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Third year IITM student, Layal Liverpool, has been awarded a prestigious BSA media fellowship, funded by the Society for Applied Microbiology. The fellowship will allow Layal to spend 2-6 weeks this summer working at a large media outlet to develop skills in science communication and journalism.
BSA Media Fellows are mentored by professional journalists and learn how the media operates and reports on science, how to communicate with the media and to engage the wider public with science through the media. Layal is yet to find out which media outlet will host her placement, however previous Fellows have worked in major organisations such as the BBC, The Guardian and Nature News.
Following their media placement, Fellows attend the British Science Festival in September, where they have the opportunity to gain valuable experience working in the BSA Press Centre alongside a range of media organisations from all over the UK.
In response to being awarded the fellowship, Layal said “I am absolutely delighted and extremely grateful for this fantastic opportunity!”.
The application process for the fellowship is extremely competitive and the IITM Programme is very proud of Layal for being selected. We hope she finds the experience fulfilling in shaping the direction of her scientific career.
Congratulations to Dr. Jack Dorling who recently passed his DPhil Viva exam!
Jack undertook his project in Prof. Petros Ligoxygakis‘ lab in the Department of Biochemistry. His interests in host-microbe interactions took him to study peptidoglycan metabolism and interactions with the host innate immune system at the cell surface of Staphylococcus aureus for his project.
Good luck Jack with your future career!
Congratulations to IITM student, Laura Makin, who recently passed her DPhil viva!
Laura joined the IITM programme in 2013 and undertook rotation projects with Omer Dushek and Anton van der Merwe at the Dunn School and Jeanne Salje and Nick Day at MORU, Bangkok, Thailand before settling in Eva Gluenz‘s lab at the Dunn School for her main project.
Laura’s project looked at host-parasite interactions in Leishmania which causes the neglected tropical disease leishmaniasis. In particular, Laura focussed on the subcellular origin of extracellular vesicles in Leishmania and their effects on host macrophages.
Congratulations again to Laura and good luck for your future career.
Congratulations to Florian Brod who completed a viva exam and successfully defended his DPhil thesis today.
Florian has spent the past three years at the Jenner Institute working with Professor Sumi Biswas and Professor Adrian Hill. His DPhil project focussed on developing multi-stage vaccines against malaria. Florian designed a virus like particle to induce immunity against infection in humans and to block transmission via the mosquito vector. In addition to this he studied protein-protein interactions between the parasite and mosquito to identify further targets that could be exploited for a transmission blocking vaccine.
In his first year, Florian undertook rotations at the Mahidol-Oxford Research Unit, Bangkok, Thailand with Professors Susie Dunachie and Nick Day and at the Dunn School with Professor Quentin Sattentau as well as at the Jenner Institute.
We wish Florian all the best with his future career.
By Felix Richter and Sarah Wideman
Research needs to be communicated and discussed, whether in big conferences or in a smaller format, such as a research symposium. The IITM programme holds an annual research symposium which provides a great platform for students to improve their presentation skills and to receive feedback on their project from course mates, supervisors and professors. In addition, the day provides opportunities to network, get career advice and socialise in an informal setting.
After a quick cup of coffee and biscuits, the fourth-year students were first up to present. With just one year to go until their thesis submission, all projects had interesting and novel findings, but left time to address some final unanswered questions. Topics presented ranged from iminosugars for antiviral defence (Beatrice Tyrrell) to virus RNA structure (Bernadeta Dadonaite) and CRISPR-based immunological screening methods (Corinna Kulicke). We are already looking forward to seeing the final data from these projects and hope to share more information about the projects as soon as they are published.
After a small break, it was the third-years’ turn. One year into their research projects, the amount and quality of the presented research data was impressive. The topics were diverse and included infection projects such as bacterial toxin-antitoxin systems (Hannah Berens), immune cell chemotaxis during HIV infection (Cherrelle Dacon), microbial bioinformatics of Neisseria species (Marianne Clemence) and viral zRNA sensing (Layal Liverpool), as well as more immunological projects about T-cell transcriptomics (Lucy Garner) and the immunological response to malaria (Richard Morter). The presentations engaged both students and researchers in rewarding discussions and the input was seemingly gratefully welcomed by the presenters.
