At the age of 10, I was convinced that I was going to be a forensic pathologist
My love for science arose from an unusual and slightly morbid route. From a very young age, I was obsessed with crime shows such as CSI and Diagnosis Murder. The science of forensics fascinated me, but so did the problem solving required to crack an investigation. As a result, at the age of 10, I was convinced that I was going to be a forensic pathologist (I didn’t have many friends). However, once I started high school, I quickly realised that forensics wasn’t going to be half as glamorous as portrayed on TV. Instead, I channelled this early interest in science and curiosity into studying human biology.
At school, I really loved the practical aspect of science where my skills shone. My biology teacher once told me: “Your coursework and essays are atrocious, but your lab work is excellent”. This was (unfortunately) true, and it resulted in my first failure as a young scientist whilst studying for my A levels (the UK equivalent of Year 12). Based on my predicted grades, I received an offer to undertake a Bachelor of Biomedical Science at the prestigious King’s College London. Much to mine and my parents’ horror, my aforementioned terrible essay writing skills led to me flunking my exams, and I ended up going to a mediocre university located in Bristol. Luckily for me, I loved living in Bristol, and I was thankful for this early failure. It made me realise that I needed to hone my scientific skills outside the lab if I wanted to have a successful career in science.
Again, at university, I felt so natural being in lab practicals. However, I found sitting in lecture theatres and attempting to memorise endless signalling pathways slightly dull. I just wanted to put on a lab coat and start doing experiments. This theme had been so pervasive throughout my studies so I decided to pursue a career in laboratory research following my undergraduate degree. I also decided to do this on the other side of the world. So, at 21, I packed my bags and left the small English town where I had grown up and moved to Melbourne, Australia. At this stage, I was particularly interested in how the brain worked and so I began an internship in the Neural Plasticity and Epigenetics lab at the Florey Institute of Neuroscience. This is where things finally started to make sense for me as a scientist. It wasn’t exactly a lightbulb moment, perhaps more of a slow burning candle, but the barrier that I’d experienced between scientific theory and the work I was conducting in the laboratory had finally started to dissolve.
My interest in epigenetics really took hold at my time at the Florey and I wanted to focus on this for my PhD, so I joined the Cancer Epigenetics lab led by Prof. Mark Dawson in 2016. Until this day, I am not sure why Mark took me on as a student as I had limited laboratory skills, I only had experience in qPCR and mouse brain dissections. He also gave me 2 extremely high-risk projects. The first project was optimising plate based single cell RNA-sequencing to study tumour heterogeneity in patients with leukaemia. The second was to develop a novel single cell “barcoding” technology that would allow the tracking of individual cancer cells over time. At the time, single cell technologies were in their infancy, and I really felt like I was in over my head. Embarking on these ambitious projects is where I experienced my next set of failures, following my exam blunder from all those years earlier.
For the first 2 years of my PhD, nothing I did in the lab worked. I barely had any useful data and I was taking 2 steps forward and 1 step back. I tried to stay positive, but some weeks were bleak. As laboratory scientists, we are so intimately and personally tied to our projects, so it can be incredibly hard not to place blame on yourself when things aren’t working. During this tough period, I had to keep reminding myself that if the technology we were trying to develop was easy, then someone else would have done it already. I somehow found the resilience to persevere and with the help and guidance of many colleagues and friends, things started to finally work. It was amazing how quickly our story came together once the barcoding technology had been optimised. In contrast to how down I was in the early stages of my PhD when things weren’t working, this latter stage of my PhD was some of the most exciting and rewarding phases of my career thus far. Research is a bit of a rollercoaster ride, and you have to experience the low points in order to appreciate the amazing highs.
I’ve now started my postdoc with Dr. Melanie Eckersley-Maslin and I am building upon some of the themes from my PhD in the exciting area of cancer cell plasticity and non-genetic cancer evolution. For decades, the field of cancer research has focused on mutations involving the DNA sequence and how these are crucial for cancer development. However, we now realise that non-genetic factors, such as the transcriptional and epigenetic landscape of cancer cells, might be equally as important in driving tumour evolution. I am incredibly lucky to be working in this exciting area and am hopeful that my research can add a small piece the ever-growing puzzle of cancer biology. I won’t lie- some days, I still feel like that naive girl who could only do qPCR and I still fear that my experiments won’t work. I have to remind myself that I have come such a long way since I started my PhD and each failure I have experienced has taught me something very valuable.
Figure Legend: Single-cell Profiling and Lineage Tracing with expressed barcodes (SPLINTR) a) Three independent SPLINTR barcode libraries were generated, each containing a distinct fluorescent reporter and barcode structure. SPLINTR barcodes are constitutively transcribed upon genome integration, enabling tracking of clonally related cells together with their individual transcriptomes. b) Schematic detailing the experimental design used in SPLINTR experiments to retrospectively identify the transcriptional signatures of dominant clones. This technology was developed as part of my PhD project.
Dr Katie Fennell is a postdoctoral researcher in the Eckersley-Maslin Lab. She has expertise in lineage tracing, single cell technologies and non-genetic evolution in cancer. Work from her PhD has been published in top tier scientific journals, including Nature and Nature Communications and she was a finalist for the prestigious Premier’s Award for Health and Medical Research in 2022. She is particularly interested in cellular behaviour and clonal biology and is currently investigating novel regulators of plasticity in cancer. She can be contacted at [email protected]