Ralitsa’s pensieve of the last month: time-out to breathe

Back in my “young” days, I used to love Harry Potter, and there is one magical item that has been imprinted on my mind. It is Dumbledore’s pensieve. For the non-Harry Potter addicts among you, The Pensieve of Hogwarts is a magical instrument used to empty your head of memories as well as to go back and view them again. In the past month, a magical Pensieve is exactly what I have needed… Jumping head first into my first PhD year, full of excitement and new ideas, my brain is experiencing space limitations compounded by the scarcity of hours a normal day has to offer. It is time to tidy up my brain space a bit, so let my blog be my Hogwarts Pensieve. What’s happened in the past month – or rather what has not happened, and why does it feel like a whole year rather than a month?

Let this blog be my Hogwarts pensieve

The project manager: being organised is time-consuming, but it WILL pay off in the long run

As a PhD student, I have the privilege of being my own daily boss. I have to think, to gauge pros and cons of different approaches, to design new experiments, to synthesise unlimited new knowledge and TO PLAN smart. These skills develop along the way, through trial and error and through guidance offered by others, in particular my real boss – i.e. my supervisor – and more senior researchers in the lab.

Prior to starting in the lab, I submitted a PhD proposal to the Wellcome Trust, outlining the main aspects of my research plans for the next three years and importantly, how I would manage my data. Data management has become a hot topic in science as several problems of poor data storage have emerged in recent years, preventing access and use of the data for replication purposes. I find this amusing Youtube video (involving little bears) particularly useful to watch if you want a quick introduction to the importance of data management. As a result, I have sort of turned into a data management advocate in the lab, reporting back from various talks and courses on good data handling; for instance, my supervisor has now prompted everyone to include a slide at the end of their powerpoint presentation on how the data has been handled and stored. Ideally, if someone else wants to go back to your data 5 years from now and understand how you have got the results you have got, the data should provide enough meaning and content for that person to do so without having to track you down (chances are you don’t remember it anyway!).

Acquiring the “data management freak”-role has also meant that I must make sure I practice what I preach! So I have spent a considerable amount of time performing seemingly dull tasks like reading best practices in data handling, followed by the establishment of multiple spreadsheets to track down content relating to each individual project, the generation of readme.txt files enabling anyone to understand what a particular workbook or folder includes – and how the content was generated, as well as regular backing-up of all my data onto a centralised virtual drive AND a hard drive! Phew! It DOES take time to stay organised, but I am already benefiting from the ease with which I can track my procedures and all the reagents I have generated including WHERE they can be found. Not to mention the tower of boxes that is already building up inside my lab freezer – having codes (e.g. Box A1, A2 etc.) on the outside of each box as well as a spreadsheet listing all my current boxes and their contents makes it so much easier to pick out that little tube that you need here and now without having to rummage through ALL boxes (because you forgot where you stored the tube!).

Good data management is time-consuming, but it will pay off!

I already hinted at it, but let me state it clearly: the build-up of boxes means that I have been working, and I must admit – I have been working a lot. Again, I need to go back to something I stated in one of my previous posts, and that is: I love what I am doing, and I see it as a combination of my hobby and my job. I know I am lucky to feel this way, and it is sometimes hard to convince people that it is the way I see my work, especially when they try to tell me that I am working too hard. It is important to know my own limits, of course, and no doubt that everyone needs sleep, but my “working too hard” could also be translated into “playing too hard”, right? And playing is fun.

In this case, playing is also EXPENSIVE. Within less than a month, I have spent more money than I have done in my whole life. Science is really expensive!! This week alone, I have had to order reagents for almost £1,000. Thank you, Wellcome Trust, for funding me!!!! Growing up in a family with multiple accountants, I am more than aware of the value of money, so my heart skips a little beat every time I see my grant money decrease by a significant chunk. This does, however, motivate me to think more carefully about my experiments and to plan well ahead to prevent money and reagent waste.

The experimenter

So what’s the money for? In terms of lab research, I have spent the past month culturing cells and trying to cut and edit their genes using one of the “hottest” molecular techniques on the market: CRISPR! You may have heard of it as it has actually been in the spotlight of the mainstream media (for example: http://www.theguardian.com/science/2015/may/10/crispr-genome-editing-dna-upgrade-technology-genetic-disease). So, let’s break it up a bit to aid understanding:

DNA: during a recent public engagement event, I realised how difficult it is to explain what DNA is to non-scientists. People often seem to have a vague grasp of what it is (hereditary component), but struggle with the actual concept. We all have DNA; it is the chemical material that governs what we inherit from our parents. Each individual gene is a chunk of DNA, but DNA is not only genes – it is also regulatory elements that control when and where such genes are expressed. As an example, imaging if your eyes were growing hair; although different cells in our eyes do have the same genes as stem cells in our hair follicles, only the latter promote hair growth because there is a controlled expression of particular genes in different tissues fit for their purpose.

