Giles Yeo is a Principal Research Associate in the Metabolic Research Laboratories at the University of Cambridge, Director of Genomics/Transcriptomics for the MRC Metabolic Diseases Unit, and a convenor of the Society’s Neuroendocrinology Endocrine Network. His research focuses on understanding the molecular mechanisms that underlie central control of food intake and body weight.
What inspired you into endocrinology?
I got into neuroendocrinology entirely by accident. I am interested in obesity and I started out studying the genetics of obesity, which involved trying to understand how the brain responds to circulating cues, such as hormones, to regulate food intake. So, I think I am an accidental neuroendocrinologist. I trained as a geneticist under the supervision of Nobel prize winner Sydney Brenner, where I investigated the molecular evolution of complement in fugu, but I soon realised that this wasn’t the research that was going to attract big money, so I decided to transfer my expertise in molecular genetics to an emerging and exciting area – the role of leptin in energy homeostasis. Leptin had just been discovered and Stephen O’Rahilly needed a geneticist to help pin down its role controlling food intake in the brain.
Tell us a little more about your current research
I am currently interested in defining the neuronal networks of hypothalamic pathways using mouse models. We, and others in the field, are particularly interested in the melanocortin pathway. The main genetic players in this pathway were mapped in the late 90s but recent discoveries have reignited interest in this area. For example, together with colleagues Stephen O’Rahilly and Eleanor Raffan, we have identified a major genetic driver that explains why some Labradors are highly food driven, which has also revealed more complexity to the melanocortin-POMC pathway. I am also interested in using single cell RNA sequencing to characterize melanocortin neurons. It is really interesting that we are looking at a pathway that we thought we understood 20-25 years ago and making new discoveries.
What do you think are the biggest challenges in your field?
One major issue with neuroendocrinology, broadly, is the difficulty in accessing human brain tissue, for very obvious ethical reasons. So we use animal models to try and understand the neuroanatomy and physiology. As a result, many in the field have become very accomplished mouse neuroanatomists but I didn’t get into this business to cure mouse obesity! It is a huge challenge to identify the human relevance from these very finely manipulated and studied models.
How do you think these challenges can be addressed in the future?
I am currently working with the Cambridge Brain Bank to get access to post-mortem human tissue to try to understand if some of the specialised neuronal populations and networks identified in mouse hypothalamus actually exist and function similarly in humans. Ultimately, we want to improve human health, so the key is to make sure that the research we do is truly relevant to the human condition.
New technologies, like inducible pluripotent stem cells (iPSCs) can be good models, as you are able to introduce specific genetic alterations. However these are only cell-based models, so don’t grow and develop as they would do in an intact brain. The function of a neuron is very dependent on its environment, where it projects to and what connects to it. Other scientists are working on growing a ‘mini-brain’ in a dish, which is still at the very early stages of development but could lead to better, more integrated models for research. To truly model the system we need a network model but that is extremely difficult.
Are there any controversies in neuroendocrinology? How do you think they will be resolved?
More generally in endocrinology, I think there is a real argument for when is a hormone really a hormone? There are principles for the classification of hormones but new things that don’t really fit the criteria are often designated as hormones. For example, GDF15 was found to be a marker for all-cause mortality, which led to lots of experiments being conducted on different cell types that suggested that it could affect multiple pathways, in a hormone-like manner. However, further research showed that GDF15 actually signals only to a small subset of neurons in the hindbrain, although it may be secreted all over the body, this group of neurons was its effective target. Until you know what the receptor is, it is difficult to understand what a specific ‘hormone’ might be doing; you need to know more about the physiological function e.g. receptor specificity, effective concentration range, speed of effects, what terminates its action, etc. Before you call something a hormone you need a better idea of what it does.
Why did you become an Endocrine Network convenor, and how do you think it could benefit others?
I am passionate about promoting neuroendocrinology and I am the current president of the British Society for Neuroendocrinology, so I decided to also become a convenor of the Society’s Neuroendocrine Network, to help further highlight neuroendocrinology. There are probably a lot more neuroendocrinologists than they themselves realise. Any hormone that signals to the brain is, by definition, part of the neuroendocrine system; it may be the entire pathway or just part of it. We need to get the message out there – that if the hormone is active in the brain, you are involved in neuroendocrinology. I think the Endocrine Networks are a great of way of bringing scientists and clinicians with similar interests together, to promote debate and collaboration. I have also been working with Kevin Murphy & Barbara McGowan, convenors of the Metabolic and Obesity Network, to organise a joint meeting that brings obesity and neuroendocrinology together.
Can you tell us about how and why you got into TV?
Again, I got into this entirely by chance. A Channel 4 programme was looking for an expert to help with a short genetics of obesity segment, which went really well and led to me being invited to contribute to the BBC’s ‘What’s the right diet for you?’ series. As a result, I was asked to take part in a Q&A at Cheltenham Science Festival, which turned out to be really popular among the festival goers. Also, unknown to me, I had just had an unofficial audition. The BBC’s Horizon editor was in the audience and after seeing me on stage offered me my first Horizon show, ‘Why are you getting so fat?’ This was just a couple of years ago and since then I’ve done a show examining ‘Clean Eating’, and now I am a resident expert on the BBC’s ‘Trust me I’m a doctor’. Look out for another Horizon show on vitamins that I have coming up later in the year.
Of course, it doesn’t suit everyone’s temperament to stand up and talk in public or in front of a camera, but I really enjoy doing it. I think communicating science to non-experts is every scientists’ duty but they should choose the level and extent to which they want do it.
Why do you think it is important for scientists to get involved in outreach?
I think they have a responsibility to get involved for two reasons.
- As scientists we put a lot of time and effort into our research to get publications but we should remember that only a tiny fraction of the population will ever read anything published in a scientific journal. The rest of the population pay our salary, so we have a duty to feed back the information funded through taxation.
- In today’s post-truth environment, where people are allowed to be ‘passionately ignorant’ through social media, any content can just be put out there with no editorial, no checks on quality or accuracy and this leads to public argument and disagreement.
A great example of this is the anti-vaxxer movement, which was based on a publication that has now been completely discredited and withdrawn, yet the movement persists. Climate change sceptics often point out that experts themselves disagree about whether or not humans are truly having a major role in climate change, even though the majority of scientific experts do agree that humans have a role in it.
However, when a non-expert views this situation they see two scientists arguing, which leads to what I think is the real toxicity; a perceived ‘expert’ saying something that is ‘BS’ but being given equal or more weight than the actual expert evidence or opinion.
It is also important to highlight to the general public that the scientific process involves debate and evidence. We are paid to argue with each other until we come to a consensus, and then we move on – that is how science works. So, if you happen to be a real expert in an area where there are people being ‘passionately ignorant’, you should speak up, or someone far less qualified than you will!
That’s why I think it is important for scientists to stand up for their science, and communicate their expertise. You don’t have to become a TV personality to do it, there are lots of ways, from becoming a media spokesperson for your university or academic Society, such as SfE’s Media Ambassadors, to attending science fairs, writing articles/blogs, speaking at schools, etc. There are loads of ways of doing public engagement for non-experts.
Finally, what advice would you give to aspiring scientists?
You really have to love what you’re doing and be mindful of telling the truth all the time. I don’t want to sound like a fortune cookie, but if you become lax with the truth in this post-truth era, you are becoming part of the problem.
I also tell my students, “Be more of a pain in the ass to replace than to get rid of” because if you are really useful and don’t cause trouble, they will want to keep you around and you will have better career stability.
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