Latest updatesNobel Prize in Chemistry awarded for development of cryoEM
Today the revolutionary impact of cryo-electron microscopy on our understanding of fundamental life processes has been recognized through the announcement of the 2017 Nobel Prize in Chemistry.
The prize has been awarded to Richard Henderson (MRC Cambridge), Jacques Dubochet (University of Lausanne) and Joachim Frank (Columbia University) "for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution”. Cryo-electron microcopy (CryoEM) is one of the techniques that is fundamental to our Imagine: imaging life programme. CryoEM has allowed us to visualise biochemical processes in unprecedented detail; in the words of the Nobel organisation, in a way “which is decisive for both the basic understanding of life’s chemistry and for the development of pharmaceuticals.” Our work in Imagine builds directly on the methods first pioneered by Henderson, Dubochet, Frank and others, starting in the 1970s and 1980s. It is an especially exciting day for one of our Imagine team, Per Bullough, who was a student in the Henderson lab in the 1980s and witnessed many of the early developments taking shape. For more information on the science and scientists involved, go to: https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2017/press.html Microbe Safari
Our Florey and Imagine scientists held a public engagement event in the Winter Garden (Sheffield, S1 2LH) last weekend (16-17 September 2017), under the giant inflatable E.coli.
With lots of fun, interactive activities on offer, it provided the perfect opportunity for members of the public to learn more about bacteria, infectious disease and the work we do at the University of Sheffield. To show the diversity, and beauty, of bacterial cultures, our scientists bought along agar plates containing lots of different types of bacteria. There was a microscopy exhibit where you could view bacteria down a microscope, find out how an atomic force microscope works and see 3D printed models of S.aureus cells. With these activities and more (including an opportunity for our younger visitors to ‘make a microbe’), it was lovely to meet so many people interested in our research. Thank you to everyone who volunteered their time to help out, and to everyone who visited our exhibits! See #MicrobeSafari for more images of the event! 
A very warm welcome to Dr Julien Bergeron who joined the university this week (July 2017) as a lecturer in the department of Molecular Biology and Biotechnology (MBB) for the IMAGINE:Imaging life project. Julien joins us from the University of Washington where he worked as a senior fellow.
Prof. Per Bullough (Imagine:Imaging Life) and Dr. Robert Fagan (Florey Institute) were recently (May 2017) awarded a £567,668 grant from the Biotechnology and Biological Sciences Research Council (BBSRC) to explore the “Structure and interactions of the Clostridium difficile S-layer with bacteriocins”. The project will use advanced imaging techniques to visualise the struture, including use of the new cryo-electron microscope funded through the Imagine programme.
Clostridium difficile (C. difficile) is the most frequent cause of hospital acquired infection across Europe; it is highly antibiotic resistant. There is an urgent clinical need for antimicrobials that kill C. difficile without disruption to other gut bacteria. This project aims to characterise the structure and interactions of the outermost surface of the bacterium with an innovative new type of therapeutic called an Avidocin. Avidocins are virus-like particles that target the outer surface of the bacterial cell to kill this important pathogen. 
Avidocin binding to the C. difficile S-layer
£1.2M to fight C. Difficile
Dr Robert Fagan (Department of Molecular Biology and Biotechnology and member of the Florey Institute) has been awarded a £1.2M Wellcome Trust Collaborative Award to study the hospital 'superbug' Clostridium difficile. This is a collaborative project with Dr Gillian Douce (University of Glasgow) and Dr Paula Salgado (Newcastle University). The bacterium is known to affect patients who have recently been treated with antibiotics. It can affect the bowel, causing severe diarrhoea and inflammation, and can easily spread to others.
Dr Fagan studies the C. difficile S-layer, a crystalline protein shell covering the surface of the bacterium. In previous studies, his research group has shown that the S-layer is crucial for pathogenicity, but little is known about how the bacteria assemble this crystal armour or how it contributes to disease. By working together with cutting-edge structural biologists in Newcastle and world leaders in C. difficile infection modelling in Glasgow, Dr Fagan and colleagues hope to find new ways of tackling this highly antibiotic-resistant bacterium in the clinic. Dr Fagan will use molecular biology techniques to determine the function of the S-layer in combination with high resolution microscopy techniques (Imagine:Imaging Life) to visualise its structure and organisation in the cell. "By studying the C. difficile S-layer we hope to identify weaknesses in this superbug's armour and find new ways to fight infection. It is hugely exciting to be able to work at the interface of different scientific disciplines, combining our expertise to make advances that just wouldn't be possible working in isolation." 