After a combined lunch break and poster session, a familiar face returned to her old alma mater. Dr. Meike Assmann graduated in 2016 from the IITM programme and has left academia to pursue her passion for consultancy, working with Alcimed. She described her path from the lab to her current job as a project developer for clients in the health care industry. She also talked about how we can apply the skills we develop during a PhD to succeed in a career outside the lab. This inspiring talk highlighted the many ways that a DPhil degree from the IITM programme can take you.
The student presentations were concluded by the second-year students. This cohort recently begun their DPhil projects, so the data was still preliminary, but the ideas big and convincing. Once more the variety of topics was one of the highlights of this session. The topics ranged from characterisation of HIV-related genes (Alun Vaughan-Jackson), autophagy in the bone marrow environment (Felix Richter) and T cell signalling (Johannes Pettmann) to antiviral iminosugar therapy (Juliane Brun) and malaria vaccine development (Robert Ragotte). We look forward to seeing more of their results at the IITM symposium 2018 and we all wish them the best of luck for their new projects.
The symposium concluded with this year’s keynote speaker, the first to be invited from outside the UK; Professor Henrique Veiga-Fernandes from the University of Lisbon. He leads research on the S(c)ensory Immune System Theory, describing the potential role of other cell types to govern the behaviour of immune cells in multicellular organisms (1). His presentation captivated the entire room with insights into how communication between the nervous system and the immune system is important in maintaining immune homeostasis, focussing on two recently published papers which discuss the role of neuroregulatory factors in affecting the function of innate lymphoid cells (2, 3).
For the symposium’s grand finale, there was a drinks reception and formal dinner in the Old Dining Hall at St Edmund Hall. Both the students and faculty greatly enjoyed this opportunity to socialise and to continue the day’s scientific discussions. Here, the programme also officially thanked and said farewell to Professor Fiona Powrie. Fiona was one of the founders of the programme and has recently stepped down from her position as programme director. We again express our gratitude to Professor Powrie for her contribution to the programme over the years. Without her hard work, none of the programme’s achievements to date would have been possible.
We are all already looking forward to a new year of science and to see how our work has progressed at the IITM symposium 2018.
- Veiga-Fernandes H, Freitas AA. The S(c)ensory Immune System Theory. Trends Immunol. 2017;38(10):777-88.
- Cardoso V, Chesne J, Ribeiro H, Garcia-Cassani B, Carvalho T, Bouchery T, et al. Neuronal regulation of type 2 innate lymphoid cells via neuromedin U. Nature. 2017;549(7671):277-81.
- Ibiza S, Garcia-Cassani B, Ribeiro H, Carvalho T, Almeida L, Marques R, et al. Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence. Nature. 2016;535(7612):440-3.
Congratulations to Dr. Ben Nilsson who successfully defended his thesis yesterday (December 4th 2017).
Ben has spent the past 3 years working on the influenza A virus RNA polymerase in Ervin Fodor‘s lab at the Dunn School, University of Oxford.
You can read more about what Ben got up to during his project in a post he wrote earlier this year summarising the paper published on his work.
The Programme wishes Ben all the very best with his future career.
Welcome to the latest cohort of IITM students! Find out more about them and their interests here.
Last month (October 2017) we welcomed five new students to the IITM DPhil programme: Robert Friedrich-Donat, Mari Johnson, Lea Nussbaum, Hannah Sharpe and Sarah Wideman.
Robert studied Immunology at the University of Edinburgh and is now working in Simon Draper‘s lab investigating red blood cell invasion by the malaria parasite. Mari is also focusing on malaria during her first rotation, designing epitopes for a potential vaccine in Matt Higgins‘ lab. Before coming to Oxford, Mari studied Cellular and Molecular Medicine at the University of Bristol. Lea studied Molecular Biotechnology at Heidelberg University in Germany. She is currently working in William James‘ lab, examining cellular interactions during HIV infection. Hannah studied Biology and Immunology here at Oxford and is now working in Ellie Barnes‘ lab characterising immune responses to hepatitis C vaccination. Sarah studied Biomedicine at the Karolinska Institute in Sweden. She is now undertaking a rotation in Hal Drakesmith‘s lab looking at the effect of iron deficiency on immune function.
