Experimental approaches for studying bacteria have changed dramatically over the last 20 years.  Among the most influential shifts in technology has been the increasing use of large sequencing datasets in research practice, which have allowed scientist to discover complex patterns of bacterial behaviour and reach a deeper understanding of the bacterial cell. This rapid advancement has many conceptual benefits but also comes at a significant cost, as laboratories struggle to integrate modern bioinformatics approaches with traditional microbiological research practice. But Don’t Panic. In our review article, we discuss these issues in a broad sense providing an introducing into next-generation sequencing methods for non-specialists whilst at the same time helping data-specialists understand how ‘wet’ scientists might view experimental proofs.

​In a joint interdisciplinary effort, researchers from the Florey Institute for Host-Pathogen Interactions at the University of Sheffield and the ​Milner Centre for Evolution at the University of Bath have now addressed this emerging schism in their latest review. 

​Prof. Samuel Sheppard, Professor and Director for Bioinformatics at the University of Bath said:
‘Population-wide genomic screens have revealed astounding genetic variation in bacteria. We must use this new information to learn more but we cannot ignore the scientific rigour of established molecular microbiology. With this article, we aim to provide a framework for integrating techniques for next generation microbiology.’
​

​The article ‘Next-generation microbiology: from comparative genomics to gene function’ has recently been published in Genome Biology. Read the full article here.
​
This work was supported by grants from the Medical Research Council awarded to Prof. Samuel Sheppard and Dr Andrew Fenton.

I am a third year PhD student at the School of Clinical Dentistry at the University of Sheffield. My interest in research budded from an MSc I had undertaken after completing my dental surgery degree.
​
Research on how materials interact with the oral environment led to an interest in how oral microorganisms interact with our body, in our mouths and beyond. This interest steered my move to the University of Sheffield in 2017 and my current PhD project. Under the supervision of Prof. Craig Murdoch and Prof. Graham Stafford, my PhD aims to study the role of oral microorganisms, particularly gum disease bacteria in the initiation of cardiovascular disease.
​

​The association between gum disease and heart disease is nowadays widely accepted by both the scientific and clinical community. None the less, there are several debates on how gum disease can affect blood vessels and the heart when bacteria and their secretions make their way from our mouths to our circulatory system. Through my PhD, I am researching the effects of periodontal pathogen infection on endothelial (blood vessel) cells, as well as the effects of systemic infection in zebrafish embryos. Changes in the cells and in the zebrafish’s health allow us to understand more the mechanisms that might drive this association.

​I’m Jaime, a third year PhD student. I work in Johnston lab of Bateson Centre of the University of Sheffield. My project focusses on how immune cells eat up particles, an important cellular process to control infection called phagocytosis. We greatly rely on imaging methods and simulations to understand the mechanical underpinnings of this process, and scanning electron microscopy is one of our very important tools (see images below). It does not only provide very good resolution of cells being examined, but also allows one to visualise changes on the surface of immune cells when dealing with different types of particles and microbes.
​

​It is important to understand phagocytosis because it describes one of the fundamental means of destroying foreign particles, usually infectious ones called pathogens, by our immune system. This normally requires an immune cell to wrap its membrane around its target so it can be internalised and killed. Phagocytosis is not an exclusive property of our innate immune cells, but also seen in single-celled organisms such as amoeba. We have recently identified a common membrane feature in these cells, and currently investigating its role in the phagocytic uptake and other cell functions. Findings in this project would hopefully give us a better understanding of the mechanics of engulfment process, especially in taking up different types of pathogen in the midst of emerging infectious diseases and rapidly changing environment.
​

Hi, I am Ernesto and I am happy to share my experience as a PhD student at the University of Sheffield. I came to Sheffield almost four years ago from Mexico and now I am at my final year of the PhD.

​I am doing my research in post-translational modifications in the bacterium Neisseria gonorrhoeae to discern how it affects the metabolism and pathogenesis. I have the fortune to work in the Infection, Immunity and Cardiovascular Disease department which is located within the Royal Hallamshire Hospital. I would say that the advantage of being at this building is that you could be growing bacteria and at the same time having an incredible view of Sheffield. 

One of my passions and guilty pleasures of being a scientist is imaging. This image (above), is the infection of macrophages with N. gonorrhoeae and it was the first time that I observed this process in real time. Showing that a mutant of the gonococcus is easier to phagocytose.
​
I hope that with these results my lab continue to study acetylation since it seems a good candidate for a therapy against gonorrhoea.

I’m Megan Cavanagh and I am a 2nd year PhD student in the PRIME Global Health group based in the Medical School at The University of Sheffield. My project involves studying the interaction between vaginal microorganisms and preterm birth. Our lab is investigating biomarkers of preterm birth and why some pregnant women with infection give birth too early (before 37 weeks) but some do not.

Organisms like Group B Streptococcus are thought to contribute to the premature rupture of the foetal membranes (this is the term for when “waters have broken”). One part of my project is a collaboration with Chris Holland, head of the Natural Materials group. We are testing the physical properties of the foetal membranes with and without exposure to infection to see if these organisms can alter the tissue.
​

​Antibiotic resistance is on the rise and is projected to kill over 10 million people per year by 2050. Therefore the need to find a successor to antibiotics has become urgent.