C. difficile cell envelope showing the S-layer
Welcome to Dr Moumita Dutta
JPK press release highlights our ongoing collaborative research
Dr Nic Mullin was recently (07 Mar 17) featured in a press release from JPK systems. The article highlighted his ongoing collaboration on instrument development, specifically with JPK’s NanoWizard® AFM systems, and how his research fits within the Imagine initiative. The article also showcased the correlative work carried out in Sheffield, in particular the use of one of our JPK AFM systems for correlative AFM-STORM.
‘As well as applying existing methods and instrumentation, the group have the added challenge to develop new equipment and protocols to allow the study of different samples at higher magnifications applying new detection systems. This has been formalised (for biological systems) in the Imagine: Imaging Life initiative, which brings together electron microscopy, super-resolution optical microscopy and AFM to study living systems. One of the major goals is to use AFM to provide information that complements the information garnered from the electron and super-resolution optical microscopies’. Welcome to Dr Buddhapriya Chakrabarti
He is a modeller who aims to work closely with the IMAGINE team, using results of super-resolution microscopy images to construct physical models of biological systems that are amenable to mathematical analysis. These would provide a quantitative and mechanistic understanding of biophysical systems of interest.
His principal areas of research in Biophysics focus on DNA and protein mechanics, statistical mechanics of gene regulatory networks and chromatin packing and understanding mechanics of viruses. Imagine:Imaging Life launch symposium
Thank you to everyone who joined us for our launch symposium last week (12-13 January 2017). The launch was a celebration of our progress and successes to date; namely recruitment of staff and a cohort of PhD students, refurbishment of the three core microscopy facilities (the Wolfson Light Microscopy Facility, the Faculty of Science Electron Microscopy (EM) Centre and the Biophysical Imaging Centre (BICEN)) and investment in state-of-the-art microscopes, including a £2M cryo electron microscope.
With our unique focus on biological imaging using super-resolution microscopy, electron microscopy AND atomic force microscopy, the symposium had wide appeal, attracting 140 delegates from life sciences, physics and engineering. The symposium was held over two days; with a poster competition, drinks reception, laboratory tours and conference dinner on the first day. The calibre of the talks was exceptional, with speakers highlighting current advances, as well as the utility of different advanced microscopy techniques in diverse biological fields (from prokaryotic cells to plants). The keynotes were given by Jie Xiao (Johns Hopkins University) and Jennifer Lippincott-Schwartz (Howard Hughes Medical Institute, Janelia Research Campus), renowned leaders in the field of cell biology, and pioneers in the use of optical super resolution microscopy who gave fascinating insights into novel approaches that are being developed in their labs. We were extraordinarily fortunate to have received funding from the Company of Biologists, the EPSRC (through the Sheffield Antimicrobial Resistance network) and microscopy companies (Nikon, FEI, JPK, Hamamatsu, Zeiss, Oxford Nanoimaging Ltd, Andor and Agar Scientific). A big thank you for supporting our launch symposium! 
Thank you also to everyone who sent us feedback after the event (see below for some examples). We've been absolutely delighted to receive such positive feedback!
'The Imagine Launch Symposium was hugely enjoyable. The presentations were individually comparable in quality to the best I've ever experienced. More than that however, the programme as a whole was better than any conference I've attended in the last 5 years. In addition to the enormously enjoyable scientific programme, the logistical details were so well organised as to be invisible. Overall a fantastic event and a very exciting launch for the new Futures 2022 project'.
