Press release for our work on tracing complex DNA topologies!

A press release reporting on our recently published work on automated tracing of complex DNA topologies is now available here. We’re delighted to see this work gaining recognition from the wider community!

Within the press release, Alice states “This is the first time we have been able to determine the structure of individual complex DNA structures found in cells with nanometre precision. We have done that by developing advanced new image analysis tools that can do in a matter of seconds that before may have taken hours.”

Paper on automated tracing of complex DNA topologies published in Nature Communications

Our group’s latest research on “Quantifying complexity in DNA structures with high resolution Atomic Force Microscopy“ has been published in Nature Communications. In this work, we present a novel approach for automated tracing of complex DNA molecules from AFM images, showcasing how this enables detailed quantification of individual DNA conformations and accurate classification of their topological states. The paper was an exciting collaboration between experimental and computational members of the Pyne lab, as well as Dr. James Provan and Prof. Sean Colloms (University of Glasgow), Dr. Renáta Rusková and Dr. Dušan Račko (Polymer Institute of the Slovak Academy of Sciences), and Dr. Neville S. Gilhooly and Prof. Agnieszka Gambus (University of Birmingham). You can read the full paper here!

The timing of the paper’s acceptance was especially meaningful, coinciding with first authors Dr. Elizabeth Holmes and Dr. Max Gamill’s PhD vivas… a well-earned highlight they were proud to share with their examiners!

Physics of Life 2025

This week Tom, Tobi, Sylvia, Eva, Kinga and Alice attended the Physics of Life conference at Harrogate Convention Centre. This was the second edition of this biennial event, representing science at the interface between biology and physics. Tobi has provided his perspective on the conference -

“It was an absolute joy to attend POL 2025 in Harrogate this week. This conference brings together biophysicists from around the world for four days of fascinating talks, discussions, and discoveries. From single-molecule techniques to organism development, from computational simulations to cutting-edge microscopy, the breadth of topics covered was truly inspiring.

One of the most exciting aspects of POL is how it showcases the diversity and dynamism of biophysics. The field is constantly evolving, integrating new technologies and ideas to uncover the fundamental principles of life. Each talk and conversation reinforced just how interconnected different disciplines are—whether it’s physics, biology, chemistry, or data science, biophysics sits at the heart of them all.
Beyond the science, what made this conference truly special was the people. Engaging with researchers from all over the world, hearing about their work, and sharing ideas was a fantastic experience. The passion and enthusiasm in every discussion reminded me why I love being part of this community.

As I leave POL 2025, I feel energised, inspired, and more excited than ever about the future of biophysics.”

The group took advantage of the gorgeous Yorkshire weather and visited the Harrogate Gardens

There were many excellent talks on offer, but the standouts included Lorna Dougan’s fantastic talk on studies of protein networks, Erin Cutts discussing her brilliant work on Top2a using optical tweezers, and Aakash Basu explaining the use of his Loop-seq technique to study DNA flexibility.

During the conference, Tom, Tobi, Sylvia and our visiting PhD student Eva presented posters on their current work in the lab. These sparked lots of interesting discussion and questions!

Tobi and Eva presenting their posters

Alice also chaired an interesting discussion with Raveen Tank on the future and direction of the Physics of Life community. Lots of interesting and important points were discussed including how to support researchers within the community (especially ECRs) and how important it is to remain strong in the goal of improving inclusivity and diversity within research.

Alice and Raveen chairing the culture and environment roadmap session

Tom attends AFM Outreach workshop in Manchester

Earlier this month Tom attended the '“Knowledge of the Nanoscale: Developing AFM Activities for Outreach” workshop hosted by the Royce Institute in Manchester. It was a fantastic two days of talks, break-out sessions and discussion about everything outreach! Talks included a fantastic one by Edwin Hwu who described how to ‘hack’ an AFM with everyday consumer electrical including a Nintendo Wii! There was also sessions dedicated to assembling a home-made AFM from scratch (which you can see in the picture below) and then designing outreach activities which could be used in schools to inspired the next generation of AFMers!

Paper on copper metallodrugs published in Nucleic Acids Research

Tom and Alice have published a paper with collaborators from Dublin City University on the “Design and in vitro anticancer assessment of a click chemistry-derived dinuclear copper artificial metallo-nuclease”. The work was an exciting collaboration with Andrew Kellett and his lab, in which we visualised the DNA-condensing effects of their novel anti-cancer metallodrug compounds. If you would like to now more you can access the paper here.

