The Florey Institute - News and Events

Day 10 - Using state of the art technology to image bacteria

18/3/2018

Using state of the art technology to image bacteria

Using cryo-electron microscopy in the Bergeron laboratory

My group use biophysical techniques to decipher the molecular details of large protein complexes involved in bacterial pathogenesis and antibiotic resistance. In particular, we are exploiting high-resolution cryo-electron microscopy (cryo-EM) for studying potential new antibiotics targets. In the past three years, cryo-EM has revolutionized our capacity to look at biological molecules at the level of individual atoms.

Specifically, we are studying the bacterial flagellum, a long rotating filament that acts as a propeller, allowing them to move and adhere on the surface of target cells. For pathogenic bacteria (such as E. coli, Salmonella and Yersinia), flagella can aid the spread of disease, and helps them attach to medical devices such as catheters. As a consequence, understanding the bacterial flagellum at the molecular level could have numerous medical implications, and disrupting its rotation and adherence properties could significantly reduce infection in a clinical setting. Because of its size and complexity, characterizing the flagellum at the molecular level was previously impossible. But with the recent advances of cryo-EM, we can now study this complex with unprecedented detail.

We are currently investigating the atomic details of the flagellum tip, to try and understand how it adheres onto human cells. We are also trying to decipher the architecture of the “basal body”, the region of the flagellum that is anchored at the bacterial surface and that acts as an anchoring point for its assembly. Ultimately, our research could be exploited to generate new antibiotics that block the formation or function of the flagellum.

Read more about Julien's research at: www.bergeronlab.com
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Day 9 - The Florey PhD experience

17/3/2018

A short Q&A asking one of our cohort about his experiences of doing a PhD

Haneesh, a PhD student with the Florey Institute, has taken the time to talk to us about his research project and how he has found doing a PhD in general!

What is the main focus of your research?
My main focus is developing novel chemical probes to image penicillin binding proteins (PBP’s) with the aim to elucidate their mechanisms in cell wall biosynthesis and role in antibiotic resistance. PBP’s are of high interest as we do not know how they have developed resistance to traditional β-lactam antibiotics such as penicillin, leading to highly resistant bacterial strains such as MRSA.

What implications does this have for your area?
Discerning the precise dynamics of PBP’s are of huge importance to gain insight into the major defence component of bacteria, the cell wall. Further understanding the biosynthesis of the cell wall will allow the effective design of future antibiotic drugs.

How have you found doing a PhD challenging/rewarding?
I enjoy learning new concepts on a regular basis and applying these to solve problems that I have in my work. Of course, not everything works first time (or second, or third!!) but that is to be expected in scientific research – overcoming these problems is what makes it so fun! Knowing that I am working on a critical part of healthcare is a big motivation for me and something which drives me on a daily basis. Being of a pure chemistry background, the biggest challenge for me has been to grasp the biology parts of my project. However, this has also been one of the most enjoyable aspects
as it’s given me the opportunity to be part of a wider multidisciplinary field which is becoming ever more important in tackling major healthcare challenges.

What would your top tip for prospective PhD students?
My top tip would be to have a healthy work-life balance during your PhD. A PhD is highly rewarding but also a lot of hard work so it’s important to keep your mind fresh. Do activities you enjoy outside of work on a regular basis, treat yourself, and take regular breaks during the year
(we all love a vacation! :) ).

Day 8 -Spotlight On: The Turner Lab

16/3/2018

Meet the members behind one of the Florey labs!

The Turner laboratory is a relatively new research group, headed by Dr. Claire Turner. Their research focuses predominantly on the Gram-positive bacterium Streptococcus pyogenes, also known as the Lancefield Group A Streptococcus (GAS).

S. pyogenes is capable of causing a diverse range of clinical syndromes. These include the relatively superficial i.e. pharyngitis (‘strep throat’), cellulitis and scarlet fever, but also potentially lethal infections such as necrotising fasciitis and streptococcal toxic shock syndrome. S. pyogenes is responsible for approximately c. 700 million infections each year globally, with c. 500,000 deaths.

Dr. Claire Turner

“My research implements a combination of whole genome sequencing, epidemiology, clinical analysis and phenotypic techniques to elucidate the various mechanisms by which S. pyogenes is able to cause disease, both at the molecular level and at the population level.”

Claire is a Royal society & Wellcome Trust Sir Henry Dale research fellow with over 15 years’ experience working with S. pyogenes. She has also recently been awarded a HEFCE ODA Quality-Related research grant through the University of Sheffield with Dr de Silva and MRC unit The Gambia to study S. pyogenes in The Gambia. In her spare time, Claire enjoys long walks through streptococcal genomes and the peak district, knitting and attending pottery classes. She is a Gryffindor.

