism as well as (even more) new ideas!