How would you explain your research
We want to improve the drug-discovery process. And we’re doing that by understanding how drugs interact with target receptors. My research focuses on G protein-coupled receptors, which are located in the cell membranes in our body. These receptors translate the hormonal signals in our body, such as an adrenaline rush, into biochemical responses inside the cells that cause, for example, the heart to beat faster.
These receptors are complex signalling hubs that control many different processes inside the cell. We think we can create better drugs by modifying them in a way that they cause very specific signalling events in our cells. A possible analogy is that existing drugs are similar to a master key, opening all doors in the building. The next-generation drugs will be more specific, opening only the doors we want them to open.
What type of conditions would benefit from this research?
G protein-coupled receptors are a very large family of membrane proteins. Humans have over 400 of them that could potentially be targeted. Drugs that are already in use have an impact on many conditions – heart disease, neurological disease, HIV, cancer, depression and so on. The model systems we use are vasopressin receptors responsible for water balance in our body, cannabinoid receptors for general cell homeostasis balance as well as inflammation, and adrenergic receptors responsible for heart and lung diseases. We’re trying to understand the principles of how these receptors work at the molecular level.
How does your research benefit society?
If we’re successful we will come up with approaches leading to the development of new drugs that are more efficacious and have fewer side effects. We could also significantly speed up their development cycle.
How does your research fit in with the wider work of the School of Life Sciences?
It’s a fantastic fit because the school has enormous breadth of expertise in pharmacology, from medicinal chemistry, to the molecular pharmacology level, to physiology and the level of organisms. We are right in the middle of this. It’s a great environment.
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Can you tell us about the Centre of Membrane Protein and Receptors?
COMPARE is a joint venture with the University of Birmingham. It’s a growing centre involving around 25 research groups looking at different aspects of how membrane receptors function in cells and tissues. We use technology such as super-resolution microscopy to see where in the cell the receptors are and what happens when they signal.
We also use NMR [nuclear magnetic resonance], which Nottingham has a proud history in, to look at protein molecules and interrogate individual atoms inside them to see what happens to them.
What is it about this research that inspires you?
I’ve always liked the idea that my research should have some practical outputs and application in the real world. G protein-coupled receptors are a big family of therapeutically important proteins. As their molecular architecture is similar, what we have learned about one receptor would often be true for another. So the potential impact of our work is very large.
What have been some of the significant achievements in your career?
Having worked in basic research all my life, I’d say being able to develop several novel concepts that are applicable to drug discovery.
What advice would you give to young researchers starting out?
I had to find an area that stimulated me. I would suggest trying out many different research areas at undergraduate level to see what it is that excites you, and then choose a good research lab where you can work towards your PhD.
If you weren’t doing this what would you be doing?
Something related to the Internet of Things. Electrical engineering and programming are areas that interest me, and I find automation projects in the lab or at home a lot of fun.
What are the biggest challenges for researchers in your area?
One of the challenges is translating all our basic knowledge of how receptors work into the output of developing new drugs. We’re now getting to the point where we understand a lot more about how they work, compared to 10 years ago, but now we want to make the next step and really change the practices of how we’re developing new drugs. It’s something that’s starting to happen.
What would you say to researchers thinking of coming to Nottingham?
This is a most exciting, collaborative space. It’s a fantastic community and you’ll have access to a high level of expertise. We’re a really exciting place to be.
If you were thrown 100 years into the future, what’s the first thing you’d look up?
In science fiction movies they put people in a scanner and are able to see what’s wrong with them and even repair the damage on a spot. That’s the kind of thing I’d like to see. I would imagine, it could be based on some combination of MRI, CT-scanner, functional assays and artificial intelligence to provide the diagnosis. I really hope we’ll see that one day. That would be cool.