The Joys of Revision #2

Exams are drawing closer and that is both a relief – at this point I really just want to be done with this taking exams business – and a consternation – they do seem to spring up on one every year rather unpleasantly and seemingly out of the blue. To deal with my mix of boredom and quiet anxiety it has been useful to seek out various different places to do revision. A friend of mine even has a blog dedicated to describing several Cambridge libraries.

To begin with there is of course my “home” library at Pembroke College. Large desks and sitting between volumes of classics (Greek, Latin, English, you name it) make for a good working environment. However, the bell in the clock tower, which strikes every half hour, is a rather unpleasant reminder of how quickly time is ticking. [Photo copied from the Pembroke College website.]

Library-Photo-resized

Just across the street is the Colman Library, the library of the Department of Biochemistry. Again this is quite an old building with large wooden desks or smaller, personal booths to sit at. It is rarely busy, often giving it a feeling of calm, but the people who do study there are often my (stressed?) colleagues, which could become a bit unpleasant the closer we get to exams.

If one is feeling particularly brave as a science student one can make one’s way to the Sidgwick site where several art/humanities and social science departments are situated. The main recollection I have of the law library is its coldness (temperature-wise). In the economics library people were generally better dressed, although I hear that this is also deteriorating as  exams approach. The Judge business school has an “information service” instead of a formal library, in which people can chat and bring in drinks, which makes for a more relaxed atmosphere, but when I heard some students (?) talking about their newest great idea in which they’ll move from the production to the service sector to make “massive profits” I started feeling out of place.

The winner of the library competition is undoubtedly the Faculty of Education: it’s bright and full of light wood, the staff are helpful and kind (there was free cake on Friday afternoon) and one can sit looking out onto a green garden. [Photo copied from their website.]

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The Joys of Revision #1

Please immediately note the hint of sarcasm in this title. What academic year would be complete without the harrowing prospect of end-of-year exams, which, this year, happen to also be finals? … Well, exactly. Any old academic year would be fine without. But alas, that is not how the system works. So on top of being judged on the basis of our lab project/dissertation/viva voce examination we also need to take two written exams, which are worth 50% of our mark.

To ease the transition from dissertation writing and editing into revision I thought I would start with something fun/potentially useless that can be classed as elaborate procrastination:

Landmark timeline

As mentioned previously, some of our teaching was provided in the format of seminars discussing landmark papers – papers that have shaped the way biologists think about their areas of research and that have had lasting, even if sometimes subconscious, effects. Several of the professors emphasised the importance of understanding these papers within their historical contexts, which is, I would contest, not something we scientists normally think about. Therefore I decided to look for a tool that would allow easy creation of a timeline like the one shown above and the only free app I could find in the store is simply called Timeline 3D. Right, well, and I just realised that on top of procrastinating by colour-coding different landmark papers I’ve now also spent a good fifteen minutes writing this blog post. If anyone else has well-disguised procrastination tools, please do share…

P.S.: Another way to pretend like you’re doing something useful – attend the departmental seminar given by a Nobel prize laureate, Jules Hoffmann. I was pleased to hear that he was appreciative of all of his collaborators and acknowledged his students and post-docs; something he seems to share with another Nobel prize winner, Christiane Nüsslein-Volhard, who gave a seminar a few weeks ago. Based on these examples I was about to draw the conclusion that a couple of the marks of great scientists are a) their willingness to acknowledge co-workers and b) to some extent their modesty (granted, this one doesn’t apply to other Nobel laureates I’ve encountered [e.g. James Watson]). However, as I was reading about Jules Hoffmann I very quickly came across this blog written by Bruno Lemaitre, a former research associate in Hoffmann’s lab, claiming that most, if not all, the award-winning work was conducted by him without encouragement/help from Hoffmann. Now what to believe?!

A Science Masterclass

For the past three days I have been acting as a so-called student ambassador during an Easter residential science masterclass. This was a programme aimed at 14- to 16-year old students (about to take their GCSE exams) from across several areas of England, including Bedfordshire, Leicestershire, Northamptonshire and Southwark (London); the students stayed in Pembroke College accommodation for two nights and participated in a range of scientific activities. The students from these “link areas” were nominated by their teachers and attend schools that may not have particularly strong connections with any universities, and Oxbridge in particular. The idea of these Access and outreach programmes is to encourage students from less privileged backgrounds to consider applying to university, including Cambridge. In part this is achieved by showing them that Cambridge is not only for posh, rich, upper-class students (although they do also exist).

We started the masterclass with a tour of Pembroke College – did you know that the college was founded in 1347, but did not admit women as members until 1983? Or that one of our most famous graduates, William Pitt the Younger, became Prime Minister at the age of 24? Or that there are 116 libraries scattered around Cambridge?

Next, there was a treasure trail through the historic city centre – although “treasure” might have been a misnomer depending on your inclinations, since each station consisted of working through a maths problem. We saw Newton’s apple tree outside Trinity College and The Eagle pub, where Francis Crick and James Watson allegedly had the insight into “the secret of life”, the structure of DNA. [We discussed the contribution of Rosalind Franklin, of course!] Dotted in between all these activities were various brainteasers, such as trying to solve the Monty Hall problem or Einstein’s puzzle (have a go – they are surprisingly fun).

