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):
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.
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