Using Fungi to Study Telomeres

I spent my summer working with the Ferreira Lab in the School of Biology. Dr Ferreira and his team are interested in genome dynamics, particularly chromatin remodelling and telomere maintenance. After a lab tour and a cup of tea, Dr Ferreira helped me map out a project that looked at the role of the SUMO modification during telomere elongation. To do this, he explained, I could use a yeast system that allowed me to induce elongation and then purify SUMO modified proteins for identification. It’s a nifty idea, I promise, but the execution was somewhat messy.

Telomeres are the protective structures found at the ends of our chromosomes. Over time they get shorter until a critical length is reached and their protective function is lost. Some cells, like stem cells and tumour cells, are able to circumvent this by elongating short telomeres. Fundamental questions about how the elongation response is coordinated remain, and my project aimed to identify whether the Small Ubiquitin like Modifier (SUMO) protein is involved. To do this I would genetically modify yeast to express a tagged SUMO protein that I could use to purify SUMOylated targets. If I could identify the targets of SUMO I could infer the functional role of the modification during elongation.

Working with yeast as a model system came with some challenges, although not the interesting sort that biologists working with livelier organisms face. Yeast are tough fungal cells that persist in the presence of damaging enzymes and various mechanical stressors. This means that litres of culture are required to obtain a high yield of protein for analysis. I spent many days transferring yeast from one culture medium to another and waiting for them to grow enough of my precious SUMO proteins.

During this time I gained an appreciation for the patience and persistence that many scientists must have. From the conception of an idea to the publication of a research paper, the scientific process is a long and complex one. My research project allowed me to experience this process in a way that undergraduates rarely get to. The lab was quiet and slow over the damp Scottish Summer because most people were holidaying in places with more sun and significantly less yeast. The contact I had with my supervisor was limited as he was busy writing a paper, but this allowed me to work almost independently. I made many mistakes during the initial weeks but with practice and a little help from the PhD students, I was working confidently and more efficiently. I picked up new lab skills, attended weekly team meetings and learned how to troubleshoot problems.

Unfortunately, I was unable to achieve my goal of discovering something new, albeit small, in the field of telomere biology. When I began to organise the finer details of the project I felt confident that nine weeks would be a comfortable timeframe. Thirteen weeks and litres of yeast culture later, I realised that I was naïve. Reading the blog posts of my fellow Laidlaw Scholars, I noticed a theme – research is unpredictable and at times frustrating. I certainly felt frustrated when I discovered that the protein tag I was using was inappropriate for my experiment and rendered weeks of work unnecessary. However, an important and sadly underreported aspect of science is that negative results often guide us in the direction of the correct conclusion.

Messy lab featuring me and some yeast cultures

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