Meet the Endocrinologist: Caroline Gorvin, expert in hormone receptor cellular physiology

Dr Caroline Gorvin is an Institute of Metabolism and Systems Research Career Development Fellow at the University of Birmingham. Her research focusses on the trafficking and signalling of membrane proteins, particularly GPCRs and how impairments in these proteins and their signalling pathways contribute to endocrine disease. In this interview, Caroline tells us more about her research, involvement with the Society and her roles as convenor of the Society’s Bone and Calcium Endocrine Network.

Can you tell us what inspired you into research?

My year in industry, which I spent at AstraZeneca during my undergraduate degree, really changed my perspective on research. Prior to this, I wasn’t even sure I wanted to do a PhD, but the experience of scientific research really ignited my interest in membrane proteins, which I have, in some way, continued to work. I accidentally became an endocrine researcher because of this initial interest in membrane proteins and receptors. I realised that genetic abnormalities in these proteins often manifest in endocrine disease, and that by studying these mutations we can learn fundamental concepts about cell behaviour that may help in the treatment of patients with endocrine disorders.

Can you tell us a little more about your current research?

In the last five years, my research has focussed on the calcium-sensing receptor (CaSR), which is a G-protein coupled receptor that has an important role in calcium homeostasis. The CaSR is a great receptor to work on because both loss-of-function and gain-of-function mutations cause disorders of calcium homeostasis, with opposite phenotypes. By studying these mutations in vitro we have been able to understand how individual residues play a role in receptor activation and mediate coupling to specific signalling pathways.

I have found my most recent research, focussed on how mutations in a subunit of the adaptor protein-2 cause hypercalcaemia really fascinating. We could never have predicted that a protein, which is known to play a fundamental role in clathrin-mediated endocytosis, would be the cause of hypercalcaemia. By studying these mutations I was able to uncover novel signalling and trafficking mechanisms of the calcium-sensing receptor, which could represent new therapeutic targets. This project also gave me the opportunity to collaborate with lots of people, and learn new techniques, which to me are the most exciting parts of being in scientific research.

Over the last decade or so, what do you think have been the most impactful advances in this research area?

I think the technological advances in the last decade have really had the most impact on all scientific research. We can now rapidly introduce specific mutations into genes, sequence the whole genome in individual patients and visualise single molecules in cells. These advances have the potential to reveal minute details about cellular and whole organism physiology, expand our knowledge of disease mechanisms and fundamentally improve patient treatment options.

What do you think will be the next big or important breakthrough in bone and calcium research?

I think long-term regenerative medicine is probably the biggest goal in bone and calcium research. With an ageing population, skeletal disorders such as osteoporosis are increasing in prevalence. While we have good therapies to manage symptoms, new technologies offer the possibility of treatments with fewer side effects. Many advances have been made in this field in recent years, and with improvements in bioengineering and iPS cell technology, long-term bone regeneration is becoming a feasible possibility.

What do you think are the biggest challenges faced by researchers?

I think the biggest challenge all researchers face is funding. In endocrinology, where much of the research is into rare disorders, and therefore necessarily niche, it can be difficult to persuade big funding bodies of its importance. There seems to be a wider field of competition, for an ever-decreasing pot of money. Combined with the sometimes poor career advancement opportunities, particularly for basic science researchers, I think these difficulties pose the biggest challenges rather than research specific difficulties.

Are there any controversies in your research area? How do you think they will be resolved?

There are always controversies in any research area. Instead of creating hostility, these controversies should be used as an opportunity to debate and explore new ideas. One of the fantastic things about science is that we don’t know the answers. We should enjoy exploring differing opinions through debate and further research.

You were awarded a Society Public Engagement grant in 2017, why do you think it is important for scientists to get involved?

While many people realise that scientific research takes place, what this actually entails is largely unknown. By introducing people to our work in a fun and informative way, I think we can help make this clearer and gain more support for what we do. Public engagement is really important for science and is mutually beneficial. By encouraging participation we can attract the next generation of scientists, and by sharing our ideas with the public, we may gain new perspectives to enhance our future research.

What attracted you to becoming an Endocrine Network convenor, and how do you think the Networks may benefit others?

