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.

reason

Cancer Research UK – PhD Student Meeting

Cancer Research UK (CRUK) is the world’s largest independent cancer charity (according to Wikipedia)  and funds thousands of scientists across the UK. In the latest annual report they state that more than £340 million were spent on research. Take a look at the fancy infographic here to see a break-down of how that money was spent:

annual report

The reason for writing this post on CRUK is that today the charity held its first-ever first year PhD students’ meeting in London, at the Quaker Friends House near Euston station. The attendees came from all over the UK: from as far afield as Aberdeen and Manchester to Oxford and Cambridge and finally us lazy Londoners who could afford to get up later than on a normal lab day.

The main aims of the meeting were to get to know some of the people working at CRUK’s head office in London and how, in future, we might apply for their funding. One of the first things I learnt today was that CRUK has made four cancer types – brain, lung, pancreatic (!) and oesophageal – “strategic priorities”, because the survival rates for these are still low and lagging behind those of, say, breast and prostate cancer. We also heard, from the senior research funding manager, Richard Oakley, how CRUK spends its money and what we can and are meant to do to help. Among other things this involves wearing branded t-shirts and participating in fundraising events. So tomorrow morning I will wear this to run in the park in preparation for the 10 km Race for Life happening at the end of June – please feel free to fund me and/or the maybe pink team and/or join the run! [We can start a separate conversation on the topic of the martial language used by CRUK, and other charities, to help raise the money. N.B. The back of the t-shirt reads, “Ask me about my life-saving research.”]

cruk

Since doing a PhD is all about the learning experience, most of the morning was filled with one of three workshops on either a) assertiveness, b) time management, or c) having an effective working relationship with your supervisor. I chose the first option, and although some people (especially in my lab) will argue that it would be better if I were a bit more quiet on occasion, I thought it would be interesting to see what it could offer. The basic message was, of course, quite clear: effectively communicate your needs whilst appreciating other people’s needs. Easier said than done for sure. The only thing that helps is practising being in potentially awkward situations and putting oneself outside one’s comfort zone, which is where learning can happen. Possibly the most helpful information was to realise what isn’t assertive behaviour (e.g. being too passive, or too (indirectly) aggressive) and making sure to recognise those behaviours in oneself and learning to avoid them in future. We’ll see how that goes.

Over lunch we got to browse a few posters. I particularly enjoyed the ones on intestinal stem cells and a potential preventative treatment for breast cancer using the diabetes drug Metformin. And lastly, we were politely, with the help of beer and/or wine, coerced into networking…

An Introduction to the Pancreas and its Cancer(s)

Given that the four-year PhD I am about to embark on is being partly funded by Cancer Research UK (CRUK), why not start with a short video they have put together containing ten things about that pancreatic cancer that you may (not) have known:

Firstly, is there anything more to its anatomy than “being a small organ in the abdomen”? Why yes, funny you should ask. The pancreas reaches up to 15 cm in length in humans and is a J-shaped structure, apparently a bit like a hockey stick. The organ is not symmetric, rather it is made of a head (left), body (middle) and tail (right), as shown below. In the head the main pancreatic duct merges with the common bile duct before they join into the duodenum, where food is further digested after it leaves the stomach.

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Cartoon illustration of a human pancreas – copied directly from Hezel et al, 2006

As is often the case in biology – and this applies from the level of individual proteins to a whole organism – there is an intricate relationship between structure and function. The pancreas has two main functions: firstly, it contains endocrine cells that produce hormones, such as insulin, to regulate glucose balance (or homeostasis). Secondly, it contains exocrine cells, which make up the majority of the organ, that produce enzymes to aid food digestion. These two categories of cells therefore work together and coordinate the body’s metabolic response to food consumption.

Not all animals have pancreases as complex as those found in mammals since they have evolved over time. Worms, for instance, have some specialised gut cells that produce a substance similar to insulin. Ancient sharks and some fish contain organs in which the exo- and endocrine cells are found together. Fruit flies astonishingly produce insulin in their brains and, in particular, those cells develop from a completely different tissue in the embryo – called the ectoderm – than in other animals, where the pancreas stems from the endoderm. In amphibians and mammals the anatomy becomes more complex with characteristic “islets” of endocrine cells. (See Stanger & Hebrok, 2013 for more details.)

Since I am the daughter of two doctors I am usually interested in the pathological side of human biology. What sort of diseases befall the pancreas? Possibly the first that comes to mind is (type I, auto-immune type) diabetes in which the pancreas fails to make enough insulin because the body is attacking its own beta cells that normally produce insulin. Other than that the pancreas can of course become inflamed like any other organ and this is known as pancreatitis. It is caused, among other things, by high doses of alcohol. Lastly, the pancreas can become cancerous.