Exercising restraint: how growing slower can allow bacteria to dominate
In the microbial world rapid growth has long been thought to be the key to success. However, new research published this week by William Durham (http://mackdurham.group.shef.ac.uk/) shows that in porous environments, such as within soil, sediments, and rock, microbes such as bacteria can actually gain a competitive advantage by growing more slowly. Since more than 95% of bacteria on Earth live in these porous habitats, this new work provides new tools to understand how natural bacterial communities function, as well to engineer them for important functions, like cleaning up polluted drinking water or enhancing oil extraction.
In typical laboratory conditions, cells that grow more rapidly dominate over those that grow more slowly, however these findings suggest that this concept does not always hold within more natural porous habitats, where cells rely on fluid flow to supply them with nutrients. Dr Durham explained, “In porous environments most bacteria live attached to the surfaces of soil and rock, where they form communities called biofilms. It is incredibly hard to visualize how biofilms growing in these opaque environments affect patterns of flow, so we boiled this problem down to a much simpler model that still captures the fundamental physics. We found that bacteria living in porous substrates face a fundamental challenge: they need to reproduce but not so fast that they divert the flow that nourishes them.” Durham began this project while working at University of Oxford and led a multidisciplinary team to develop experiments and mathematical models of competition between bacteria that grow at different rates. They found that when the rate at which flow travels through a porous environment is large, faster growing biofilms have the competitive advantage, as previously predicted. However, when flow was relatively weak, fast growing biofilms divert their nutrient supply to slower growing bacteria, allowing the latter to gain the upper hand. This seemingly paradoxical result stems from the fact that flow always takes the path of least resistance: when fast growing cells begin to divert flow, it reduces the rate at which they detach from the surface, which then causes them to further increase their resistance to flow. This positive feedback ultimately leads to the fast growing bacteria fully blocking their supply of nutrients: they bite the hand that feeds them. The predictions of Durham and his international team of collaborators may ultimately allow us to better engineer bacterial communities to perform important functions. This study found that while strong and weak flow favour fast and slow growing bacteria respectively, intermediate rates of flow allow cells with different growth rates to maintain access to flow over long periods. In many situations, such the clean-up of harmful chemicals within porous reactors, maintaining diverse assemblages of bacteria that grow at different rates allows them more efficiently degrade harmful compounds. On the other hand, bacterial biofilms are also used to stifle the spread of pollutants that have spilled into the water table: in such situations it is clearly advantageous to design bacterial communities that block their pore spaces to inhibit flow that can spread contaminants to wells that supply drinking water. This project was funded by the Engineering and Physical Sciences Research Council, the European Research Council and the Human Frontier Science Program, and was published this week in the Proceedings of the National Academy of Sciences (USA). 
Figure: Two different types of bacteria, one labelled red and the other green, compete in a microfluidic device that simulates soil (credit: Katharine Coyle, Roman Stocker, and William Durham).
Egbert Hoiczyk gives talk as part of iGem Sheffield Edu day
Egbert Hoiczyk recently gave a lecture on 'The Power of Synthetic Biology' to 40 school children from three local schools as part of the iGEM Sheffield Edu day (19 Oct 16). This was followed by a science fair and a group based activity where pupils had the opportunity to design a product that uses the principles of synthetic biology to address a particular problem. The International Genetically Engineered Machine (iGEM) foundation is an independent, non-profit organisation that focuses on education and competition, using synthetic biology to solve problems and make a positive contribution to communities and/or the world. The iGEM Sheffield team will be travelling to Boston on 27th October to compete at The Massachusetts Institute of Technology (MIT) - the final of the competition will take place on Friday 28th October. William Durham presents at EuroScience Open Forum
New Imagine recruit, Dr William Durham, recently delivered an invited presentation at the EuroScience Open Forum (ESOF) in a session on antibiotic resistance. His talk highlighted recent work by his group that shows that bacteria in surface attached biofilms can actively sense and navigate chemical gradients by pulling themselves along using tiny "grappling hooks” called pili. Because biofilms are strongly associated with antibiotic resistance, this discovery offers new way to manipulate and potentially disrupt recalcitrant clinical infections. His session was organized by the European Research Council.