To be honest, I was nominated for the position, and hadn’t previously considered that such a position was open to someone relatively early in their career like myself. Initially, when I first started attending the SfE BES conference as a PhD student, it really felt like bone and calcium science was a neglected part of the meeting. This has been changing in the last five years or so, with more bone and calcium research on the oral programme – but I still think research, and collaborations within the field, could be promoted more and the network is good platform for this. One way in which myself and Jeremy Turner, my co-convenor for the network, have been trying to do this is by increasing communication within the network, and giving members the opportunity to say what they want from the network. The network has great potential to generate discussion and new collaborations between basic and clinical scientists – I guess we’ll see how successful this has been at this year’s SfE BES conference!

Do you have any words of wisdom for aspiring endocrinology researchers?

I think the best advice for anyone in research is not to be too disheartened by failure. Just remember everyone in research will have had days where experiments failed, or had papers and grants rejected. We often don’t realise this as PhD students, but it is a valuable lesson that everyone should learn in their scientific career.

The Endocrine Networks are platforms for knowledge exchange and collaboration amongst basic and clinical researchers, clinical endocrinologists and endocrine nurses. The Networks enable members to discuss and find solutions to challenges within their specialist field.

To join an Endocrine Network login to the ‘My profile’ section of the Members’ Area and select ’Endocrine Networks’.

Gareth Leng is the Professor of Experimental Physiology in the Centre for Discovery Brain Sciences at the University of Edinburgh. His multidisciplinary research uses electrophysiology, molecular neuroanatomy, behaviour and computational modelling to investigate hypothalamic neuronal networks. He is particularly interested in pituitary hormones and in the regulation of appetite and obesity.

Prof Leng has just published a book: The Heart of the Brain; The Hormones of the Hypothalamus. In his guest blog, he explains how neuroendocrinologists see the brain differently and why he wrote the book…through a conversation with himself.

Gareth: So, congratulations etc., I’m sure it’s a wonderful book, but before we get to what it’s all about, why did you write it? – apart from fame and fortune, that is.

Gareth: Well (modestly) thanks etc. I’d always wanted to write a book – well, since I was 7. Finally I got the chance to see if I could.

Your students wouldn’t let you into the lab any more so you had some free time?

No. The University abhors a vacuum, and fills all available time with superficially reasonable but pointless demands. The chance came in finding something that I thought was worth saying…

…that you hadn’t said in your last 200 papers?

I hadn’t put it all together.

So, 200 papers without the draggy bits? Quite a short book then. What’s your message?

I wanted to write about what doing science was really like – to talk about the passion and the messiness and the confusions and the mistakes and the mixed messages…

…but not the draggy bits. What’s your message?

I wanted to contrast how neuroendocrinologists understand the brain with the conventional view of the brain as this super, smooth, efficient, dessicated, calculating machine with ten billion neurons and a trillion connections all pinging away.

What do neuroendocrinologists see in the brain that’s different?

Passion and messiness and confusions and mistakes and mixed messages.

That is interesting how exactly?

I don’t think it’s interesting that complicated calculating machines can be good at calculating. To me the challenge in neuroscience is to see how noisy, messy, error-prone systems, self-assembled with quite a lot of randomness, can do clever things, including things that complicated calculating machines are rubbish at.

How is that then? You are pretty noisy and messy yourself but…

A lot comes down to mixed messages. Neurons don’t use just one type of signal – they use many. Some, neurotransmitters, do signal precisely from one neuron to another. Others are local signals, affecting neighbouring cells either of the same type, or of other types, or both; they are signals that pass from one population of cells to another – these are autocrine or paracrine signals. Yet others are released from one population of neurons, spread to large parts of the brain through the extracellular space, and act at distant targets.

Hormones, then, brain hormones?

Exactly. We’ve thought of neuropeptides as another class of neurotransmitters. That’s nonsense. Like hormones they have a massive range of effects, not just on neurons, but on neurons they can have both organisational and activational effects, on gene expression and connectivity as well as on excitability. They can ‘re-program’ their targets in a context-dependent way.

For example – oxytocin as a wild left-field guess?

Yes, oxytocin is a good example. It’s not just released from the pituitary, it’s also released in the brain – but not mainly from nerve endings but from dendrites. That release is governed, not just by electrical activity, but also by peptides that trigger mobilisation of intracellular stores.

Like endocrine cells then?

Oxytocin cells are hybrids of neurons and endocrine cells. They are multifunctional in that the release from dendrites and axons can be regulated independently. They speak in different languages to different listeners.

And so they can do wonderful things…

Oh yes, like generate the synchronised bursts that trigger pulsatile oxytocin release in suckling

…and promote sexual behaviour – lordosis and penile erection?

