Food BioSystems DTP Gut bacteria and their DNA as elicitors of host beneficial responses

Probiotics have been proposed as a natural therapy against inflammatory bowel disease (IBD) because of their ability to reset microbial balance and restore appropriate immune responses. However, the oral administration of probiotics may exacerbate gut inflammation due to the fact that, as many other microbes, they are recognised by immune cells such as macrophages in an extracellular manner. Fortunately, our group has recently discovered that some probiotic bacteria are only sensed by macrophages once they have been phagocytosed, resulting in the production of molecules that alleviate inflammation. In this study we will determine the mechanisms that our probiotic bacteria utilize to interact with macrophages and whether their DNA is the main driver for the activation of protective responses following phagocytosis. We will also monitor markers associated with inflammatory exacerbation and/or mitigation in human macrophages exposed to our bacteria to evaluate their feasibility as a potential probiotic therapy against IBD.

Start date
1 October 2019
Duration
4 years
Application deadline
Funding information

This project is part of the FoodBioSystems BBSRC Doctoral Training Partnership (DTP), it will be funded subject to a competition to identify the strongest applicants. Due to restrictions on the funding, this studentship is only open to UK students and EU students who have lived in the UK for the past three years.

The FoodBioSystems DTP is a collaboration between the University of Reading, Cranfield University, Queen’s University Belfast, Aberystwyth University, Surrey University and Brunel University London. Our vision is to develop the next generation of highly skilled UK Agri-Food bioscientists with expertise spanning the entire food value chain. We have over 60 Associate and Affiliate partners. To find out more about us and the training programme we offer all our postgraduate researchers please visit https://research.reading.ac.uk/foodbiosystems/

About

The incidence of gut inflammatory disorders such as such as the irritable bowel syndrome (IBS) is increasing globally, with devastating consequences in animal production and public health. These disorders are caused by gut microbiota alteration and a dysfunctional mucosal barrier that allows the penetration of large amounts of microbes into inner parts of the gut, where immune cells such as macrophages gather to cope with this microbial invasion. The macrophage response results in the production of pro-inflammatory cytokines such as TNF-a, a molecule that, before the onset of IBS, helps with infection clearance; but once the syndrome has developed, is completely adverse as it causes a perpetual cycle of inflammation due to the continuous recruitment of macrophages. In this respect, the use of probiotics that induce other cytokines such as type-I interferons (IFN-I) has been proposed as an alternative therapy against IBS. On the one hand, IFN-I inhibits the production of TNF-a in macrophages, thereby limiting inflammation. On the other hand, probiotics help reset the gut microbiota and restore appropriate immune responses. However, the oral administration of probiotics able to activate IFN-I has also resulted in the production of TNF-a due to the fact that, as any other bacteria, probiotics are extracellularly recognised by macrophages.

Here we present the exciting discovery that a particular probiotic bacterium -Lactobacillus plantarum- evades the extracellular response of macrophages. By contrast, we have observed that macrophages sense the intracellular presence of L. plantarum, resulting in IFN-I production at the expense of TNF-a. We also know that this L. plantarum possesses proteins on its surface that are important for macrophage adhesion, which facilitates internalization for the subsequent activation of IFN-I.

   Based on our preliminary observations, this study will address the following questions:

  1. Are the adhesion proteins what make L. plantarum so appealing for macrophage internalization?
  2. Are intracellular pathways such as DNA sensors the main drivers of IFN-I activation following the internalization of L. plantarum?
  3. Would L. plantarum trigger a protective immune response against PI-IBS in the long term?

The data resulting from the first two questions will help us understand the mechanisms that L. plantarum utilizes to activate IFN-I production. The identified mechanisms could be further exploited to trigger IFN-I-based protective responses as a tool to combat gut inflammatory disorders. The results generated from question 3 will be essential to expand the potential use of probiotics as a therapy against IBS in animals and humans.

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Apply for a FoodBioSystems PhD

Eligibility criteria

This project is suitable for students with a degree in biological sciences, microbiology, food science or a closely related science. The PhD student is expected to contribute intellectually to the development of the project to maximise the results obtained. This person will develop sound laboratory and scientific skill to become a well-trained molecular microbiologist with sound expertise in probiotics and gut immunology. Previous education in microbiology and innate immunology is desirable; and ideally having some experience in working with bacteria and/or immune cells.

This project is part of the FoodBioSystems BBSRC Doctoral Training Partnership (DTP); it will be funded subject to a competition to identify the strongest applicants.  The student will receive a full research-council studentship.

Due to restrictions on funding, this studentship is only open to UK students and EU students who have lived in the UK for the past three years.

Applicants should have fluent written and spoken English.

How to apply

If you are interested in applying for the Surrey-based FoodBioSystems DTP Studentship, you will need to submit two applications to be considered for funding under the FoodBioSystems BBSRC Doctoral Training Partnership (DTP) between the University of Surrey and the University of Reading.

Please follow the process below to help you prepare and submit your application.

Apply for a place on the PhD course

Two separate applications will need to be submitted:

Please make sure you indicate on your application to the University of Surrey that you are applying for the Surrey-based FoodBioSystems DTP Studentship scheme. You are also advised to ensure that you include your degree transcripts and references in the application – not providing these documents can slow the process down.

University of Reading Application:

Complete the Reading FoodBioSystems DTP PhD Application Form and email the application form to foodbiosystems@reading.ac.uk. More information can be found on the Reading website.

University of Surrey Application:

Students will also need to apply through the Surrey Veterinary Medicine and Science PhD course pages. Applicants do not need to prepare a separate research proposal, however, should submit their Reading application form in its place. Please make it clear on your application that you are applying for funding through the FoodBioSystem DTP.

Deadline: Your studentship application both at Surrey and Reading, must be submitted by 5:00pm GMT 6 March 2020.


Application deadline

Contact details

Jorge Gutierrez-Merino
20 AY 03
Telephone: +44 (0)1483 683751
E-mail: j.gutierrez@surrey.ac.uk

The selected PhD student will benefit from training in multidisciplinary skills, specialised for scientific research and transferable to food industry. This student will receive scientific and technical training in the area of molecular & cellular biology, advanced microscopy, high-throughput technologies and bioinformatics; as well as aiming to gain other transferable skills (e.g. project and personal management, scientific writing, supervision, ethics) and manage/supervise career progression, to ensure optimal employability. The PhD student will also have the opportunity to interact with post-doctoral researchers, MSc students and undergraduates in our laboratories, with access to state-of-the-art facilities including multi-mode fluorescent detection plate readers, microscopy, flow-cytometry and RNA/protein stations to carry out transcriptional analysis and immunoblotting.

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