Christa Walther selected to attend first NEUBIAS training course
The new Network of European BioImage Analysts to advance life science imaging (NEUBIAS) is organising its first BioImage Analysis Training School for BioImaging Facilities this September (2016). The program will include computational methods and tools for analysing images of molecules, cells and tissues, tailored for staff scientists working in microscopy facilities, who can then provide support and training for researchers who have an immediate need to deploy image analysis in their research. BioImage Analyst are specialised in customising image analysis workflows by assembling and automating multiple computational tools, and by interacting with Software developers and Life Scientists to facilitate image analysis.
We are delighted that our Senior Experimental Officer for Super-resolution Microscopy, Dr Christa Walther has been accepted onto this course. We are sure this will further enhance the opportunities we can offer with respect to innovative imaging within the Imagine project.
Imaging Life 2016
The winning image competition entries from Imaging Life 2016
KrebsFest is 'highly commended' at industry awards
Congratulations to the Public Engagement and Impact team who were highly commended in the Public Engagement and Advocacy category at the Association of Research Managers and Administrators (ARMA) awards held last night (Tuesday 7 June 2016), for the hugely successful project, KrebsFest which celebrated the life and work of our Nobel Prize winning academic Sir Hans Krebs.
http://www.sheffield.ac.uk/staff/news/krebsfest-award-1.581541 "This nomination is thoroughly deserved. The advice, guidance and support the team provided for KrebsFest was invaluable to the overall success and delivery of the festival".
“The human body regularly fights bacteria without any problems. This is because blood cells circulating in our immune system, called macrophages and neutrophils, fight the first signs of infection in the body by recognising and destroying the bacteria. This project seeks to increase our understanding of exactly how these immune cells work so that we can maximise the ability of the cells to not only destroy harmful bacteria but also limit the damage to healthy tissue caused by excessive inflammation. If we can identify what genes within these cells are the most important in the optimal killing of bacteria, it could lead to medicines being developed that can re-engage and enhance this vital process when it fails.” The funding is part of a £9.5M funding package announced today (Thursday 19 May 2016) by the Medical Research Council (MRC) as part of a cross-council initiative to tackle antimicrobial resistance (AMR). The University of Bristol has received £2.2M for a project looking at the potential to develop new types of antibiotics from fungi and the University of Leeds has been awarded £3.8M to develop a new tool that can be used by doctors to detect the presence of a bacterial or viral infection quickly before antibiotics are prescribed to stop their unnecessary use. The awards together mark one of the biggest investments into AMR since the initiative launched and will use new technology to exploit natural compounds, develop a tool to offer better and faster diagnostics and explore how the body’s own immune system can be boosted to fight infection.
The world is facing an increase in the number and type of bacteria resistant to antibiotics alongside stagnation in the development of new antibiotics or viable alternatives. It is clear that an interdisciplinary approach at a global level is needed to tackle the challenge in order to save millions of lives being lost as a result of antibiotic-resistant bacteria. The MRC has been working with the other research councils that form Research Councils UK to identify research opportunities that cross disciplines to help tackle the rise in AMR. The latest round of awards have been funded by the MRC, Biotechnology and Biological Sciences Research Council (BBSRC), Economic and Physical Social Research Council (EPSRC) and Economic and Social Research Council (ESRC) through the AMR cross-council initiative, as part of a strategic and co-ordinated effort to address the growing problem head on. Super-resolution publication
Data from our newly installed N-STORM (Nikon) super resolution microscope in the Light Microscope Facility has been published in Genetics by our colleagues in the Bateson Centre and the Department of Biomedical Sciences. Pooranachandran N and Malicki JJ. Unexpected Roles for Ciliary Kinesins and Intraflagellar Transport Proteins. Genetics. 2016; 115.180943 Imagine PhD student to present at SGM conference
Imagine PhD student, Viralkumar Panchal, is currently in his second year and works in Simon Foster's lab. In a few days (21–24 March) he will have the opportunity to present his work at the SGM conference in Liverpool. Viral writes - "The Society of General Microbiology (SGM) conference 2016 will be of immense benefit to me. I am working on how methicillin-resistant Staphylococcus aureus (MRSA) manages to be so resistant to beta-lactam antibiotics (such as methicillin) by studying the acquired penicillin binding protein (PBP2A). My work is of direct relevance to the conference and will be presented as a poster. The conference will also give me an opportunity to take part in the Prokaryotic Cell Biology Forum and the Genetics Forum as well as attend the symposia" Launch of our seminar series – a new initiative for 2016!