Author: Layal Liverpool
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Rob Ragotte describes his experiences on rotation in Ho Chi Minh City, Vietnam.
When I accepted my place in the IITM programme in February 2016, I prepared myself for what I thought would be an interesting, illuminating, exciting, challenging, stressful, and sometimes demoralising few years. What I did not prepare for was wandering around a grocery store for an hour unable to identify a single food I could confidently cook. I did not imagine myself cruising through the streets of Ho Chi Minh City on the back of a motorcycle. And it never crossed my mind that the words cảm ơn (thanks) and không đường (no sugar) would be essential additions to my vocabulary.
As part of the IITM programme, all first year students undertake three lab rotations. For many, this will allow them to get comfortable in three different labs around Oxford where they will learn new techniques and refine their research interests.
However, students are also able, and encouraged, to explore labs at one of Oxford’s major overseas programmes. This allows students to travel to Bangkok, Thailand; Ho Chi Minh City, Vietnam; or Kilifi, Kenya, to work at the Oxford/Wellcome Trust centres situated in those cities.
For my third rotation, I opted to go to Ho Chi Minh City, to work under the supervision of Prof. Stephen Baker at the Oxford University Clinical Research Unit (OUCRU). The goal of my project was to understand the genetic factors that enable Klebsiella pneumoniae, a common and normally harmless bacteria, to cause disease in otherwise healthy individuals. K. pneumoniae can sometimes cause life-threatening infections if it enters the bloodstream or brain.
For the project, I analysed the all the genes contained in 83 suspected K. pneumoniae samples isolated from patients with infection of the blood. Although I had limited experience doing complex computational analyses before, I quickly found myself mastering a host of new skills needed to carry out my project.
I found an abundance of genes transferred from other disease-causing bacteria, as well as genes that confer resistance to a range of antibiotics in the blood isolates. This might help to explain why K. pneumoniae sometimes causes disease and sometimes does not.
While working on this project, it was not immediately clear to me why I needed to be in Vietnam. After all, most of what I did was computer based and much of my day-to-day supervision was via email. My physical presence in Vietnam seemed unnecessary. I could just as easily do my work from Cardiff or Calgary. So I thought.
As my project progressed, I realised not only was it beneficial to be in Vietnam, it was absolutely essential. By living in Vietnam, albeit briefly, I began to understand some of the unique challenges faced by clinicians and scientists alike. The realities of clinical care in a middle-income country profoundly impact not only the type of research that is conducted, but also the how we think about and implement potential solutions. It is not enough to merely identify a problem from afar. Though antimicrobial resistance is particularly problematic in Vietnam, it is not localised to single region, country or continent. It is a global problem and requires global partnerships, coupled with a mutual understanding of the specific goals and challenges, if it is to be solved. My immersive experience emphasised and contextualised the importance of conducting research on a major global health problem.
I do not mean to suggest that I now understand the intricacies of the Vietnamese health care system, or the particular nuances of operating in a middle-income country. I know very little. However, some of the unknown unknowns have now become known unknowns, which is a substantial improvement. Recognising that there are fundamental differences between conducting health research and providing clinical care in a middle-income setting will ensure conversations about global health interventions evolve from paternalistic to empowering. It will allow us to move from a prescriptive approach to one where local idiosyncrasies are considered.
My time in Vietnam was not as orderly as I initially envisioned. Certainly there were challenges and it was, at times, tumultuous. Though, I was fortunate to have an excellent supervisor and resourceful colleagues that ensured I was both productive in my work, and enjoyed my Vietnamese experience. I fly back to the UK grateful for the opportunity and optimistic about the next three years.
Author: Rob Ragotte
Rob is an IITM student entering his second year of the programme.
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Richard Morter explains the findings of a recent study he was involved in during his rotation project at the KEMRI-Wellcome Trust Research Programme in Kenya.
Malaria is a mosquito-transmitted parasitic infection and although it is treatable if diagnosed early enough, approximately half a million people die each year from malaria. Around 70% of these deaths are in children under the age of five.
Malaria therefore presents a huge burden to global health. Although incidence is reducing globally, there is still a long way to go to reach elimination. The most effective tools currently used to control the spread of malaria are the insecticide-treated bed nets and indoor residual spraying (the application of insecticides to the walls of people’s homes where mosquitos might rest).