In addition to the activities organised by the college’s school liaison officer there were outings to various University departments: we examined the relationship between leaf surface area and volume in both desert and tropical plants at the Botanic Gardens; we compared femur length and diameter in dinosaurs of varying sizes at the Sedgwick Museum of Earth Sciences and came to the conclusion that there is a natural limit to the size of land animals, since at some point their femurs would have to become wider than they are long to support their weight. And as if that was not already enough science for a day we walked to the Cavendish laboratory, where I attended my first ever physics lecture:

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The day was rounded off by a talk on higher education, a formal dinner (juice instead of wine) and an evening with Sir Isaac Newton. However, the most striking point was really that the English secondary school education system can be extremely restrictive: if you want to apply for a science degree at university then essentially you have to take only science A levels; a girl asked about whether she could combine science and drama, but essentially she was advised against it and that was a slightly heartbreaking moment. On the other hand, choosing only science subjects means you can focus more and maybe gain a deeper understanding of those few subjects, but should that really happen at the expense of other interests? And at such an early age?

In any case, our last big activity took us to the plant sciences department where we extracted chloroplasts from lettuce leaves, measured their sizes and investigated whether a certain herbicide can inhibit photosynthesis – it was fun to teach them how to use a Gilson pipette (known as an Eppendorf pipette in German-speaking Europe) despite being slightly shocked by the fact that some people do not already know how to use them…

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Overall, the students on the programme were really a pleasure to supervise – asked interesting questions, engaged with my questions, had a good sense of humour – and made my first teaching experience both exhausting (in a good way) and enjoyable.

Departmental Research Day & M. Sci. Symposium

The beginning of Lent term was far from gentle. For three days I have been sitting in lecture theatres and seminar rooms. Firstly, for a full day we listened to several professors/group leaders of the biochemistry department describing their research. And secondly, we had two days of the so-called Part III symposium, that is a twenty-minute research update from each of the 31 biochemistry M. Sci. students in the department. (Since then I have started working in a lab again and I have to admit I had forgotten how strenuous it can be.)

First things first. The “departmental research day” was hosted at Robinson College, because the lecture theatre within the department is actually too small to seat all the members of staff and students. The introduction was given by Chris Smith and his most interesting point was probably that the department received an Athena SWAN bronze award last year, which “recognises and celebrates good practice in recruiting, retaining and promoting women in Science, Technology, Engineering, Mathematics and Medicine (STEMM) within Higher Education”. So three cheers for the department!

AthenaSWANBronezAward

The actual research talks by the various professors ranged from mildly piquing to downright riveting. There were several talks on cancer (the head of the department, Gerard Evan, is a cancer biologist so this is hardly surprising): at one end for example, Helen Mott explained how basic biology, crystallography and peptide chemistry are being exploited to research a new class of drugs based on alpha-helical peptides, which are meant to block activity of some small GTPases (sometimes known as cellular switches because they can turn signalling pathways on and off). At the more clinical end, Kevin Brindle demonstrated how techniques such as dynamic nuclear polarisation magnetic resonance imaging (MRI) are progressing to better image biology/cancer in (live) patients. However, the department is also strong in the field of structural biology, since the crystallographer Tom Blundell used to be the head of the department. Furthermore, there is an increasing number of lab groups working on single-celled eukaryotes such as trypanosomes and Toxoplasma.

Additionally, there were at least two overt political references to keep us on our toes. The first one was this:

Screen Shot 2015-01-14 at 20.14.58And I have to say that I wholeheartedly agree. Perhaps unsurprisingly, the professor who used this image in her slides is originally from the Czech Republic and probably quite vehemently opposes the idea of having an in/out referendum in the UK. [Eukaryotes, by the way, are organisms whose cells contain a nucleus and would include plants, animals and fungi, but also single-celled eukaryotes such as trypanosomes and Toxoplasma.]

The second political reference was a quote by Donald Rumsfeld: “As we know, there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns – the ones we don’t know we don’t know.” He said this in response to questions about Iraq’s involvement in the supply of weapons to terrorist groups. In the context of science this was a comment on the inherent difficulties of modelling biological processes: Steve Oliver uses yeast as a model organism to study metabolic pathways, and in contrast to the qualitative modelling I have been doing, his models are quantitative (i.e. use differential equations and enzyme kinetic data). Interestingly however, both types of model can suffer from similar problems; for example they can be plain wrong, or incomplete, or based on faulty assumptions. And sometimes when we know they are wrong that doesn’t mean we know how to improve them. Not knowing that they are wrong/incomplete (i.e. the unknown unknown) is arguably the most comfortable position to be in.

The following two days were filled with project reports of all the biochemistry M. Sci. students. It is worth noting that several of these talks were possibly more interesting and of better quality than some of those given by the professors. There was an extremely wide variety of topics including: cancer research, developmental biology, disease biology (including the rare lysosomal storage disease called Krabbe disease), in vitro enzyme evolution, structural biology (including taking trips to the x-ray source near Oxford, the Diamond Light Source), stem cell biology and research into the origins of life. This latter research project is investigating how the first RNA molecules may have come together to form larger, catalytic molecules of RNA (“RNA world hypothesis”), and to do this the reactions are carried out at -9ºC in the eutectic phase of water-ice, a condition thought to mimic prebiotic chemistry.