Alex Remmington

“My research implements aspect of genomics, molecular techniques and protein assays to investigate the role that bacteriophage play in the infectious processes associated with GAS disease. Bacteriophage can carry virulence genes between GAS, and Changes in their prophage complement have linked to upsurges of disease. As in the United Kingdom, we endure our fifth consecutive season of dramatically elevated rates of scarlet fever and invasive GAS disease, understanding the mechanisms by which these virulence factors are acquired, regulated and expressed could provide valuable insight into the coordinated molecular events that occur during pathogenesis.”

Alex is also Microbiology Champion for the Microbiology Society, and he is passionate about equality and diversity in science, feminism, and infectious disease research. He loves dogs, Stevie Nicks and true crime novels. He hates collecting things from stores, early mornings and Snapchat.

Callum Mynett

“My research interests lie in elucidating the role of certain protein components of biofilm in GAS. Deaths resulting from severe recurrent infections contribute significantly to the global disease burden, and biofilm formation is likely contribute to this recurrence. By combining molecular biological and biophysical techniques with state-of-the-art structural biology and imaging technologies, I aim to assess the contribution of specific proteins in biofilm formation, thus informing novel treatment of GAS infections.”

Callum’s research is funded by the Rosetrees Trust, the Florey Institute and Imagine and is Co-supervised by Dr. Rosie Staniforth. He enjoys raclette parties, jazz music and jaunts to the French Riviera. He dislikes mornings and tonic water.

Join the Turner Laboratory!

The Turner laboratory is currently recruiting a research technician based here at the University of Sheffield. If you are interested in joining the team, click here to find out more.

Previous Students

Jennifer White – BSc Project Student 2017-2018
‘Investigating emm type diversity among non-invasive clinical isolates of Streptococcus pyogenes recovered from skin and throat specimens’
Rhiannon Newman – BSc Project Student 2017-2018
‘Investigating emm type diversity in recurrent and persistent Streptococcus pyogenes infections using non-invasive clinical isolates recovered from skin and throat specimens’
Ken Fong Chen – MSc Project Student 2017-2018
‘Phenotypic heterogeneity among strains of Streptococcus pyogenes isolated from clinical specimens during a local outbreak of invasive disease attributed to an uncommon emm type’

Day 7 – Investigating susceptibility of HIV patients to pneumococcal disease

15/3/2018

Understanding why HIV infection leads to increased risk of pneumococcal disease

People living with HIV who are on treatment remain at much greater risk of pneumococcal disease. The reasons for this are unclear and progress in this area would greatly impact people living with HIV.

This study finds that, despite antiretroviral therapy to treat HIV, there is a persistent low-level of virus in the lung; because of this the immune system of these patients is weakened which allows other infections to take hold, like pneumococcal disease.

Here the lead author, clinician and Florey scientist; Dr Paul Collini answers a few questions about this study.

Dr Collini explains,

“We wanted to understand why people living with HIV, who are on treatment, remain at much greater risk of bacterial infections in the lung. Usually, resident immune cells called macrophages remove bacteria and foreign particles. In healthy individuals, these lung-cleaning specialists would deal with these bacteria before they cause disease, yet these processes are lacking in people living with HIV.

We extracted macrophage cells from volunteers, with and without HIV, and tested how well they killed bacteria in the lab. We found these lung-cleaning macrophages had lost some of their ability to kill the bacteria and that a low-level of HIV virus and viral protein was in-part to blame.
This study suggests lung health needs special attention in people living with HIV. In particular; we need to develop new strategies to reduce bacterial infections in the lung which can lead to pneumonia. The work also suggests a common pathways exist that lead to susceptibility to bacterial infections in patients living with HIV and those with other types of lung-related health issues, such as: chronic obstructive pulmonary disease (COPD).

Further work to characterise lung health in people living with HIV in the future and identifying ways to ‘fix’ lung macrophages are the next challenges for this work”

Read the full article here

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Day 6 - Baking for Antibiotic Awareness Week

14/3/2018

The Florey students get their oven mitts out!

To mark the most recent Antibiotic Awareness Week, Florey students organised a bake sale in collaboration with the Sepsis awareness team from The Royal Hallamshire Hospital. The bacteria themed cakes 'proved' a great way to engage the public in conversation about sensible antibiotic use. Thanks to a great effort by all our Florey bakers we raised £42.18 for the Sheffield Teaching Hospital (@SheffieldHosp).

The theme of this years' event is "Think twice, seek advice" reminding people to never take antibiotics without first consulting a qualified healthcare professional. During the winter months, when everyone is full of a Cold and wait times to see a GP are long, it can be more tempting than ever to take left over antibiotics. However, in the case of a Cold, taking antibiotics will have no effect on the virus causing the infection and may cause unwanted side effects. The best thing you can do is give yourself time to get plenty of rest and consult a doctor if your symptoms persist.

Follow the official British Science Week hashtag on Twitter at #BSW18

Day 5 – Molecular coordination of Staphylococcus aureus cell division

13/3/2018

Using the latest microscopy to rethink the model of bacterial growth and division

The cell wall is a structure surrounding bacteria and is essential for structural support, it is often a target for antibiotic treatment for this very reason.