We launched our seminar series on 1st March with a fascinating and well attended seminar by Prof John Rodenburg (University of Sheffield), on ptychography. Ptychography (the ‘p’ is silent) is a novel imaging technique that can retrieve the phase information from multiple intensity diffraction patterns, and can therefore be used to visualise changes in refraction indices. Amazingly, this technique can be performed with visible light, as well as x-rays or electrons, without any lenses and as the technique does not use stains or dyes, it can be used for high contrast imaging of live cell cultures. A big thank you to John for a wonderful and innovative start to our seminar series! Cancer Research UK multidisciplinary grant awarded
Congratulations to Professor Nicola Brown, Department of Oncology & Metabolism, who with collaborators in Physics & Astronomy (Prof Jamie Hobbs, Imagine:Imaging Life) and Oral & Maxillofacial Pathology recently (Jan 16) received a grant of £476,000 from Cancer Research UK to study “Mechano-biology of the bone metastatic niche in breast cancer”. The Cancer Research UK Multidisciplinary Project Awards support collaborations between cancer researchers and scientists from engineering/physical science disciplines. The funded project will combine biological, mechanical and theoretical physics modelling approaches to characterise the mechano-biological features of the bone microenvironment in breast cancer bone metastasis and the effects of cancer agents on these properties with respect to disease progression. http://medicine.dept.shef.ac.uk/news/index.php/2016/01/21/cancer-research-uk-award/
Ever wanted to take a tour inside a protein?
Well, KrebsFest offered just that! Jeffery So, one of our first year PGR students was a member of the Atom-Labs team, led by Dr. Claudine Bisson during KrebsFest. They exhibited in the Winter Garden and in Firth Hall (at The University of Sheffield) on the public open evenings. The event was aimed at everyone, from primary school children to adults. The theme was Exploring Protein Structure in 3D, and Machines In Miniature. With virtual reality headsets, guests could take a tour inside a protein or DNA molecule. There were also opportunities to have a go at crystallising proteins, and learn why X-ray crystallography and the understanding of protein structure is so important. Thank you KrebsFest!
Glow stick battles between bacteria and antibiotics projected onto the inner courtyard at Firth court, walking on custard and controlling model racing cars with only your brain waves – it can only be KrebsFest! These were just a small selection of activities on offer at the KrebsFest open night (07 Nov 15) and the public night (13 Nov 15). Other gems included an amazing rap by Oort Kuiper, dance performances by The Balbir Singh Dance Company and (of course!) the 28m inflatable E.Coli hanging from the ceiling in Firth Hall. Many congrats to the organisers - it's been an amazing festival!
Per Bullough presents at Bacillus conference in New Delhi
Last week (30 Oct 15), Prof. Per Bullough presented on recent findings in the assembly of endospore coats at the 7th International Conference on Bacillus anthracis, B. cereus & B. thuringiensis in New Delhi, India (http://www.bacillusact2015.org/index.php). Endospores are dormant survival structures that some species of bacteria can form in response to stress.
Sculptures unveiled in the Winter Gardens as part of KrebsFest
A giant inflatable E.Coli created by artist Luke Jerram has been unveiled in the Winter Gardens in Sheffield City Centre today (15 Oct 15). The sculpure, which is an amazing 90 feet long, has been hung from the ceiling to celebrate the work of scientist Sir Hans Krebs as part of KrebsFest. Also on display is an origami sculpture of green fluorescent protein (GFP) made from over 10,000 pieces of folded paper made by Sheffield-based artist Seiko Kinoshita. http://www.bbc.co.uk/news/uk-england-south-yorkshire-34530038
Many congratulations to the IMAGINE PGR students for organising and hosting an excellent symposium on Friday (18 Sep 15). The one day conference, held at the University of Sheffield, boasted an exciting programme with updates on the latest technological advances in imaging techniques and examples of how these techiques are being used to try and answer challenging questions in the field of biology. Whether your field of expertise was electron microscopy, super-resolution light microscopy or atomic force microscopy, there was something for everyone - well done guys!