Alice hosts the Insigneo Institute "Imaging Life" workshop

We kicked off the festive season this year with the Insigneo Institute’s first workshop on “Imaging Life”, co-organised by Alice and Jamie Hobbs. It was a real pleasure to host our external speakers Gail McConnell from the University of Strathclyde and Dr. Raveen K.G. Tank from The University of Manchester for our Insigneo Imaging workshop. Thanks to them both for coming and for giving such engaging and inspiring talks 🔬

The day was a real success, with excellent talks from Ankita Ray, Ruby Peters, Andy Swift, our close collaborator and friend Matt Newton and Laura! We had a very engaging flash talk session sponsored by Exciting Instruments featuring Libby and Tom!

The day included a discussion session where we talked about what’s next for “Imaging Life” at Sheffield and what we can do to best support our members, as a result, we’re already planning our next event, which will focus on Data Analysis in early 2025.

Alice attends EU Project SPM4.0 kick-off meeting - PhD position opening soon

In November, Alice travelled to Barcelona for the kick-off meeting of the SPM4.0 project, an innovative Marie Curie Skłodowska Doctoral Network (MSCA-DN) designed to advance the capabilities of Scanning Probe Microscopy (SPM) and revolutionise its application in Life Sciences and Medicine.

SPM4.0 researchers meet for the first time at IBEC, Catalunya

As part of the Marie Skłodowska-Curie Actions Doctoral Networks (MSCA-DN) programme, the SPM4.0 project will be funded for 4 years with around 4 million euros. During this period, 16 young researchers will be trained in the science and technology of autonomous Scanning Probe Microscopes powered by Artificial Intelligence.

One of these positions will be based in our group at the University of Sheffield and will be advertised shortly. The recruited researcher will receive state-of-the-art multidisciplinary scientific training in advanced scanning probe microscopy and machine learning, and its application in biological and medical contexts, focussing on the recognition of essential DNA-protein interactions. They will have the opportunity to undertake secondments at Sorbonne University, IBEC and Bruker Nano in Berlin, supported by a generous training budget. If you’re interested in this project, please get in touch with Alice.

In addition to their scientific education, this new generation of researchers will receive training in complementary skills to prepare them for the research job market. They will participate in training sessions on data management, open science, scientific communication, intellectual property rights and entrepreneurship.

For more information, please check out the press release from IBEC here.

Genomics to Whole Cell Conference Hosted in Sheffield

Marina attended the Genomics to Whole Cell workshop in Sheffield, a three-day event that brought together leading experts from the genomics, whole-cell, and modelling communities. As a first-year PhD student, Marina found the workshop to be a unique opportunity to observe how researchers from diverse fields collaborate to tackle complex scientific questions. It was inspiring and enlightening for her to see how ideas from different fields work together to solve shared challenges.

The workshop focused on current challenges and emerging opportunities in biological research, with a particular emphasis on advancements in AI. What stood out to Marina was the distinctive structure of the event. Unlike traditional conferences, the workshop focused on group discussions instead of lectures and presentations. Participants were divided into small groups and given specific questions to explore, covering topics such as automation, AI, data standards, and multi-model simulations for whole-cell modelling. This interactive format fostered deeper conversations and encouraged collaborative problem-solving.

For Marina, the highlight of the workshop was the strong collaboration across disciplines and the diversity of expertise among attendees. As someone at the beginning of her research journey, she found it incredibly motivating to witness the power of collective problem-solving and open dialogue.

Marina reflected on the workshop, saying, “Overall, the workshop left me feeling energised and inspired. The cross-disciplinary collaboration was a reminder of the importance of working together across fields to tackle the most challenging questions in science. This experience has given me valuable insights and a greater appreciation for the collaborative nature of research, which I look forward to applying in my PhD work.”

A Look Back at Our Trip to the I2K Conference in Milan!

We’re thrilled to share some highlights from our recent trip to a misty Milan for the Images 2 Knowledge conference! The conference was a fantastic opportunity to connect with passionate minds across the microscopy and data science communities and to see first-hand how work in image analysis is creating real interest and impact in the biological community.

Laura, Tom, Harriet and Max kicked off the event with excitement, especially knowing we had a workshop and live demo on deck! With some last-minute pull requests to tidy our outputs, we were prepared, if a bit nervous, to dive right into the capabilities of TopoStats. The workshop went off without a hitch and it was interesting to see the priorities of the wider image analysis community on using such a tool. There was particularly lively discussion about the participants loves, improvements, and future directions after seeing and using the tool for themselves, and how they would use the tool for their upcoming AFM data.

