The MRC Cancer Unit has a longstanding tradition of engaging with young minds to encourage them into science and cancer research in particular. Towards this, every year we host visits from students to our research laboratories, be it in the form of summer placements (internships) or shorter, week-long visits from school students, with each stint encompassing both theoretical and practical aspects of the latest in cancer research. We believe this experience presents a unique opportunity to those who attend, to gain insight into the world of research, and explore future possibilities in science, in addition to providing us, as scientists, a chance to reach out and enthuse the next generation about how exciting and rewarding a career in science and research can be. This year was no different. We had three young visitors to the Fitzgerald laboratory over the summer and a bunch of curious sixth formers from the Hills Road Sixth Form College in Cambridge who spent a week at the Venkitaraman laboratory. Here is what they told us about what it all meant to them!
Our MRC Cancer Unit Experience!
Overall, the week spent at MRC Cancer Unit was amazing. We were exposed to very current and upcoming scientific topics and were also given the opportunity to use extremely advanced equipment and practice some techniques.
On the first day we learnt how to transform E. Coli bacteria using a technique called electroporation, which we were able to apply to practical work. Tuesday began with a talk by a former Hills Road Student, who has taken time from his medical studies to do a PhD at the MRC Cancer Unit. His talk gave us an insight on how different proteins work together to carry out actions in the cell. In the case of the particular protein that was the topic of the talk, we learnt that it must be degraded in order for the cell to survive, however, if it is allowed to accumulate inside the cells, the cell would be unable to grow and will die. Encouraging this signal may prove important in cancer therapy. Learning this theory helped me to understand how the MRC Cancer Unit lab are trying to better understand how cancer works and what type of research is possible to do in the future. In the afternoon, we completed our work from the day before and learnt that in research not all practicals go to plan, but learning from them is key to discovering new findings!
Wednesday morning, we learnt about proteins; how to run polyacrylamide gels and how to interpret the results. We then moved onto Western blotting. The theory of the three-day process was explained, which involves applying the gel to a sticky membrane. This allows a print to be made of the gel, which can then be ‘probed’ using specific antibodies to show only the protein of interest. We then went into a darkroom and got to use the film processor to collect prints from our gel and analyse them; this was the highlight of my experience even if it was often too dark to see what you were doing!
In the afternoon we were able to see the workings of a very new technique; CRISPR/Cas9. We were explained how this new technology allowed the researchers to make precise, targeted changes to the genome of living cells. Microbes have been using CRISPR/Cas9 for millions of years. It was fascinating to see how we have mastered one of nature’s techniques to turn it into our own advantage and for me, it was fascinating to see the potential that this technology could have, not only in the treatment of cancer but also other illnesses!
Thursday’s focus was microscopy. We watched the loading robot arm in action. It was used to move the plates with cells from the incubator to the microscope stage. Then we used the confocal microscope. Each member of the group located a separate field of view of the cancerous cells, which was then imaged every 2 minutes to show how the added solutions affected the cells. Next, we mounted a cell suspension onto slides, adding cover slips. The cells had been prepared with a dye so that, when we viewed them under the microscope, we could see the nuclei within each cell. It was fun to use such high tech equipment, despite some of the rooms having to be kept at a chilly 16oC so that the microscopes are able to function properly!
Friday was mostly an evaluation of the week. We had a careers session with another former Hills Road student, who is now working towards a PhD. He told us all about life as a student, as well as working within biomedicine which I found very interesting as well as useful for the future. In our feedback session with the scientists from Prof Venkitaraman’s group and Dr Harvey, the head of Biology from Hills Road, we discussed what we liked most about the week – for me it was getting involved in all the practical work, which we do not usually have the opportunity to do at school.
(On behalf of: Alba Saenz de Villaverde Cortabarria, Diana Coroi, Elizabeth Ogilvie, Hannah Kilford, Lucy Wilkinson and Sabina Ray )
Cancer vs Computer Science – new ways of looking at an old disease!
