Dr Alice Pyne is an MRC/UKRI Innovation Fellow and Lecturer in Soft Matter/Polymers at the University of Sheffield.
Her AFM days began over ten years ago working with NuNano co-founder Prof Mervyn Miles and this month she’s about to take on a challenge that we have a bit of a personal interest in – supervising former NuNano sales coordinator Eddie Rollins who has just departed NuNano HQ in order to take up a PhD in Alice’s lab.
We caught up with Alice to talk about AFM community past, present and future and to discover why she believes openness and diversity are central pillars for the future of AFM…
Dr Alice Pyne
If you’ve ever had the good fortune to chat to Dr Alice Pyne, or to hear her talk, you won’t need to me to tell you that it’s an absorbing, engaging and synapse-firing experience.
Her enthusiasm for and commitment to not only her own area of specialism but to the growth and development of a wider, more open, more collaborative AFM community is inspiring. It is a community that Alice has been part of since her undergraduate days.
It was a last-minute switch from Classics to Physics that set Alice on the phenomenal trajectory that has been her science career to date. It wasn’t a straightforward one:
“I was one of 2 girls in my A-level physics class, and when I decided I wanted to change my UCAS application to study physics I had to email all of the universities myself to ask if they’d accept me onto a physics course. A lot of people were really funny about it because it was such a jump. Bristol wanted a new section 10 from me detailing why I wanted to study physics. That’s why I ended up going there because they asked my opinion.”
As an undergraduate Alice wasn’t initially planning to study nanotechnology and was fascinated by particle physics in particular. However, her sister was diagnosed with a chromosome deletion condition at the same time as she was choosing 4th year labs, and the Mervyn Miles’ SPM group had just shown that they were able to image whole chromosomes using AFM.
“Wanting to use these nanotechnological tools to look at things that we can’t normally see in the diseases we don’t know loads about was a clear motivation for me in my final year project.”
So for her final year project, Alice worked with fellow student Will Marks on a project that used AFM to look at the effect of citric acid in sugary drinks on tooth enamel. NuNano co-founder, Professor Mervyn Miles, was her supervisor on it. Alice remembers:
“Will and I ended up doing shift work together on the AFM because the experiments took so long and were so hard to set up. The building work for NSQI was still happening and our lab was right next to the foundations of it. So, we did a lot of set up in the day and a lot of imaging at night. Without Will, I probably still wouldn’t be able mount an AFM cantilever today!”
It was also an induction for her into the AFM community in Bristol:
“It was one of those ‘it takes a family’ projects. We ended up using Arturas Ulcinas’s code on the high-speed AFM that Loren Picco and Oliver Payton had built, working with many other people, including Pete Dunton and members of Terry McMasters group who took some measurements for us on his (much newer) AFM! All of these people worked with us and we managed to get a really interesting project going. All these years later, it’s the kindness of people like Pete, who spent so much time helping us out, that really sticks in my memory from that project”
Alice credits how she operates today within her own lab to her experience during her undergraduate work using the AFM.
“I really believe in the importance of working in a big team with lots of different people from different backgrounds – software engineers, chemists, physicists, biologists – I believe in bringing all of those together as a family to solve really interesting problems.”
Today Alice runs her own lab at the University of Sheffield looking at the structure of DNA, in particular at the double helical structure. Alice explains:
“We look at the secondary and tertiary structure of DNA. We tend to think of DNA as a very boring straight rod that sits in the big bang theory background; most labs have a ball and stick model of a straight linear piece of DNA. But actually, DNA is bent and curved; it’s a polymer with different flexibilities encoded by both chemistry within its sequence but also by physics in terms of actual mechanics and looking at polymer science.”
As Alice explains, DNA is a lot more complicated than we think it is both chemically and physically. Using AFM to examine what is going on has created a complete shift in how we look at DNA today.
“The standard approach to DNA is through bulk studies. We look at crystallography and then we get an average structure. But of course there isn’t a real ‘average structure’ that can be applied when you look at people – we don’t all have brown hair, we don’t all wear glasses, we’re not all 5ft 3.”
Alice’s lab group are interested in what could be described as something of a chicken and egg problem.
“Does the DNA bind something because its bent, or does the thing bind it and bend it? None of these things can be worked out if you look at an average structure, if it’s just there, static, bent. We’re asking is DNA not actually passive? We look at it as being a passive polymer but actually is it active at bending the right place and making loops?
