The Fagan Lab
We are the Clostridial Cell Biology Group at the University of Sheffield. We study all aspects of cell biology, including the architecture and biogenesis of surface structures on both vegetative cells and spores. We are interested in how bacteriophage penetrate the cell envelope and how Clostridia can modify their envelope to develop resistance to both phage and antibiotics.
Lab news
The latest chapter in our work on C. difficile vancomycin resistance is now available on bioRxiv. This paper builds on the experimental evolution work done by Jess Buddle during her PhD. Working with MBiolSci student Vicky Pennington, Jess characterised the mechanism of resistance in evolved strain Bc2. They discovered that only two mutations were needed to recapitulate resistance - one of which affects a previously uncharacterised two-component system which we have named VnrRS.
A double confirmation review success to celebrate this month! This is the formal process at the end of the first year of study that confirms PhD candidate status and both Lilia and Conrad have passed with flying colours. Congratulations both!
Congratulations to Hannah on the publication of two new papers this month! The first is a collaboration with the Mesnage group looking at remodelling of the cell wall in Enterococcus faecalis and the impact this has on virulence - published this month in PLOS Pathogens. The second is a collaboration with the Rodrigues group at the University of Warwick looking at cell-cell signalling during Bacillus subtilis sporulation - published this month in PLOS Genetics.
We're at the 2nd iteration of the Cross-Channel C. difficile Forum in Newcastle and Lilia has done a fantastic job of her first flash poster presentation, introducing her PhD work on the C. difficile stringent response! On day 2 we also had a great presentation from Anirudh on genetic engineering of phage.
We like to keep our group meetings fairly informal so we can usually be found in one of our local cafes on a Friday morning. Today we were joined by lab alum Jess Buddle to discuss another paper coming from her PhD work on C. difficile vancomycin resistance. In our lab meetings we discuss upcoming conferences, papers and grant applications and do a quick roundtable so everyone knows what's going on in all of our current projects. The newest canine group member, Labrador puppy Pip, also came along this morning to meet everyone and catch up on the latest news on spore germination dynamics.
We were very well represented at the 11th European Spores Conference this week with fantastic talks from Anne and Abigail - hat tip to Per Bullough for the photos. Abigail also won a prize for her poster!
Jason's paper describing the cyro-EM structure of C. difficile phage phiCD508 has been published in Life Science Alliance. During his BBSRC-funded postdoc, Jason developed and optimised our pipeline for phage structural characterisation. He is now setting up his own independent research group (funded by a BBSRC Discovery Fellowship).
In the video on the left you can see the structural changes that occur in the sheath that lead to contraction of the phage tail.
Last week Abigail and Anne presented their work on C. sporogenes spore germination at Physics of Life 2025 in Harrogate. More to come at the 11th European Spores Conference in a couple of weeks time.
Congratulations Jess! After four years of incredibly hard work the new Dr Buddle has graduated today with a PhD in Microbiology. Jess's PhD started during the difficult early days of the Covid-19 pandemic when we were working shifts in the lab and socially distancing. Her work involved a huge experimental evolution in which she demonstrated how easily vancomycin resistance can emerge in a C. difficile clinical isolate. She developed bespoke bioinformatics pipelines to analyse the huge amount of genomics and transcriptomics data generated during the project and, in validating resistance conferring mutations, made over 60 C. difficile mutants. During her PhD Jess published a review on C. difficile virulence, contributed to an in-depth functional analysis of L,D-transpeptidases and finally published her huge vancomycin resistance evolution study. There's more to come but for now Jess has moved on to a PostDoc position in a fantastic lab in Sheffield.
It's December so that means it's time for our annual Peak District hike and Christmas meal. This year we were in and around the beautiful town of Hope and, despite the bad weather over the last couple of weeks, 18 brave souls managed the long hike before dinner. No comment on how many had falls in the mud! Christmas Dinner this year was in the charming Cheshire Cheese Inn, a beautiful family run pub that dates back to 1578!
We will shortly be advertising two fully funded PhD studentships - see our 'Join Us' page for more details. Both are focused on the infection of C. difficile by bacteriophage - one studying the evolutionary interplay between phage and host and how this is impacted by sporulation and the second applying cutting edge imaging technologies to understand the molecular basis of cell envelope penetration. If you have any questions please email Rob.
Our Friday morning group meeting is in our favourite local cafe, Elm. This morning we welcomed a bunch of new starters. Lilia starts her PhD this week - she'll be focusing on the C. difficile stringent response. Victoria and Isabel join us for their 6 month MBiolSci research projects. They'll both be working on our big vancomycin resistance project. Last but not least, Daisy is also doing her MBiolSci project, joint with Per Bullough and supervised by Hannah, working on spore germination. Welcome everyone! When Conrad and Abigail start we may need to find a new venue.
