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

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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).

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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).

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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.

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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!

 

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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.

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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.

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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:

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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.

References:

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

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!