I have always been interested by the interaction of light with matter. Appropriately, my chosen PhD project is Antimicrobial Photodynamic Therapy (PDT). PDT is the use of a light activated molecule to cure a disease. Using unconventional synthetic techniques I have managed to synthesis a novel antimicrobial PDT agent based on a metal complex. I've used this chemical to kill infectous bacteria called P.gingivalis and MRSA, reducing their numbers by 3 orders of magnitude even at a very low concentration of 5 nM. Furthermore, this complex is able to target bacteria internalised in human cells, which conventional antibiotics are unable to do. I look forward to finishing this work and seeing what these compounds can do to help patients in the future.

Isuru Muthukdaarachchi outside the Royal Society of Chemistry
​

​I originally moved to the UK from Sri Lanka in 2011 to pursue a degree in Chemistry. In Sri Lanka a prominent place is given to medicine and engineering while research subjects such as chemistry and physics are not heavily practiced. So I was in awe of the resources British universities poured into scientific research.
​
​I feel very privileged to have access to virtually limitless equipment and chemicals on demand in order to carry out my research to its full potential. Upon completion of my PhD I intend to continue working on antimicrobial PDT, using every resource at my disposal, expanding into antiviral PDT with special focus on dengue fever, which affects a large population of Sri Lankans yearly. I will also focus greatly on combining photochemical and biomimetic techniques to synthesise novel fuels in order to store energy harvested from the sun to combat global warming and help make the world green once more.
​

My name is Mahrukh Shameem and I am first year PhD student in the department of Infection, Immunity and Cardiovascular Disease. My project is supervised by Dr Simon Johnston based in Firth Court.

Using genetic studies, different genes and proteins that have been linked to respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma. From these studies they found that a protein was showing up highly: interleukin 33 (IL-33). This molecule has been linked to disease severity and is being researched as a target in treatment for respiratory diseases. But little is known about IL-33. Thus, my project - in collaboration with AstraZeneca use mice models to observe how this pathway affects our immune system so that we may exploit it for therapeutic potential. We aim to understand the effects of IL-33 in lung disease, as a therapeutic target for chronic lung disease therapy.

​Currently I have a lot of training to complete at the start of my PhD. This involves training on new equipment such as the microscopes and mice training. I also have a lot of background reading that I am currently doing so that I can understand what we know about my field and plan future work. My favourite part of my PhD has been learning new techniques and the mice work, but this also the most challenging part. Not having done these techniques before is difficult but going into lab with a challenge is very exciting! I have the chance to learn new things from other researchers, which helps me communicate better and learn new skills.

​I’m Rebecca, a second year PhD student part of the medical research foundation national training programme in antimicrobial resistance. I am a member of the Condliffe group, looking at the interaction of bacteria with immune products in low oxygen conditions.
 
While bacteria are establishing an infection within the human body, they are fighting against multiple pressures. The bacteria are exposed to low oxygen conditions and a multitude of immune products found at sites of infections. I am looking to see if these conditions are driving the evolution of bacteria and if being in these conditions is linked to characteristics of challenging infections found in the clinic. I will assess this by evolving bacteria and then looking for genetic changes through whole genome sequencing. I will also compare how the bacteria are killed by immune cells and antibiotics.
 
I am currently carrying out an evolution experiment, growing the bacteria in stresses found in the human body. In the next few months I should be able to see if the bacteria are able to overcome the stresses I am exposing them to.
​

​S. pneumoniae causes many life-threatening diseases, including sepsis, meningitis and pneumonia. Therefore this bacterium a major cause of death worldwide, with highest infection rates among infants, elderly people and immunocompromised individuals. S. pneumoniae infections are commonly treated with beta-lactam antibiotics like penicillin, yet an alarmingly high number of isolates from patients has developed resistance against this type of antibiotic, leaving patients at risk. While the introduction of pneumococcal conjugate vaccines led to a reduction of infections there continuously new antibiotic resistant strains emerging that are not covered by the vaccination program.
​

​To counteract the global threat of antibiotic resistance, it is important to understand the biological mechanisms underpinning resistance in S. pneumoniae. This is why my project aims to identify and characterise novel genes linked to antibiotic resistance. To this end, we performed a large-scale genetic screen in the presence and absence of penicillin. This approach will point out which genes are essential under antibiotic selection, and likely involved in penicillin resistance mechanisms.
 
So far, I have focused on building the large-scale ‘libraries’ of bacterial cells we need for the genetic screen. As you can tell from the pictures, I needed loads of agar plates to accommodate all the bacterial cells and had to rely on everyone in the lab to help me harvest the cells and prepare them for sequencing.
 
I am currently waiting for the results of the screen and I am very excited to find out about which genes could play a role in penicillin resistance, so we can further investigate them. 
​

​Hello! We are Kirsty Bradley and Jo Mckenzie and we are 2nd year PhD students supervised by Prof. Alison Condliffe, Prof. Ian Sabroe, and Dr Lisa Parker.
​
We both work in the academic unit of respiratory medicine investigating the responses of respiratory viruses (rhinovirus and respiratory syncytial virus).These viruses are associated with the common cold, however certain individuals are more susceptible to these infections (young children or those with asthma) whereby symptoms may become more severe and in some cases fatal.

To investigate viral responses in the lungs during infection, we grow airway cells in our lab that have been isolated from donors. This is a complex experiment to manage and therefore much of the 1st years of our PhDs involved optimising our methods and liaising with other members of the department, specialists based at other universities and the company who provided the cells.

Our experiments involve infecting the airway cells with virus. Over the course of the week we then collect samples for analysis using a range of techniques including Western blotting, ELISA, qPCR, and immunofluorescence.
​
Using our approach, we’re hoping to contribute to the wider field of research concerning respiratory viruses with the potential of developing therapeutics.