"It has been a great experience organising the first Imagine event, learned a lot. I feel wonderful to be in the midst of great minds and people with multidisciplinary background" Viralkumar Panchal
"Imaging Life was a hit! Great talks, great participation and lots of great science. We hope we succeeded in bringing lots of ideas together and we look forward to doing it all again next year!" Tania Mendonca Congratulations also to all the prize winners. Felix Weihs (University of Sheffield) won first prize in the poster competition for his poster entitled 'A supramolecular pattern in the membrane of Staphylococcus aureus'. Second prize went to R Maiti for 'Skin surface and sub-surface strain and deformation imaging' and third prize went to Chloe Dickinson for 'Imaging the 3D structure of Arabidopsis thaliana roots using Digital Holography'.
In the 'people's vote' image competition, Sofia Granados (Univeristy of Sheffield) won first prize with her image of 'Signals in the ovary'. Second prize went to Basudha Basu and Dharaminder Singh won third prize.
Welcome also to Dr Ling Chin Hwang
Welcome to Dr Egbert Hoiczyk
Egbert joined the university in April (2015) as a senior lecturer for the IMAGINE:Imaging life project.
He writes - Recent advances in high-resolution microscopy, bioinformatics, and structure determination have resulted in a fundamental reassessment of the organization of bacterial cells. Once perceived as simple and unorganized, bacteria have become appreciated in recent years for possessing structural, spatial and temporal organizations that rival that of eukaryotic cells. Through a combination of advanced microscopy and classical genetics, biochemistry, and physiology I aim at understanding how this complex organization is achieved and maintained in cells. Two different approaches are used to accomplish this goal. The first approach relies on the fractionation of cells with the goal to discover, isolate, and characterize novel sub-complexes and organelles that form the elementary building blocks of bacterial cells, while the second approach uses live imaging techniques and electron tomography to study the function and dynamics of these structures in the context of living cells. https://www.sheffield.ac.uk/mbb/staff/egberthoiczyk/egberthoiczyk 
Sheffield leads new networking EPSRC award 28 May 2015
Prof. Jamie Hobbs was recently awarded a £509,648 grant from the Engineering and Physical Sciences Research Council (EPSRC) to facilitate engineering and physical sciences involvement with the antimicrobial resistance (AMR) problem. The Sheffield antimicrobial resistance network (SHAMROK) grant will enable new, and augment existing, research opportunities by developing cross faculty networks within our internationally leading IMAGINE:Imaging Life and Florey Institutes. The network will focus on the development of physical and physicochemical tools for understanding bacteriology and the host response, the development of new surfaces, dressings, and tissue engineering related approaches for preventing infections and improved drug delivery strategies for antimicrobials. The interdisciplinary approach shall make the most of our existing expertise to catalyse truly transformative activities that are unconstrained by traditional discipline boundaries. Read more http://gow.epsrc.ac.uk/NGBOViewGrant.aspx?GrantRef=EP/M027430/1 http://gtr.rcuk.ac.uk/project/A5A511D8-DFE2-4588-8556-ED661BFD6AA2 Sheffield part of winning consortium to tackle AMR 28 May 2015 The Medical Research Council (MRC) led cross-council initiative to tackle antimicrobial resistance (AMR) has awarded £3.19 million to the SWON alliance (a multi-partner collaboration between the Universities of Sheffield, Newcastle and Oxford, led by the University of Warwick). The grant aims to tackle AMR by elucidating the fundamental processes of bacterial cell wall synthesis. By funding research into how the cell wall can be targeted by new antibiotics we aim to understand how resistance to antibiotics occurs. The University of Sheffield shall use the IMAGINE infrastructure and our expertise in Staphylococcus aureus (Florey Institute) to analyse how the cell wall is made and how antibiotics can inhibit this process. Read more http://www.mrc.ac.uk/news-events/news/5million-boost-to-superbug-researchers/ http://www.mrc.ac.uk/research/spotlights/antimicrobial-resistance/ |