Although there are a few different types of pancreatic cancer the focus will lie on pancreatic ductal adenocarcinoma (PDAC) since it is both the most frequent and also the best understood type. It is one of the deadliest types of cancer because it often goes unnoticed until the tumour has disseminated (or metastasised) in the body – fewer than 10% of people who are diagnosed survive for longer than five years.

Therefore it is important to find out more about PDAC. But for the moment there is a lot we do know, decades of hard work that are often frustratingly glossed over. For instance, the genetic mutations that start and maintain PDACs are well known. Among them are activating mutations in a famous oncogene – a gene whose overactivation contributes to cell proliferation and cancer – called KRAS, and deletions of tumour suppressors – those genes/proteins that act as checks and balances and stop cells from overproliferating – such as p16 and p53. Moreover, it is well known when these mutations occur during the development of the cancer. The following image shows how some PDACs form: from healthy tissue to slightly abnormal tissue until it invades into the rest of the body.

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Histology of normal (left), dysplastic (middle) and malignant (right) pancreatic tissue – copied directly from Bardeesy & DePinho, 2002

As for treatment, the most effective method, if successful, is surgery. However, this often involves removing the head of the pancreas as well as parts of the duodenum and this, in turn, means that the stomach has to be surgically joined directly to subsequent parts of the digestive tract, making it a complex procedure. In addition, patients receive radio- and/or chemotherapy, which “targets” most proliferating cells. Targeted therapies that are specific to the cancer cells, as opposed to healthily dividing cells, are, as far as I am aware, not particularly established yet for pancreatic cancer.

For surgery to be effective the cancer needs to be detected at earlier stages. In other words, better diagnosis procedures need to be developed. Recently, two papers attracted some attention because they uncovered methods that could potentially make diagnoses easier using either blood (Melo et al, 2015) or urine (Radon et al, 2015) samples. However, as CRUK rightly point out, these techniques need to be refined for them to be able to tell true cancers from chronic pancreas infections.

And on that cheery note… Next time you can look forward to learning a bit more about how PDAC is studied in the lab and pancreatic anatomy in slightly more detail.

References:

Bardeesy N, DePinho RA (2002) Pancreatic cancer biology and genetics. Nat Rev Cancer 2: 897-909

Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, DePinho RA (2006) Genetics and biology of pancreatic ductal adenocarcinoma. Genes & Development 20: 1218-1249

Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, LeBleu VS, Mittendorf EA, Weitz J, Rahbari N, Reissfelder C, Pilarsky C, Fraga MF, Piwnica-Worms D, Kalluri R (2015) Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 523: 177-182

Radon TP, Massat NJ, Jones R, Alrawashdeh W, Dumartin L, Ennis D, Duffy SW, Kocher HM, Pereira SP, Guarner  L, Murta-Nascimento C, Real FX, Malats N, Neoptolemos J, Costello E, Greenhalf W, Lemoine NR, Crnogorac-Jurcevic T (2015) Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma. Clinical Cancer Research 21: 3512-3521

Stanger BZ, Hebrok M (2013) Control of Cell Identity in Pancreas Development and Regeneration. Gastroenterology 144: 1170-1179

A Fledgling PhD Student

Here I am standing in front of the gigantic Francis Crick Institute in London, which is situated right next to St. Pancras railway station and just behind the British Library. I’m not actually saluting, just shielding my eyes from the sun. [Photo courtesy: Kai Wang]

P1100140

As you can see, even a wide-angle lens cannot quite capture all of the building in a single shot. A recent News article in Nature described the institute as “Sir Paul’s Cathedral”. It will be the biggest biomedical research centre in Europe – it’s bigger than Buckingham Palace – and will become populated with scientists early next year. The building costs came to a whopping £700 million. Additionally, its annual budget will be £150 million, which is more than the School of Biological Sciences at the University of Cambridge received in the academic year 2013/14 according to this report (if I am interpreting it correctly). The charity Cancer Research UK (CRUK) is one of the Crick’s main funders and this summer they are launching an art campaign to raise money for the Crick: CRUK is setting up 21 DNA sculptures across London so that you can go on a DNAtrail and at the end of the exhibit the “sculptures will be auctioned in September 2015 to raise funds to help complete the construction of the Francis Crick Institute”. Makes it sound slightly like they won’t be able to complete the building unless the auction goes really well… As far as I’m aware the Crick already has a roof and is currently being furnished. [Picture copied from the CRUK website.]

dna_trail_02

Sir Paul Nurse’s “Crick project” was/is daring and the numbers above are certainly impressive. But with this grandeur come great expectations. Sceptics of the project will be awaiting great results, results even better (and by that I probably mean more translatable into medicine and the real world) than those already being produced by the research groups moving into the Crick. Although I have no doubt that it will be an exciting place to work, with excellent facilities and support staff, I can imagine it will also be a high pressure environment. We shall see.