Ben Hall spoke on his work using computer science techniques to understand cancer biology at the Microsoft Future Decoded Exposition, held at the ExCel in London, in November this year. In a programme of talks relating to how computing is transforming society in diverse areas including policing and health care, Ben highlighted how his lab uses concepts taken from the analysis of software and hardware to tackle the unique challenges in fathoming the early stages of cancer development. Here’s a bit more from what he had to say:
Cancer is a major problem in biomedicine. Whilst scientists have made great strides in some types of the disease, we have not been able to reduce adult mortality greatly over the past few decades. My laboratory at the Medical Research Council Cancer Unit at the University of Cambridge works at the interface between computer science and cancer biology, using our knowledge of the disease to build “models” of cancer- that is, mathematical representations that allow us to simulate and test our ideas, and to make new predictions. This work, carried out in collaboration with experimental and clinical collaborators, gives us an opportunity to find new ways of understanding and eventually treating this major illness. This is particularly valuable when considering the earliest stages of cancer, where the research could aid early detection and intervention leading to better clinical outcomes. It requires a new set of tools too, like the BioModelAnalyzer, which I will speak about at Future Decoded. The BioModelAnalyzer, developed by the Fisher group at Microsoft Research Cambridge, allows model creation and analysis through a bespoke user interface. Such tools empower experts in cancer biology to take advantage of the latest algorithms and approaches without requiring them to become computer scientists.
The unique problems of cancer
As a disease, cancer has been recognised for thousands of years. The earliest records of sufferers are from 3000 BC in ancient Egypt (1), where documents and mummified bodies show an acknowledgment, if not an understanding, of the disease. In the modern day, we have made substantial leaps forward in our ability to treat specific forms of the disease. There have been major successes in the treatment of chronic myelogenous leukaemia for example. The overall progress in treating adult cancers has been slow however, particularly when compared with the great successes in other areas such as cardiovascular disease (2).
Two features of cancer present major challenges to our understanding and our ability to treat it. Despite one in two adults developing the disease in their lifetime, from a cell perspective cancer is an extremely rare failure. With 35 trillion cells in the human body at one time, only a handful will develop into cancer over a lifespan. The disease itself results from rare cancer progressing events, occurring in exactly the wrong order. Changing that order may prevent the cancer from growing, or reduce the disease’s aggressiveness (3). It’s hard to spot these rare events early, creating a barrier to understanding how cancers start.
The second problem is biological complexity: within each cell is a large, complex network of proteins, genes, and metabolites that interact and exert different types of control on the behaviour of the cell. Whilst we may be able to draw out some of these networks, our view on the dynamics is clouded by the fact that our understanding is incomplete, with whole pathways and precise physical measurements missing.
A model of cancer metabolism in the BioModelAnalyzer.
Novel solutions through CS
My group at the MRC cancer unit tackles these challenges by using techniques taken from computer science. The tools developed for the analysis of software and hardware systems allow us to address these problems by using abstract models to fight the issue of complexity. Alongside this we use “model checking” approaches that can draw out rare events from a network. They do this by providing guarantees of behaviour backed by rigorous mathematical proofs, ensuring that uncommon cancer progressing acts are found.
This creates a new type of problem; how to get these methods into the hands of the people who can take best advantage of them. One solution is bespoke user interfaces. The BioModelAnalyzer takes this idea forward; a web interface allows bioscientists to construct and analyse models, whilst abstracting the underlying CS research away. In addition to connecting the tools to a new audience, it also speeds up the work of experts in the field by simplifying the model construction process. My own laboratory has used this to understand the role of membrane proteins in determining the cells response to nearby tumours, as well as cellular metabolism and the cell cycle (see figure 1). These new models give us unique insights into the drivers of cancer, and help us explain why some drugs may fail. We can also identify new targets for drug development, and suggest treatment combinations that have not yet been explored. With these unique opportunities, these results show why bringing CS techniques to biology has a bright future!