Certainly.

…and maternal behaviour and bonding in monogamous species?

Apparently.

…and trust and hugs and cuddles…

Enough.

Just about oxytocin?

No, stress, reproduction, appetite and obesity, plasticity, rhythms, evolution…

How did you go about writing it?

Writing the book was for me a way of testing out whether the message held up – in that sense it is a conversation with myself.

Not like this then?

You’re quite right. No. An argument with myself.

Who did you write it for?

Myself really. I read a lot of science books…

…you start a lot of science books…

…and the ones that engage me handle the science seriously but get an interesting message across – they don’t just say stuff. I tried to write the sort of book that I might read to the end.

Have you read it to the end? What’s the last line?

“The hormones of the hypothalamus- the heart of the brain- […] are the signals of emotional salience, the links between our passions and our reason, the agents of our urges, our hopes, our fears – of the things that make us human.”

There are many different types of public engagement, including writing blogs or books on science for general audiences. The Society can help you find the right outlet for your science outreach talents. Visit our public engagement webpages for inspiration, opportunities and more information.

On the 5^th of September 2016, news broke of a study which showed that taking Vitamin D supplements in addition to asthma medication cuts the risk of severe asthma attacks and the number of people needing steroid treatment. BBC World News contacted the Society for Endocrinology for expert comment on the story – here Honorary Associate Professor at the University of Warwick Rosemary Bland describes what she learned from the experience and leaves her top tips for dealing with the media.

My Tuesday started off pretty normally. It was around 10.30 in the morning and I had just returned from B&Q with a car full of compost and wood when my mobile rang. It was the press office at the Society for Endocrinology, wanting to know if I could do an interview for the BBC.

“Phone or radio?” I asked.

“Live TV,” they responded.

My instant reaction was to try and get out of it, thinking about my appearance as I was decorating the house. I gave some names for other experts in the field but I‘d barely had time to consider my lucky escape when a BBC producer rang. I guess they couldn’t contact my scapegoat!

It was exactly 10.41AM and I was asked if I could make it down to the London studio for 12.15PM. This is where the speedy nature of journalism and my first lesson really sunk in – what would be a stressful, logistical nightmare for most is just a regular request from the BBC.

London was out of the question. Luckily, Coventry has a BBC studio and a taxi was booked to pick me up at 11.45. The producer asked me a few questions to give the interviewer some background on the subject and she asked who I was and what I did so they could introduce me. Easy enough? Actually I found it difficult to decide.

I know a lot about vitamin D, but what did I know about this asthma study? Not much more than I’d seen on breakfast TV that morning. After a quick Google, I found all 71 pages of it. Here was the second lesson: you will not have time to do any homework in detail.

After absorbing what I could, I began to think about how the only thing I had to sort out now was myself (no hair and makeup in regional studios). However, remember the quote from Alien “in space, no one can hear you scream” well when on BBC World News ‘no one in the UK can see you’, so that was strangely comforting.

The third lesson was on how to dress. The microphone clips on, but the wires go inside your clothes. A blouse was easy; a dress would have been more difficult. In regional studios the camera only grabs your head and shoulders, so shoes don’t matter, but the white blouse was too pale (I’m wearing a coloured top next time). The cameraman kept in touch with London, but it’s weird not being able to see the interviewer. Try not to glance at yourself on the adjacent TV – it doesn’t help.

The next thing I knew, Philippa Thomas in London was introducing me to the hundreds of millions of viewers watching BBC World News around the world.

Like a politician might do, I had thought of three main points I wanted to get across, so I found myself answering her questions that way. Is that a good idea? I don’t know, but it gave me something to focus on and I found that helpful. Here is one of the most important lessons – think about what you want to say, don’t rely on the interviewer’s questions. This is especially important for public health messages where caution needs to be urged. Just try and remember that you are the expert. As it was World News, I also had to remember not to be UK specific – so not ‘the NHS’, but ‘health services’.

Whether it was the producer (get a phone number for your BBC contact just in case and text them afterwards to ask for the clip), Coventry staff, or the VERY calm man in London who talked into my ear, everyone at the BBC was efficient and helpful. Remember that they do this every day, and so if they have forgotten the little things that might be worrying you; just ask.

When I rang the press office to tell them I was doing it they asked if I was excited. At the time it didn’t feel like it, but after it was all over I think I was. Would I do it again? Probably, but I hope I get the call when I’m not decorating.