At the moment it’s barely been a week since I graduated with my undergraduate degree (woohoooo!) and part of my brain is already getting a little bit impatient for something new to think about and to work on. Another, perhaps more calculating, part of my brain is saying, “Are you mad? Enjoy these weeks of freedom. You’ll never have holidays like these again!” In any case, the PhD doesn’t start until September but in the mean time I’m scheduled to join a lab meeting of my future lab in late July. That means that I should do a bit of preparatory reading beforehand, including the lab’s most recent publications (see below).

References:

Behrens A, van Deursen JM, Rudolph KL, Schumacher B (2014) Impact of genomic damage and ageing on stem cell function. Nature Cell Biology 16: 201-207

Chakraborty A, Diefenbacher ME, Mylona A, Kassel O, Behrens A (2015) The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling. Nat Commun 6: 6782

Diefenbacher ME, Chakraborty A, Blake SM, Mitter R, Popov N, Eilers M, Behrens A (2015) Usp28 Counteracts Fbw7 in Intestinal Homeostasis and Cancer. Cancer Research 75: 1181-1186

Sancho R, Gruber R, Gu G, Behrens A (2014) Loss of Fbw7 reprograms adult pancreatic ductal cells into alpha, delta, and beta cells. Cell Stem Cell 15: 139-153

Sancho R, Cremona CA, Behrens A (2015) Stem cell and progenitor fate in the mammalian intestine: Notch and lateral inhibition in homeostasis and disease. EMBO Reports 16: 571-581

Schulein-Volk C, Wolf E, Zhu J, Xu W, Taranets L, Hellmann A, Janicke LA, Diefenbacher ME, Behrens A, Eilers M, Popov N (2014) Dual regulation of Fbw7 function and oncogenic transformation by Usp28. Cell Rep 9: 1099-1109

PhD Interview for the Francis Crick Institute!

Despite being funded as a Cancer Research UK charity, the London Research Institute (LRI) went to considerable lengths to ensure that we interviewees were comfortable during our three-day visit to London and the institute. Firstly, our travel expenses – ranging from short intra-England train journeys to flights from across Europe and North America – were covered, as well as our accommodation at a hotel overlooking Russell Square at the heart of Bloomsbury:

image1

The first day was probably the most strenuous. First we listened to introductory talks given by the LRI Academic Director and the LRI’s Deputy Director who, incidentally, also quoted Donald Rumsfeld about the unknown unknowns just like at the departmental research day. Furthermore, as part of my destressing strategy I took a walk around the area during one of the breaks, inevitably stumbled into a bookshop and found this:

image2

The rest of the first day was filled by talks given by each of the recruiting group leaders. Eighteen times ten minutes of concentration. After that we got the chance to speak to those principal investigators (PIs) we were interested in. Lastly, we had dinner with the PIs and some of their students. And although all of this was not part of the “official” assessment procedure I think it was important to be making a good impression throughout, and therefore by the end of this first day most of us felt exhausted.

The official panel interviews were scheduled for the second day. We each had to give a presentation of a research project we were involved in, as well as a critique of a research paper. We were then asked some questions on these presentations and also had the usual questions hurtled at us, “Why do you want to do a PhD? Why do you want to do it at the LRI? What are your long-term goals?” Etc.

We were also privy to a tour of the LRI building at Lincoln’s Inn Fields. During the introductory talks they emphasised how great the facilities – DNA sequencing, flow cytometry and microscopy among others – at the LRI are. I was skeptical at first, but the tour was convincing, especially considering that probably not so much money is being invested in the upkeep of this building due to the move of the LRI into the Francis Crick Institute in 2016. At the Crick of course everything will be even better, as they didn’t fail to mention at every possible opportunity.

On the second day we had dinner together with the lab members of the recruiting labs, but without the PIs who were busy trying to work out who to invite for the third day on which one-on-one interviews would be held. We were certainly more relaxed this evening. However, the next morning between 7.15 and 8.00 am we had to come down into the reception area of the hotel to pick up a letter informing us whether we had been invited for the third and final day. It was irrational to be nervous because at this stage there was absolutely nothing to be done about the situation. Nevertheless, I, and probably many others, had difficulty sleeping that night.

Luckily, I was invited back to speak to three group leaders: Axel Behrens, Victoria Sanz-Moreno with Ilaria Malanchi, and Caroline Hill. In these sessions it became clear that I would want to work either with Axel on pancreatic cancer or with Victoria and Ilaria on melanoma. The third project was more focussed on neurodevelopment, which is interesting but my gut feeling told me to veer away from it simply because I have a stronger background in cancer biology.

At the end of the third day we had to hand in a preference list, and then all there was left to do was to go back to Cambridge and wait. But the waiting was mainly a formality since it had become clear during the day that Axel Behrens’ lab was going to make me an offer I couldn’t refuse. I am extremely excited! London, here I come!