Cells in culture: it is less fancy than it sounds. Culturing cells can be complicated, but the particular cells that I have been growing so far are very generic; they stem from a human embryonic kidney and have been modified to enable them to be cultured indefinitely. This makes them perfectly fit for my current purposes as I am testing some reagents under development for downstream use in a much more complicated and tricky cell type: human stem cells. Cells in culture is like having a pet. You need to take care of them, i.e. feed them and give them new space to grow when they get too crowded.

Gene editing: again, don’t imagine Frankenstein coming to get you. Gene editing happens all the time INSIDE you in the form of gene repair. Our DNA is subject to multiple chemical modifications and damaging breaks on a daily basis, which – if left unattended – would results in the rapid demise of the organism. As a result, cells have evolved efficient machineries to repair damaged DNA and edit it back to its original state. If you think about cancer, it results from the accumulation of damaging DNA mutations which have not been repaired, ultimately transforming the original cells into cancerous entities.

Gene editing in the lab harnesses knowledge from natural cellular systems; CRISPR, for example, is a tool used by bacteria to protect themselves from bacterial viruses. It can be thought of as a pair of molecular scissors that allow you to cut the DNA and stitch it back together in a slightly different way. Used in the lab, CRISPR has the potential to precisely and easily manipulate any DNA region in a cell. Why is this important? Human diseases are commonly caused by malfunctioning genes, and understanding the underlying molecular mechanisms requires access to cells mimicking the original disease. Obtaining patient biopsies is restricted to a few easily accessible tissues, which are not always the most relevant for the disease of interest, and are difficult to get on a larger scale. CRISPR now allows scientists to take a normal human cell and engineer it into a disease cell model that can be grown and studied in the lab. I won’t delve into the ethical aspects of gene editing apart from saying that the birth of CRISPR-edited babies is unlikely to happen in my lifetime!!!! It is, however, a tremendously useful tool for scientists, rightly described as a revolution in molecular biology. It is therefore not surprising that the two scientists behind the discovery of CRISPR back in 2012, American Jennifer Doudna and French-born Emmanuelle Charpentier, were big favourites for the Nobel prize in Chemistry this year. They did not receive it this time around, but I am sure they will at some point in the future. In fact, I did attend a talk by Emmanuelle Charpentier earlier this month and found her very inspiring!

So back to my own work. I am developing CRISPR-based methods to edit a particular gene of interest in order to model a disease found in our patients (will come back to this in a future post once I have some solid data). Currently, I am in the testing phase, so I am doing simple experiments, trying to get these molecular scissors inside the cells and, most importantly, trying to get them to cut in the right place with subsequent replacement of the DNA chunk of interest. How do you get things into cells? In this particular experiment, I am applying an electric shock to the cells, which temporarily creates pores in their cell membranes (the barrier of all cells), allowing the scissors to enter. I can monitor the efficiency of this process by also putting a DNA piece into my cells, which allows them to become green as seen in one of my microscopy images below (cool, isn’t it?). I don’t have much to report at this point, as a lot of optimisation goes into this process, but please cross your fingers that it will work!

My green cells
My green cells (unfortunately very blurred as I was limited in what I could paste into the post)
The science communicator