Traditionally, malaria control programmes have involved blanket coverage of endemic areas, where every single house in an area is given bed nets or has their houses sprayed. However there is growing interest in adopting more targeted approaches where only those most at-risk are selected for intervention.
The advantage of this is largely economic. The hope would be that targeted intervention in a defined geographic area would yield the same overall reduction in malaria transmission as blanket coverage, but using fewer resources. This would mean more areas could be covered for the same cost leading to a more universal reduction in malaria transmission.
Malaria transmission intensity is inherently uneven across different areas. It’s unevenly spread across the tropical world with sub-Saharan Africa accounting for over 90% of all cases. It’s unevenly spread within Africa too. This unevenness is called spatial heterogeneity of transmission intensity.
In fact; as we zoom in on smaller geographic areas, we continue to see spatial heterogeneity. We can even see it right down at the single homestead level – infected children are not uniformly spread across a village but instead are tightly clustered together, living in either the same or adjacent homesteads. These locations are described as ‘hotspots’ of malaria transmission and could be targeted for control interventions.
Hotspots have been identified by our group in nearby villages along the Kenyan coast, Junju, Ngerenya and Ganze. Junju has moderately high transmission intensity whereas Ngerenya and Ganze have very low transmission intensity.
For targeted interventions to work, hotspots need to be detected accurately. In this paper, we investigated just how accurate current methods are in detecting hotspots.
The first question to ask is; do hotspots remain stable over time? In other words, if we use a previous year’s hotspot data, and direct control interventions to those locations, will the hotspots be in the same place the next year or are we chasing a moving target? In this study, we discovered that the hotspots are indeed stable over time in the high-transmission village, however there appears to be less stability in the lower-transmission villages. What may be required in the future is a more real-time approach where hotspots are detected as they form and immediately targeted.
The second question we addressed is; what method should be used to detect hotspots? We used three different methods to detect parasite infection and subsequently identify hotspots; microscopy, rapid diagnostic testing (RDT) and qPCR.
The gold standard method for malaria diagnosis is microscopy. It’s cheap and already almost universally available in malaria endemic areas, however it lacks sensitivity meaning infections with low numbers of parasites are often not detected.
RDTs work in a similar way to pregnancy tests and a band appears on the test stick if the blood sample contains parasites. They are also relatively cheap and might have slightly better sensitivity to microscopy.
A much newer and more sensitive tool is qPCR where parasite DNA in a blood sample is amplified in an enzymatic reaction. This amplification is detected and indicates a positive sample. qPCR can detect positive samples with much lower parasite counts than microscopy or RDTs, however it’s expensive and requires more specialist equipment.
We compared the abilities of microscopy, RDTs and qPCR to detect hotspots in settings of different transmission intensities and assessed the degree of overlap between hotspots detected by the methods. We found that hotspots were easily detected by all methods in the high transmission setting but microscopy was less reliable in the low transmission setting. The degree of overlap was least for RDTs. Microscopy also became more inconsistent and the hotspots it was detecting overlapped less with qPCR in the low transmission setting.
This is because RDTs and microscopy are less sensitive methods so are less reliable in being able to accurately detect hotspots especially when there are fewer positive samples. Because of this, we suggest that qPCR should preferentially be used particularly as transmission intensity decreases.
Overall, targeted malaria control programmes are an important part of elimination campaigns. Hotspots become more apparent as transmission intensity falls and becomes patchier, therefore hotspot targeting will become even more important in the future as global malaria incidence gradually declines. We found that qPCR becomes more important in this situation. More needs to be done to increase the accessibility of qPCR in malaria-endemic low and middle income countries by reducing cost and simplifying technologies.
Together, these strategies may help contribute to controlling and eventually eliminating malaria worldwide.
The full paper can be accessed at: https://doi.org/10.1093/infdis/jix321
Polycarp Mogeni, Thomas N. Williams, Irene Omedo, Domtila Kimani, Joyce M. Ngoi, Jedida Mwacharo, Richard Morter, Christopher Nyundo, Juliana Wambua, George Nyangweso, Melissa Kapulu, Gregory Fegan, Philip Bejon; Detecting Malaria Hotspots: a comparison between RDT, Microscopy and Polymerase Chain Reaction. J Infect Dis 2017 jix321. doi: 10.1093/infdis/jix321
Author: Richard Morter
Richard is now undertaking a collaborative DPhil project between the Jenner Institute, University of Oxford and the KEMRI-Wellcome Trust Research Programme, supervised by Professors Adrian Hill and Philip Bejon. He is characterising the Regulatory T cell response in a human malaria challenge model and looking at the consequences of malaria-induced Regulatory T cells on effective vaccination against malaria.