One of the most exciting moments was showcasing our AFMReader library (https://github.com/AFM-SPM/AFMReader/) in our workshop. We designed this to open-up the atomic force microscopy (AFM) community to use the tools developed by the wider microscopy image analysis world through Python. AFMReader provides essential tools for handling and analysing data specifically from AFM images, and it’s all built to be fully open and FAIR: Findable, Accessible, Interoperable, and Reusable. We were blown away by the response! The attendees were excited about how AFMReader could help them build their own pipelines and open their data up to the wealth of image analysis tools already being used by other microscopies.

In addition to our workshop, Laura present a fantastic flash talk highlight all of the amazing work our team does using TopoStats, and Max presented a beautiful poster showcasing his work developing deep learning methods for TopoStats!

Paper on kinetoplast DNA published in PCCP

Our former master’s student Bradley has published a paper from the work he carried out in our lab. “Multiscale topological analysis of kinetoplast DNA via high-resolution AFM” combined high-resolution AFM with a custom image analysis pipeline built in TopoStats to understand more about the topology of these unusual DNA structures. The work was carried out in collaboration with Patrick Doyle and Indresh Yadav from MIT, and was included as part of the PCCP Emerging Investigators collection, which highlights the excellent research done by Alice and the lab. 

Read more about the work here

UK & Ireland Single-Molecule Biology Meeting in London

On May 14-15, Alice, Libby and Slyvia travelled down to the MRC Laboratory of Medical Sciences at Imperial College London to attend the LUMICKS single-molecule research symposium. The two days consisted of a variety of wonderful talks, highlighting the importance of single-molecule techniques in biophysical research.

During the symposium, Alice gave an exciting talk entitled “Single molecule insights into how DNA supercoiling affects its interactions”, which was incredibly well received. In addition, Libby and Sylvia both gave flash talks and poster presentations talking about their current research during their PhD’s.

Alice giving her talk during the second day of the symposium.

The keynote speakers, Nynke Dekker and Simon Boulton both gave exceptionally stimulating talks on their research careers. As a PhD student, it was incredibly inspiring and motivating to watch. Two talk highlights were Lori Passmore who gave a talk on “insights into how the FANCD2-FANCI DNA repair clamp interacts with DNA” and Graeme King for “Probing the structure and interactions of negatively supercoiled DNA using optical tweezers and fluorescence imaging”. As a lab who’s main focus is singe-molecule imaging of DNA-protein interactions in solution, and the automation of analysis of these complexes, both these talks were very insightful into this field.

Thank you to David Rueda and Mina Brett-Pitt for organising this wonderful event!

Experience of a Master's Student: Bradley Diggines

Every year we welcome undergraduate and masters’ students with a variety of backgrounds to undertake a research project in our lab.

What was your project about and what did it involve?

I was characterising the structure of kinetoplast DNA (a large network of interconnected DNA minicircles using atomic force microscopy and novel image analysis procedures. The project therefore had an even split of lab time, working on the Bruker Icon AFM, and programming, which built upon the TopoStats software.

What did you learn from your time in the lab?

I learnt a whole range of skills, both within the lab (I had never even used a pipette before!), to the computational programming side. As a materials science undergrad, these skills allowed me to transition into a more biological-chemical space. Alice also gave great feedback on my written/presented work which was very valuable.

What was the highlight/the best part about your time in the lab?

I particularly enjoyed using the AFM itself! While frustrating at times, when I finally saw new images appearing on the screen it was very satisfying. Generally, the lab was also a fun and supportive environment, with everyone willing to help out when needed :)

What are you doing now/any future plans?

I’m now a PhD student at Imperial College London, working on automated high-throughput microfluidic systems for the development of novel lipid nanoparticles and artificial cells. This work is in collaboration with AstraZeneca UK, aiming to transfect typically “difficult to transfect cells” within their pipeline. Supervised by Dr Yuval Elani, Prof Dame Molly Stevens and Dr Nick Brooks.

Good luck Bradley!

The Power of AFM: AFM & SPM Meeting 2024

In March, the team visited the quaint city of Durham and attended the AFM & SPM Meeting 2024.

We started the exciting week off with a graduate school where we gained hands on experience on AFMs from various companies, a brilliant way to gain insight on the capabilities and advancements in AFM technology, in addition to lectures on the statistics for data analysis. The main conference revolved around AFM and SPM, covering a wide range of topics in Life and Biological Sciences, Materials Sciences and Energy, and Hardware, Software and Data Analysis. 