Lastly, what would a blog post be without the mention of CRISPR. At least two of the M. Sci. projects involve the use of this genome-editing technology. In one case it will be used to knock-out a microRNA that may be involved in the regulation of bicoid mRNA during Drosophila (fruit fly) development. And in the other case it is being used to target a transcription factor that is implicated in the regulation of stem cell fate. Interestingly, the strategy here involves using two guide RNAs simultaneously, both targeted to within the gene of interest, with the aim of creating a large deletion rather than just a small insertion/deletion.

Needless to say, the progress of all our projects is far slower than we (and probably our supervisors) would have hoped.

Michaelmas Term Round-Up

This past Michaelmas term – the first term at several British universities including Cambridge and Oxford, which runs between late September/early October to Christmas – was an exceedingly exciting time.

The master’s thesis project I am working on progressed from being an unmanageably complex undertaking to a concise and interesting project. At this stage, the melanoma model I have constructed includes not only the most basic cellular phenotypes (e.g. proliferation and cell death) as readouts, but also an indication of motility/metastatic potential. This addition seemed important to us, because in the case of melanoma the metastases cause mortality. The model accurately recapitulates a range of data from the available literature and can now be used to make simple predictions about the phenotypic readouts when the starting conditions are altered. Next term (Lent term here in Cambridge, but Hilary term in Oxford) I will actually get to test some of these new hypotheses in the lab. For example, I will be carrying out immunohistochemistry staining of tumour samples from mice with genetically different melanoma lesions and checking whether the differential activity of various signalling pathways predicted by the model actually occurs in vivo. Additionally, we will perform analyses on a cell line (from Girotti et al. (2013)) that has become resistant to vemurafenib (the drug described here) and try to confirm the mechanism(s) of resistance as predicted by the model.

Apart from the project the biochemistry course also consists of taught elements, including lectures and weekly workshops. The lecture module I took was entitled “cell fate”; we learnt about stem cells, somatic cell reprogramming, neurodegenerative disorders and cellular ageing and cell death. I’m not sure what this says about me, but one of the things I look forward to most during the upcoming holidays is being able to sit down with a cup of tea and (re)consolidate the content of these lectures, and also tackle some essay questions, such as, “Is it accurate to describe embryonic stem cells as stem cells? In what ways do they differ from adult stem cells?”

Interestingly, I think the combination of starting to use Twitter, blogging and learning more and more about the latest experiments and scientific discoveries in a particular area has made me much more aware of the current scientific literature. A particularly helpful resource is the Nature News & Views section, which provides short commentary articles from where one can follow up by reading the actual papers. For example, just a couple of days ago this led me to read about a new type of pluripotent stem cell (Tonge et al. (2014)) termed the F-class cell (F stands for “fuzzy” because of their morphological appearance). The authors conducted various experiments, including in vitro differentiation tests and teratoma formation assays, to show that the F cells truly are pluripotent. On the one hand, unlike embryonic stem cells (ESCs), they cannot form part of a chimaeric embryo when injected into the blastocyst (early stage of embryo developments). On the other hand, however, due to their morphology and decreased adherence to each other and the Petri dish they may be more suited to being grown in stirred suspension culture. And this may be useful for the testing of new drugs or in clinical applications which require reprogramming of large quantities of patients’ somatic cells. (This might be an interesting development worth mentioning in the essay I will write once I stop procrastinating by blogging.) Tonge et al. summarise their findings in this diagram (copied from the paper):

Screen Shot 2014-12-14 at 14.01.26

Lastly, this term also marked the beginning of the quest for a PhD position starting next year. Since the last update about this I have been offered a place to study type 2 diabetes at the MRC Clinical Sciences Centre! Another meeting with the supervisor in January will hopefully shed more light on the precise project to be undertaken and also help in the decision-making process.

All in all, despite (or maybe precisely because?) the differences between this term and the previous years here I feel like I’ve had a successful and worthwhile last Michaelmas.

References:

Girotti MR, Pedersen M, Sanchez-Laorden B, Viros A, Turajlic S, Niculescu-Duvaz D, Zambon A, Sinclair J, Hayes A, Gore M, Lorigan P, Springer C, Larkin J, Jorgensen C, Marais R (2013) Inhibiting EGF Receptor or SRC Family Kinase Signaling Overcomes BRAF Inhibitor Resistance in Melanoma. Cancer Discovery 3: 158-167

Tonge PD, Corso AJ, Monetti C, Hussein SMI, Puri MC, Michael IP, Li M, Lee D-S, Mar JC, Cloonan N, Wood DL, Gauthier ME, Korn O, Clancy JL, Preiss T, Grimmond SM, Shin J-Y, Seo J-S, Wells CA, Rogers IM, Nagy A (2014) Divergent reprogramming routes lead to alternative stem-cell states. Nature 516: 192-197