The ‘building blocks’ of this cell wall is peptidoglycan, this is a long chain formed of sugars and amino acids that provides a structural role.

To create this incredibly important structure the cell has to coordinate the process. In S. aureus synthesis of this begins at the middle of the cell and is guided by dynamic cell wall synthesis machines.

An interesting finding of this paper is that not all peptidoglycan insertion occurs at the leading edge of the septum in this species, causing researchers to rethink the model in which they look at S. aureus cell division.

To read the full article and find out more about how the techniques which generated these images, follow this link

Follow the official hashtag on twitter at #BSW18

Day 4 – Bacterial growth processes can be shut down

12/3/2018

Research from the Florey Institute has found a new ‘off’ switch for bacterial growth.

Most infectious bacteria are surrounded by a strong cell wall that protects them from breakage. Penicillin, and similar antibiotics have been used to treat serious infections for decades by compromising the strength of the cell wall, killing the bacteria and hopefully saving the patient. Penicillin works by selectively ‘shutting down’ a critical component in a large machine that is constantly building new cell wall as the bacteria grow.

Researchers set out to investigate how the cell wall building machinery is controlled in the bacterium Streptococcus pneumoniae, which causes serious infections like pneumonia, sepsis and meningitis. They used a DNA sequencing technique to search for new genes involved in the cell wall construction pathways. Through this work they identified MacP; a new protein component that is required for cell wall construction – effectively acting as an ‘on/off switch’.

This finding links cell wall growth to many other developmental processes within the cell and further work will help us to understand how the MacP-switch operates and, ultimately, what signals trigger the function of the cell wall building machines.

Dr Fenton, who led the study in Sheffield, explains:

“The last few years has seen a revolution in the way we think about cell wall growth in bacteria. Recent findings have redefined the biochemical activities of many factors we thought we understood. This paradigm shift has opened many exciting lines of investigation, including how the cell wall building machinery is regulated.”

“It is now clear that different types of bacteria approach the regulation of cell wall growth in different ways. This study breaks new ground in our understanding and links cell wall growth to central regulatory processes within the bacterial cell.”

“With bacteria pushing back against antibiotic treatment there is an ever-increasing burden on current clinical practices. Cell wall growth remains one of most widely used targets when treating bacterial infections. Therefore, there has never been a more urgent need for us to understand these processes.”

The full paper entitled: Phosphorylation-dependent activation of the cell wall synthase PBP2a in Streptococcus pneumoniae by MacP has been published recently in PNAS (Proceeding of the National Academy of Sciences). READ IT HERE.

For more British Science week stories, follow the official hashtag on twitter at #BSW18

Day 3 – Using zebrafish to study how infections enter the brain

11/3/2018

Meningitis and translucent bodies

Dr Simon Johnston @JohnstonLab explains his labs interest in the brain and meningitis.

"The brain is the most complex tissue in the human body and one of the least well understood.

The brain needs many different nutrients but must be protected from toxins and infection.

Infection of the brain, commonly in the form of meningitis, is difficult to treat and is most common in the most vulnerable patients.

We have found a new way to study how infections enter the brain and how we might prevent the damage they cause during meningitis.

We are using the zebraifsh to study human infections and meningitis. Zebrafish have translucent bodies that means we can study how infections enter the brain and how they cause damage.

We are now using this technique to find new treatments for meningitis."

Dr Johnston's lab published a manuscript last month looking how zebrafish can be used to study these processes.

For more information see paper LINKED HERE.
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Day 2 – Microbe Safari Public Outreach Event

10/3/2018

Throwback to learning about how clean your hands are and a giant inflatable E. coli!

As part of the Florey Institute launch celebrations (#TDDW), our scientists took a ‘Microbe Safari’ to the Winter Garden in Sheffield City Centre. We hosted a range of activities, all overseen by the giant inflatable E. coli.

With lots of fun interactive activities on offer, it was the perfect opportunity for members of the public to learn more about bacteria, infectious disease and the work we do at the Florey Institute.

Activities included an opportunity to see how many bacteria grow on your hands. For the results of these experiments, please visit: ‘What's growing on YOUR hands’. There was also the chance to see how good your hand washing technique really is with the help of special UV dust!

To show the diversity, and beauty, of bacterial cultures, our scientists bought along agar plates containing lots of different types of bacteria. There was also the chance to learn about microscopes and see how we use different models to carry out our research. 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 from the Florey who volunteered their time to help out, and to everyone who visited our exhibits!

See #MicrobeSafari for more images of the event!

Day1 - British Science Week!

9/3/2018

It's British Science Week!

At the Florey Institute we will be celebrating this national event by posting and tweeting about all the exciting news, research and work going on at our Institutes.

Follow the official hashtag on twitter at: #BSW18