Aside from hardcore work, I am also heavily involved in softer work. I have said it before and this blog attests to it: I am an avid science communicator – or rather, I try to become one! In the past year, I have been involved in directing a number of public engagement activities at my Institute but also as a member of the Cambridgeshire branch of the British Science Association. I am now the vice-chair of the latter, which requires frequent meetings and a lot of time spent developing science activities for children and adults alike. Most recently, we took part in Big Biology Day at Hill’s Road Sixth Form College in Cambridge with a room-size cell activity. It was our first time running this event, and although we need to improve, I think we did a decent job. It is inspiring and rewarding to see new volunteers joining the branch, eager to get involved with fun science activities benefiting the public. In fact, I think our branch has made vast improvements in the past year, with new members contributing to a better organisation of individual activities and novel ideas. Personally, I have recently prepared a new Induction Booklet for new members joining the branch or others with an interest in doing so. Our next task is to prepare for The Cambridge Science Festival 2016 which takes place in March next year. It is also one of my main responsibilities because I directed the development of a home-made electronic cell model for the 2015 Science Festival, and would like to take this model a step further by engaging with professional engineers. To this aim, we have recently established a collaboration with the Electronics Workshop at Cambridge University, who have agreed to build a professionally-looking and multifunctional electronic cell model based on improvements to our original design. Specifically, we are now designing an orthodrome cell (roughly 40 cm in diameter) in which the different organelles are modelled by modular components, which can be taken in and out of the cell. Participants will be asked to identify each organelle and locate it within the cell, upon which LEDs associated with each component will reveal if the correct location has been chosen. In parallel, participants will be offered accessible explanations into the functions of each component, and how they work together to keep the cell alive –  once all components have been placed correctly within the cell, a tune and simultaneous flashing of LEDs will signal the establishment of a minimally functional cell. The modular components will include nucleus with DNA, endoplasmic reticulum, Golgi apparatus and mitochondria. To illustrate external communication with the cell, components resembling cell-surface receptors will be studded on the outside of the cell. We will further demonstrate the molecular aspects of viral infections by asking participants to attach a virus model to the outside of the cells, upon which an inner electronic circuit is triggered, which will control the movement of several flashing components (modelling protein complexes) from the surface towards the nucleus, which ultimately activates a buzzer and a red flashing light to indicate viral infection.

For all this to happen, MONEY is required, and I hope that my recent grant application to the Biochemical Society on behalf of the BSA Cambridgeshire branch will be successful!

Communication workshop

There is more to add to the pensieve with regards science communication, though. I recently attended a very inspiring Cambridge AWISE  communication skills workshop delivered by Dr Jane Goodall, who is a senior researcher at Cambridge University. I learnt a lot from Jane, who was engaging and particularly effective at getting her message across (something she tried to teach us!). Some of the key points from the workshop were:

  • Use your own natural conversational voice but with a sense of confidence.
  • Be authentic – do not be afraid of being yourself.
  • Maintain good posture that allows you to breathe!

The next stop on my communication learning curve is hopefully the acceptance of my application to attend two key workshops organised by CUSPE (Cambridge University Science and Policy Exchange): “An introduction to science in policymaking: who, what, why and how?” and “How to communicate your research to policymakers?”. If I manage to get a place, I will use the knowledge gained from both workshops in my preparations for entering The SET for Britain – a series of poster competitions and exhibitions in The House of Commons for early-stage or early-career researchers eager to present their results and communicate them to a lay audience.

The social organiser

What else happened in the past month? Ah yes, I am on the Institute’s Student Committee – as the Public Engagement Officer, but have recently undertaken a new initiative together with one of my colleagues, who also happens to be a very close friend. We are organising a networking event for students and postdocs across the different labs to promote interaction and knowledge exchange. The event will take the form of a Happy Hour with food, drinks and speed networking. I hope we will be successful in getting people to attend and in stimulating collaborations and friendships among colleagues. After all,  there is a survey showing that “all work and no play” is harmful to one’s health, so just another reason to stay social!

The daughter and the friend

As I said, all work and no play is bad health and no fun. This is also true if you don’t make time for your family and friends. Now, this is hard, but crucial! I was glad that my parents were able to visit me for four days, which offered a lot of quality time as well as their presence at my MRes graduation. My second graduation from Cambridge, but still equally “odd” because you’re taken several hundred years back in time – the ceremony itself is in Latin, and you are wearing gowns and distinctly coloured hoods (have a look: https://www.youtube.com/watch?v=4E-AZoMvybE).

Ready for Graduation
Ready for Graduation
Another cheerful event was catching up with one of my best high school friends – with whom I collaborated on every single project in high school – at a formal dinner in Cambridge. Now, what happened is truly incredible. After 2 years since our last meeting, she is now bound to come to Cambridge for 7 months and will in fact end up working one floor below me, in the MRC Epidemiology Unit – of all places! Not only that, her boyfriend has started an MPhil in Pure Mathematics and has happened to choose membership at Clare Hall, same college as me… If that’s not “meant to be”, what is? 🙂

Brain space clearance completed

I think my pensieve is about to flow over. So I will stop here and come back again when able to snatch another free hour for the purpose! In the meantime, more exciting stuff to do – but I must admit that I quite often have to remind myself that sleep is crucial, too.

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