This festive period, Three Wise Women from the Faculty of Medicine will be giving us the gift of wisdom.
Aylin Hanyaloglu, Professor in Molecular Medicine in the Department of Metabolism, Digestion and Reproduction, reflects on the role of serendipity in both scientific discovery and her own 17-year research career at Imperial. She explores how unexpected findings—like those in her team’s research on G protein-coupled receptors (GPCRs)—can lead to breakthroughs that shape the future of medicine. From fertility treatments to the quest for more precise drugs, Aylin discusses how curiosity and embracing the unexpected have driven her team’s progress.
Serendipity—the fact of finding valuable or interesting things by chance—has long been a key element in scientific research. This is exemplified by Sir Alexander Fleming’s accidental discovery of penicillin, which revolutionised medicine: “I did not invent penicillin. Nature did that. I only discovered it by accident.” With this definition, serendipity for me has played a significant role in both the discoveries in our research as well as my career journey. This time of year offers opportunities to reflect on different areas in our lives, and I have often used the term serendipity for describing my journey. But what do I mean by this? Is it needed or just a normal part of the discovery process? And with the rapidly evolving landscape of how science is conducted, will this continue?
My team’s research focuses on a super group of proteins called G protein-coupled receptors (GPCRs), which are found in cell membranes—thin barriers that protect cells and control what goes in and out to keep them functioning properly. The human body has over 800 types of GPCRs, making them essential for cells to communicate with each other and ensuring that every organ in the body works properly. I like to think of them not just as sensors helping individual cells respond to their surroundings, but as part of how we, as individuals, interact with the world around us. Whether it’s the joy of watching a classic Christmas movie while savouring a mince pie and glass of mulled wine, or managing the mix of happiness and stress the festive season can bring, it all involves the activation of different GPCRs. Some of the receptors we study are essential for reproductive health, including pregnancy. We’re also interested in GPCRs in the gut that respond to metabolites, small substances produced when our body breaks down food or drinks. A key challenge in our field is that while many medications target GPCRs, there’s an unmet need for more precise drugs with fewer side effects and longer-lasting effects. Developing these improved drugs requires an in-depth understanding of the molecular machinery that control how these receptors work.
“Serendipity for me has played a significant role in both the discoveries in our research as well as my career journey.”
Unlocking new treatment possibilities for PCOS
One important example of serendipity in my team’s research comes from a single microscopy experiment. Many GPCRs, when activated, move from the surface of the cell to compartments inside the cell called endosomes. Since my PhD, I’ve been interested by how a receptor’s location in the cell can impact its signal activity. This particular experiment took place in the early days of establishing my research team. I was working alongside my first PhD student and postdoc on what we thought would be a straightforward experiment to track how a GPCR for luteinising hormone (LH)—a key hormone for fertility and early pregnancy—moves inside the cell. We expected the LH receptor to behave like other GPCRs, moving inside the cell in a similar way. Instead, what we saw was surprising: the LH receptor ended up in endosomes that looked completely different from what was expected. Was this just an unusual observation, or a clue to something more significant?
Driven by sheer curiosity, I encouraged the team to delve into this a little more. This one experiment set us on the path to developing new models of GPCR signalling—essentially mapping a new ‘island’ in our cell atlas. What’s amazing is that other GPCRs, both inside and outside of the reproductive system, use this ‘island’ for signalling. Even more exciting is that it has given us important insights into health conditions caused by faulty GPCR signalling, and we now know we can tinker with this pathway pharmacologically to help fix it. Together, we believe we can find new therapeutic ways to target and reprogram these receptors. For the LH receptor, which has become our prototype for this pathway, we believe we’ve found promising options to help women with certain forms of polycystic ovarian syndrome (PCOS). This could provide a therapeutic solution not only for women seeking fertility treatment, but also for women who live with the everyday challenges of this condition.
It’s been a 15-year journey from that first observation to where our work is today. Looking back, there were times when I wondered if taking a different approach might have led to results more quickly, given the pressures of academic life. It took five years alone from that first experiment to publishing our findings. This period also coincided with having my two children, and there were at least two years spent convincing others that what we were seeing wasn’t just an anomaly. However, this challenge ultimately helped strengthen the data we had.
“For me, serendipity is a form of nurturing creativity, open mindedness and the innate inquisitiveness that inspired me to pursue a career in scientific research.”
Can AI replicate the human touch in serendipity?
Are these serendipitous events necessary in research? No, I don’t think so. It’s obviously not something we plan for in our grant proposals. But serendipity can come about in a variety of ways, and for me, it is a form of nurturing creativity, open mindedness and the innate inquisitiveness that inspired me to pursue a career in scientific research. As we move towards a rapidly changing, AI-driven world, there’s already been growing debate about how AI will shape the future of scientific discovery, including whether it can replicate serendipity. If serendipity is about ‘lucky mistakes’, then AI can simulate and learn from permutations of experiments at a scale and speed beyond what any individual or team could achieve. But what about creativity or the perceived value of these AI-driven findings? This is perhaps where serendipity, as a distinctly human concept, stems from—the stories of human endeavour that we value. I am certainly embracing a faster pace of discovery science, one that ultimately accelerates advancements in health for us all. Whether serendipity will continue to be part of our scientific stories remains to be seen.