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Improving Crystal Quality

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An Interview with Professor Naomi Chayen, Head of the Crystallization Group in Computational and Systems Medicine, Imperial College London.

Winner of prestigious awards, including Innovator of the Year, and nicknamed the ‘Crystallization Guru’, Professor Naomi Chayen tells us a little about her career and the work her lab is doing to help advance the crystallization field.

Q: What originally led you to become interested in science and structural biology in particular?

A: I took a degree in pharmacy as I wanted a vocational subject. I never actually worked as a pharmacist since I was offered a PhD studentship in Biochemistry. I carried on pursuing research when structural biology, of which I knew nothing about at the time, came my way. With trepidation, I took the plunge thus gaining exciting new horizons to my science and life such as receiving awards from Royalty, working with Russian astronauts, media interviews, commercialisation and more…
There has been no looking back since, and three decades on I am still here with the same enthusiasm and vigour trying to come up with new innovations and ideas all the time. 

Q: What have some of your most rewarding achievements been so far?

A: I would say that for me, the most rewarding achievement is making a difference to the field by developing a variety of novel methods for obtaining successful crystals that have led to structure determinations of numerous proteins including membrane proteins and large macromolecular complexes that had previously failed to crystallize using conventional techniques. Translating my scientific research into practical applications has enhanced the impact of the research.

Another satisfying aspect is leading multidisciplinary research - especially when unconnected fields are combined, resulting in breakthroughs. For example, tying together research on bone tissue regeneration or biosensor research to the crystallization of macromolecules. 

Q: Aside from science, what are some of your interests and passions?

A: I am passionate about skiing. It is a unique activity that enables one to keep improving but at the same time to switch off totally and relax. I also love travelling and exploring new places and cultures.

Q: Can you tell us a little about your lab's research directions?

A: Research in my lab has two main strands which are interrelated: The first is developing a fundamental understanding of the crystallization process and exploiting this to design practical methodology (including high-throughput methods) for producing high-quality crystals of medical and industrial interest. The second, is crystallizing target proteins for structure determination and rational drug design. At the moment we are working on the crystallization of proteins related to cancer, HIV, diabetes and heart disease.

Q: What are some of the challenges faced during crystallization of proteins?

A: Getting no crystals at all, obtaining tiny, low-quality crystals, phase separation or amorphous precipitate, and most frustrating: attaining large, beautiful crystals that do not diffract a single spot!

Q: What are nucleants, and how can they help the crystallization process?

A: Nucleants are materials that induce nucleation and formation of crystals. Nucleants can be made of protein or non-protein materials. They help the crystallization process by serving as an anchor or template for the protein molecules to stick to and gather around. Nucleants can be used at the screening stage to facilitate the initial appearance of crystals and also at the optimisation stage of crystallisation to aid in the improvement of crystal quality. Two nucleants have so far been commercialised, ‘Naomi’s Nucleant (2009) and ‘Chayen Reddy MIP’ (2016) and further products are in the pipeline.

Q: Can you tell us more about the potential of carbon nanomaterials as nucleants?

A: The carbon nanomaterials harness the power of graphene. This so-called 'wonder material' is formed of a single layer of atoms, and has been proposed for a wide range of technologies from touch screens to satellites. For the purpose of designing nucleants, polymers are attached to the graphene; the polymers appear to define small pockets on the graphene surface, a bit like a baking tray. These grafted molecules help attract the proteins, and confine them in small regular clusters. This helps them to nucleate a crystal which can be analysed using X-ray diffraction.

Q: Based on your experiences, do you have any advice for those considering embarking on a career in science?

A: We need scientists for progress in every field. My advice for those considering embarking on a career in science is, don’t be afraid of failure, persevere, use your imagination and make it fun!

And if you can, choose the environment and the people that you work with carefully. From a personal point of view, having a superb environment to work in at Imperial College and a great team enables me to be productive and to enjoy the work.

You can find out more about Professor Chayen and the work being carried out in her lab here https://www.imperial.ac.uk/people/n.chayen 

Professor Chayen was speaking to Anna MacDonald, Editor for Technology Networks.