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Every IITM student writes a review shortly after starting their PhD project. Often this is about the literature directly relevant to their thesis. In my case it was different; a very good recent review about the background to my thesis already existed. Instead I decided to have a look at how the toxins I study could be transformed into medicine.
Bacteriocins, the toxins I study, are not toxic to humans but instead very specifically kill certain species or strains of bacteria. The bacteriocin most of my work focuses on, for example, is produced by a bacterium called Pseudomonas aeruginosa to kill other strains of the same species; its cousins, if you wish. This way they can defend or conquer ecological niches. Can we exploit these bacteriocins as antibiotics to treat bacterial diseases in humans?
Searching for evidence
Last summer I set out to find all the reports of people who had tried these bacteriocins to cure infections in animals. I found eleven such reports and two additional ones which just looked at the effect of bacteriocins in healthy animals. Finding these reports was the most difficult part of all. Most reports I read turned out to be irrelevant. One I had to request from the libraries’ archives. It was so old it only existed on paper, as compared to most scientific reports which can now be found online. I went up to the top floor of the Bodleian library in Oxford where I received an old linen-bound book.
Of the eleven studies I found, only six, all from this century, had actually identified the exact bacteriocin they worked with. Previously researchers had realized they were working with something toxic but were not yet able to identify it.
Next I analysed the data I had found. It looked very promising. In all cases the bacteriocins were able to resolve or reduce bacterial infections – something that keeps me motivated on days when my research is not that easy!
Better than traditional antibiotics?
One question you might have asked yourself is, but why do we even need new antibiotics? Don’t we already have many? We have 26 but our frequent (over)use during the last century has led to many bacteria developing resistance. In the past few years more and more cases of bacteria resistant to all antibiotics occurred. Meanwhile the development of traditional antibiotics has stalled since the last major discovery of a new drug back in 1987. Scientists are now turning to an array of alternative antibiotics to plug the growing gap. One very promising type are narrow-spectrum antibiotics, such as bacteriocins.
Bacteriocins only kill one species of bacteria or even a subset of that species. This is in contrast to traditional antibiotics which kill a wide range of bacteria. I like to think about it like this: Something as different from you as a tree, causes a disease. Nonetheless you are wiped out with it because you happen to belong to the same kingdom of life as the tree. This is exactly how broad the spectrum of traditional antibiotics is. Bacteriocins however have such a narrow spectrum they can differentiate between you and your cousin (figuratively speaking).
The disadvantage following from that is that one needs to identify the species and maybe even strain of bacteria causing an infection before starting the treatment. The huge advantage is however that only those bacteria that cause the infection are treated. Because traditional antibiotics kill all types of bacteria they also select for resistant mutants in all types of bacteria. With narrow spectrum antibiotics only one species out of the millions we carry in our body is put under selective pressure. (Selective pressure kills most but encourages the spread of resistant survivors). This way, narrow spectrum antibiotics, such as bacteriocins, do not promote antibiotic resistance.
The broad killing spectrum of traditional antibiotics also means that the delicate balance of health-related “friendly” bacteria in our body gets disturbed. Especially in elderly and weak people this can have devastating, even lethal effects, such as promoting C. difficile infections. The beauty of narrow spectrum antibiotics is once again that they leave all bacteria that are not related to the infection unaffected.
These aspects and some others which will determine the success of bacteriocins as antibiotics I have discussed in the second part of my review article. Especially helpful for this part was my Co-author Dr. Anne Six from Glasgow. Together we polished the article until we decided it was ready to submit. After incorporating some advice from the reviewers our review has finally been published. You can now read it here.
Author: Hannah Behrens
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Behrens, H.M., Six, A., Walker, D. and Kleanthous, C. (2017) The therapeutic potential of bacteriocins as protein antibiotics. Emerging Topics in Life Sciences. 1(1) 65-74