Huge congratulations to Dr Buddle (a.k.a. Jess!) who passed her PhD viva today with only minor corrections. By all account the viva was a fantastic end to a very successful PhD - thanks also to the wonderful examiners Dr Wiep Klaas Smits and Dr Rebecca Corrigan. Jess is with us for a few more weeks to finish up the next paper before moving to pastures new.
Ahead of the start of the new academic semester we spent a day in the beautiful Peak District town of Calver, talking about the process of funding our science and thinking about our longer term grant pipeline. Unfortunately not everyone could make it this time but we got to welcome Lilia to the group! Deteriorating weather scotched our plans for an afternoon hike so we instead retreated to the local pub to continue the scientific discussions.
Congratulations to Becky on winning the best talk prize at the School of Biosciences 3rd Year PhD Symposium! There were 41 presentations from our final year PhD students spread over two excellent days of science. Based on the wonderful research happening across the breadth of the Biosciences, the future of our disciplines are in safe hands.
Anne is at the Physics of Living Matter meeting in Marseille this week, presenting her work on the timing of transition events in spore germination. And of course no poster session is complete without a little colour-coordination!
Our paper describing the evolution of vancomycin resistance has been published in PLOS Biology! Congratulations to all involved and, in particular, to the dream team of Jess, Lucy and Anne. Jess put together a really nice explainer on Twitter:
At graduation today Rob received the MBB Teaching Prize. Huge thanks to everyone who voted!
Congratulations to Lilia and Lucy who both graduated with first class MBiolSci degrees today. Lucy did her MBiolSci project in our lab working on vancomycin resistance. She is second author on our soon to be published PLOS Biology paper and in October starts her PhD with the Grainger lab at the University of Birmingham. Lilia did her project with Prof Endre Kiss-Toth and starts her PhD in our lab in October - working on a collaborative project with Dr Rebecca Corrigan.
Congratulations to Anirudh on passing his confirmation review. This is the formal process at the end of the first year of study that confirms PhD candidate status.
Congratulations to Anirudh for winning the flash talk prize at UK Cellular Microbiology 2024!
Paper accepted! Congratulations all round but particularly to Jess on her first first author research paper and Lucy and Anne on their first paper. More to come once the paper is published...
Jess submitted her thesis!
A slightly different start to the week today. We went to the garden of our local pub, the University Arms, for some team-building axe throwing. A great way to relax and focus the mind and, of course, postdoc Hannah had to show us how it was done with some perfect 2-axe throws!
Jess, Anne and Rob attended the first cross-channel 3CdF meeting in Paris where Jess presented her work on C. difficile vancomycin resistance.
Becky was at the Microbiology Society conference in Edinburgh where she presented the work she carried out during her Professional Internship Placement (PIPs).
A very successful lab away day in the beautiful Peak District town of Calver. Lots of science, lots of dogs and lunch in the village local!
Our paper characterising the canonical L,D-transpeptidases in C. difficile has been published in JBC. This project is the work of lab alumni Nicola and Darren and was a collaborative MRC-funded project led by Steph Mesnage.
Another great Christmas hike and dinner in the Peak District. No snow this year - absolutely beautiful weather instead.
Anne presenting her first poster at the Physics of Living Matter meeting in Cambridge.
The 13th ClostPath meeting was held in the beautiful Banff and our group were very well-represented with talks from Hannah, Becky and Jess.
Jess's first major paper describing her PhD work on C. difficile vancomycin resistance is now available as a preprint on bioRxiv. Congratulations Jess!
Jason's paper describing the breathtaking cryoEM structure of the C. difficile phage phiCD508 is now available on bioRxiv.
Congratulations to Dr Fisher! The PhD is official now and, of course, Hannah needed a photo with the Don Whitley A35 and Ava the Arctica.
Our paper describing the importance of the C. difficile S-layer in the host is out now in PLoS Pathogens.
Becky won one of the Best Overall Poster prizes at our Faculty research showcase event. Congratulations!
In collaboration with Louis-Charles Fortier at the Université de Sherbrooke, we've demonstrated that the major S-layer protein SlpA is the main receptor for phage that infect C. difficile - just published in Microbiology Spectrum.
First conference talk for Becky!
Jess and Rob have written a review on C. difficile pathogenesis - just published in the journal Virulence.
We were joined by the Corrigan, Mesnage and Durham groups for a fantastic hike and Christmas lunch in the beautiful Peak District. We even had a little snow on the hills.
Very excited that Sheffield is hosting a Faraday Discussions meeting on Challenges in Biological cryo-electon microscopy. We even had Becky's first conference presentation - a flash talk.
Our work characterising phage endolysin CD16/50L has been published in Microbiology Spectrum. This paper, led by Sittinan Chanarat in Mahidol University, describes the meticulous work carried out by Bee (Wichuda) when she visited our lab during the last year of her PhD.
Becky and Jess were at the Microbiology Society conference in Dublin.
Congratulations to Dr Fernandez!
Our paper describing the structure of the C. difficile S-layer is finally out in Nature Communications. A project 17 years in the making...