We think DNA is alive and active and when it’s constrained and in a looped form - which it is everywhere, either constrained by proteins or in a circular genome - you can over and under twist it and that makes it do cool exotic exciting things. It turns out it’s doing these cool things all the time and it’s never in its boring straight relaxed normal state, which is how tend to think of it in every interaction that it undergoes.”
AFM is enabling Alice and her team to look at supercoiled DNA structures quantitively, to work out which ones are exciting, and which are not. The power of this research is the interdisciplinary collaboration, combining simulations, AFM and biochemistry to uncover the complexities of supercoiled DNA.
(you can view the pre-print article here)
AFM images showing structural and dynamic diversity in supercoiled DNA minicircles. For more information see pre-print article: Base-pair resolution analysis of the effect of supercoiling on DNA Flexibility and major groove recognition by triplex-forming oligonucleotides
It’s no coincidence, given that NuNano emerged from the SPM group at the University of Bristol, that one of our team is leaving to undertake a PhD with Alice. Having learnt about the wide variety of exciting applications using AFM whilst talking to AFM experts, our Sales Coordinator, Eddie Rollins, will soon find himself on the other side of the fence, to become a future expert himself. Alice says:
“Apparently Eddie heard me talk and emailed me to find out what the PhD was about. We had some cool phone calls where he’d said, ‘Well, can you do this?’ and I said, ‘Well that sounds a little crazy, maybe?’
I’m really excited to have a chemist in the lab! Sometimes us biophysicists can forget that chemists are the glue that holds the biophysics interface together. We can end up focusing on the physics and on the biological implications, forgetting that it only happens because of chemistry.”
In addition to her managing her own team and the new Royce nanocharacterisation lab at Sheffield, Alice is one of the scientific organisers of this years’ RMS AFM & SPM Meeting 2020 (which again, coincidentally, NuNano MD James Vicary is on the RMS committee! It all intertwines in AFM!), due to take place in Sheffield in the summer the conference is now happening online 3-4 November 2020.
In organising the conference with fellow Sheffield colleague Prof. Jamie Hobbs, they discovered that women in AFM are not as well represented online as men, but this hasn’t stopped Alice and Jamie from making sure they’re better represented at RMS AFM & SPM:
“You have to get really deep into Google before you find the women of AFM! Then you look their research up and realise that they’re doing really interesting work and wonder why they were so hard to find.”
In addition to the main conference, Alice, together with Laia Pasquina Lemonche and Loanna Mela have organised a spin-out ‘coffee morning’ on data analysis in AFM with Jamie and Prof. Sonia Contera as they believe the future of the new AFM community is about openness and collaboration. Alice says:
“Open tools, open source, open science. That’s the change we want to see in the AFM community. The hope of UK SPM is to bring together next generation of AFMers to say, ‘how can we work together, can we help each other, how can we get more of what we’re doing into the news?’.”
Openness and community are at the heart of Alice’s personal approach:
“I’ve just finished a project where we developed a program to trace biomolecular structures in AFM which is now on github looking at how we can quantitatively analyse AFM data, how we can make all of those tools open and available. The manuscript is published as a pre-print on BioArxiv, and we are actively encouraging people to contribute to the code.”
(You can view the pre-print article here)
It’s not just about being open with the science for Alice though. As is true for most areas within the scientific community Alice believes there’s enormous room for improvement in terms of diversity and reach within the AFM community. Alice is passionate about moving away from the ‘survival’ experience of postgraduate research for example, which can be imposing and off-putting especially for more marginalised and underrepresented groups of people within academia. In particular Alice cautions against the much-used term ‘resilience’ as a key criteria when looking for PhD students.
“I want to support my students in taking on the challenge of a PhD, and help them through it, not expect them to go it alone.”
Alice feels that her field, DNA topology, provides a great model for a supportive and equitable version of a scientific community.
“The DNA topology field is a very supportive and close-knit community; I have felt really lucky to be a part of it. It is a very balanced community, with many women spearheading research and community within it. I have been very lucky to be championed by the wonderful Sarah Harris. There’s a DNA topology website that we’ve made quite recently, for us all to pass on skills, knowledge and information. At our conferences everyone is treated as a participating equal, there’s no top table.”
With this mindset front and centre of Alice’s research, there’s no better place for Eddie to head to. We’re really excited to see how their research progresses and how they help to shape the AFM community over the coming years.
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