During the session on Life and Biological Sciences, Tom gave his talk titled “Determining DNA Damage by Atomic Force Microscopy”, providing insight on how powerful combining AFM with TopoStats, our program for automated tracing of biomolecules from AFM images, can be for advancing DNA topology research. His talk generated lots of interest from the audience!

Tom speaking at the Life and Biological Sciences session on “Determining DNA Damage by Atomic Force Microscopy”

Along with Tom’s talk, we had the privilege of attending numerous talks that captivated our attention with their thought-provoking content. We found ourselves deeply engaged and inspired by the diverse range of topics that were covered, leaving each of us with new ideas and perspectives to ponder. Amongst the speakers was Wei Feng Xue who performed structural analysis of helical filaments using three-dimensional contact point reconstruction AFM and Paolo Actis who demonstrated how AFM can be used for single molecule delivery into living cells.

We finished the days off with a poster session that bridged researchers from various fields, enabling us all to engage in in-depth discussions and broaden our knowledge on the potential of AFM in a plethora of research fields. During these sessions, Libby, Sylvia, Tobi and Laura were able to present their research to the community, allowing them to exchange insight with other researchers and provoke fruitful discussions on their respective research projects. 

It came as no surprise during the conference dinner when Sylvia and Libby were awarded the 1st and 3rd prize, respectively, for their outstanding poster presentations, a well-deserved recognition from their peers and the judging panel.

Sylvia (left) and Libby (right) awarded with the 1st and 3rd poster prizes, respectively.

The conference was both enjoyable and enlightening. Engaging with cutting-edge research, networking with fellow researchers and participating in thought-provoking conversations have enriched our understanding and inspired our research moving forward.

Max tackles the topographically complex mountains of banff with topology 2024

In March, Max visited the Rocky Mountains of Banff national park to attend the 2024: The Crossroads of Topology, Combinatorics and Biosciences: Deciphering the Entanglement of Multi-Stranded Nucleic Acids workshop

Max giving his presentation on new image analysis methods to characterise DNA Topology

Set within the heart of the Banff national park, this 5-day conference brought together researchers from a range of fields to remove our blinders and open our eyes to the multitude of research attacking the same topological problems from various angles. From hardcore mathematical modellers developing language models to probe the intricacies RNA structures, to the dedicated biologists investigating ion interactions on  and computational modellers, this workshop was a great opportunity to merge these fields and push the understanding of DNA topology.

At the workshop, I heard some truly amazing talks surrounding the multitude of DNA structures in various environments, and how this structure can regulate access to the genome, as well as insight into the models and physical laws used to govern them. Standout talks include Lynn Zechiedrich showing negative supercoiling induced DNA-protein interactions occur at a supercoiling threshold, alongside fruitful results surrounding supercoiling induced defects from a past collaboration with Alice. I was also intrigued by Andrew Rechnitzer research into streamlining pivot algorithms to quickly model complex knot and catenated lattice. I also wanted to shout out the superb talk given by Lila Kari where she used machine learning to identify clusters of taxonomic and environmental factors from fragmented DNA sequences of various species.

Group photo of conference attendees

There were many insightful discussions to highlight the biological questions faced by the community such as how does DNA packing affect genome access? It gave a chance for people to spotlight their research which pushed towards this goal, and discussed the ways in which the expertise from these different fields could be utilised to move together towards the biological answers we seek via developing collaborations.

*Most talks should be available on the BIRS website here

As part of the Cellphe team, Laura won one of the University of York's ECR Open Research awards

We are delighted to reveal that Laura has won the Open Research award for the development of CellPhe, a user-friendly free open research tool to help better understand cell mutation and resistance in cancer. This award recognises the overall impact of CellPhe as open-source software in the field of biology and the bright future ahead for automation in microscopical data analysis, as well as the undeniable hard work of the CellPhe team!

Read more about CellPhe here

Pyne lab wins poster awards at the AFM & SPM Meeting 2024

We are incredibly pleased to announce that Sylvia and Libby from our lab won the first and third poster prizes, respectively, at the AFM & SPM Meeting in Durham, March 2024. Thank you for to the organisers for such a wonderful event, and this was the cherry on the cake! We had a truly brilliant time at this event, meeting fellow microscopists and exchanging research. We look forward to future events!

Team TopoStats wins The Open Research Prize 2023

We are pleased to announce that our team won the award for Open Research 2023! We won this award for our work on TopoStats, which is an open source software tool used to automate editing, analysis and quantification of data obtained from Atomic Force Microscopy. The aim of our software is to aid the field in moving away from manual analysis processes which have low throughput and rely on experience researchers. Our current focus is on developing new image analysis functionality for TopoStats to accelerate the development of novel therapies and improve our understanding of health and disease.

Read more about the award here

Alice Pyne wins the 2023 AFM and SPM award!

In July 2023, Alice won the very prestigious AFM and SPM award presented by the Royal Microscopical Society. Alice has been an independent fellow since 2017 and has been at the University of Sheffield since 2019. Since starting her lab, she has taken the AFM field by storm whilst working closely with industry to develop new AFM methods, enabling us to observe the double helix of DNA at and conduct intricate experiments observing DNA-protein interactions. We’re all very proud of her!

Read about Alice’s award here!

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UK SPM/AFM Users Meeting 2024

In January 2024, the lab attended the Bruker UK SPM/AFM Users Meeting 2024. It was a privilege to attend the event which was held at the Henry Royce Institute in Manchester. The days were split into two with demonstrations of incredible microscope technology in the morning followed by an afternoon of fascinating, frontier pushing science. As single molecule, bio-AFM users it was particularly interesting to hear about developments in other SPM technologies. For example, AFM-IR which allows the operator to gather information about their sample surface as well as infrared spectra helping identify the materials it contains and it was intriguing to think about how this could be applied to our work.

Two standout talks came from our very own Max Gamill, who described recent advances in TopoStats’ ability to resolve topology from AFM images and Dr Laia Pasquina Lemonche, who discussed her work developing software to study bacteria with the aim of developing new antibiotics, which was thought provoking and very exciting.

In the evening, we attended a meal where it was an absolute pleasure to listen to Dr Alex Ramadan tell the story of her journey to academia. The food was amazing and one of the highlights of the evening was the AFM quiz, which caused an unexpected explosion of competitiveness between tables. 

Alice presenting our work on automating tracking and tracing of DNA

Overall, the conference was a blend of mind -blowing science and discussions with enthusiastic microscopists! We’re looking forward to next years event.

Taking AFM to the Alps- EMBO DNA Topology Workshop

In September, Max, Libby, Eddie, Tom, and Alice visited the picturesque Swiss village of Villars-sur-Ollon to attend the 2023 EMBO DNA topology and topoisomerases in genome dynamics workshop. 

Set against the beautiful backdrop of the Alps, we first attended an LS2 ECR satellite event (chaired by Alice) where Eddie, Libby, Max and Tom all gave a 5 minute flash talk introducing their research. This event also gave us all an opportunity to present our research and network with our fellow ECRs while getting to know the scenic setting for the conference. 

Max speaking at the ECR satellite events about his research using new image analysis methods to characterise DNA topology

The main conference featured fantastic talks covering the critical role of DNA topology in a wide range of processes, offering deep insights into its implications for transcription regulation, topoisomerase activity, as well as its impact on various aspects of disease progression and developmental biology. Standout talks included a captivating keynote by Tony Maxwell, delving into his personal journey in topoisomerase research. His insightful anecdotes and scientific contributions illuminated the evolution of this field. Additionally, Valerie Lamour delivered a compelling presentation on the binding mechanisms of DNA gyrase to supercoiled DNA and its implications in DNA biology.

During the Regulation of DNA Topology and Topoisomerase Activity session, Alice delivered her talk titled "Tackling Topology with TopoStats." It was well reived by the audience and provoked interesting questions and lead to lots of discussion in the coffee sessions and at dinners that followed.
The poster sessions saw Max, Libby, Eddie, and Tom showcase their work which inspired lots of thought-provoking questions about the potential of AFM and advanced image analysis techniques in DNA topology research and led to productive discussions about future work and collaboration.

Alice speaking at the main workshop on “Tackling Topology with TopoStats”

The trip allowed the those of us attending from the Pyne group to reflect on our research within the broader context of the field and plan the upcoming stages of our research. The conference provided an invaluable platform for networking and engaging in in-depth discussions on our research in DNA topology, bringing together researchers at different career stages from across the field. The anticipation is that these discussions will pave the way for fruitful research and collaborations in the future.

Eddie (top left), Max (top right), Tom (bottom left) and Libby (bottom right) presenting their posters at the main conference poster session.