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‘Bacteroides fragilis ubiquitin: Investigating the impact of this molecular mimic’

School of Biological Sciences | PHD

Applications are now CLOSED
Funding
Funded
Reference Number
SBIO-2020-1253
Application Deadline
29 February 2024
Start Date
1 October 2024

Overview

When a gut symbiotic bacterium weaponises a host protein to use in intraspecies competition what is the impact on the host? This project focuses on the gut anaerobe, B. fragilis. This bacterium is found in all humans, however, some of the strains produce a homologue of ubiquitin and recent research has shown that this is used by the encoding strains to limit the growth of competitors. Ubiquitin was, until recently, thought to be exclusive to eukaryotic cells and therefore host immune cell tolerant, however, autoantibodies to ubiquitin have been associated with immune-mediated inflammatory diseases. This research will examine if and how this bacterial homologue could be responsible for the breakdown in immune tolerance and contribute to the development of autoimmune disease.

Bacteroides fragilis is a resident member of the gut microbiota and an important promoter of human health. Some strains have been shown to secrete a ubiquitin homologue (termed BfUbb) and recent research has indicated that this protein is important for B. fragilis in intraspecies competition in the gut environment [1]. There is however limited research into the potential impact of this protein on the host [2]. BfUbb has 63% sequence identity, >80% sequence similarity and is >99% structurally similar to human ubiquitin (HUbb) and is considered a molecular mimic. Ubiquitin is central to function in all eukaryotic cells so exposure to a molecular mimic may break tolerance or activate preexisting but unreactive immune cells resulting in the production of autoantibodies. Autoantibodies attack endogenous structures as they are unable to distinguish between self and nonself material which results in a dysfunctional immune system and the development of autoimmune disease. There are over one hundred autoimmune diseases affecting 5% of the global population. The concept of molecular mimicry where microbial components share sequence and/or structural similarity is increasingly recognised as an influencing factor in the development of autoimmune diseases and is primarily due to the production of cross-reactive antibodies that are raised in response to shared immunogenic regions present on both microbial and host components. Autoantibodies to ubiquitin and changes in intestinal microbiota have been associated with the development and progression of various inflammatory diseases. The complex nature of inflammatory disorders has made the identification of a specific cause particularly challenging, however it is generally considered that a combination of genetic and environmental factors is involved in promoting disease pathogenesis [3]. To elicit an immune response BfUbb must be exposed to the immune system and environmental factors such as exposure to mercury, pesticides and persistent organic pollutants as well as poor lifestyle habits including cigarette smoking and excessive alcohol consumption are also thought to play a role in autoimmune disease development. The intestinal epithelium is essential in acting as a physical barrier between harmful environmental material and the host’s systemic circulation [4]. As BfUbb is produced by bacteria in the gut lumen it must gain entry to the circulatory system and environmental factors could contribute to this. The aim of this project is to investigate the impact both the molecular mimic, BfUbb, and circulating antibodies to it, have on host cells. The project will entail cultivating BfUbb producing strains of B. fragilis, harvesting extracellular vesicles which harbour BfUbb and investigating their impact on cells. This will require development of a cell line or organoid model and which will be combined with high content analysis to determine impact on cell health. Previous research has mapped the unique and shared epitopes of BfUbb and these will be used to investigate sera samples obtained from patients suffering from autoimmune conditions.
[1] Jiang, K., Li, W., Tong, M. et al. Bacteroides fragilis ubiquitin homologue drives intraspecies bacterial competition in the gut microbiome. Nat Microbiol (2023)
[2] Stewart, L., Edgar, D., Blakely, G. & Patrick, S. 2018. Antigenic mimicry of ubiquitin by the gut bacterium Bacteroides fragilis: a potential link with autoimmune disease. Clinl Exp Immunol. 194: 153–165
[3] English, J., Patrick, S. & Stewart, L.D. (2023) The Potential Role of Molecular Mimicry by the Anaerobic Microbiota in the Aetiology of Autoimmune Disease. Anaerobe 80 102721
[4]English, J., Connolly, L., & Stewart, L. D. (2023) Increased Intestinal Permeability: An Avenue for the Development of Autoimmune Disease? Exposure and Health doi.org/10.1007/s12403-023-00578-5

Postgraduate Research applicants who are interested in applying for this fully funded studentship must have applied to Queen’s University Belfast, via the Direct Applications Portal (link below), and submitted all required supporting documents by the closing date: https://dap.qub.ac.uk/portal/user/u_login.php For further information about academic requirements please see below: https://www.qub.ac.uk/courses/postgraduate-research/biological-sciences-phd.html

Funding Information

Funded by the Department for the Economy (DfE). For UK domiciled students the value of an award includes the cost of approved tuition fees and maintenance support the 2024/25 rates are still to be confirmed (current rates for 2023/24 are Fees £4,712, Stipend £18,622). To be considered eligible you must have been ordinarily resident in the UK for the full 3-year period prior to the start of the studentship and you must be ordinarily resident in Northern Ireland on the first day of the start of the studentship. For further information about eligibility criteria please refer to the DfE Postgraduate Studentship Terms and Conditions at https://www.economy-ni.gov.uk/publications/student-finance-postgraduate-studentships-terms-and-conditions

Project Summary
Supervisor

Dr Linda Stewart

More Information

askmhls@qub.ac.uk

Research Profile


Mode of Study

Full-time: 3 Years


Funding Body
DfE
Apply now Register your interest

Biological Sciences overview

The School of Biological Sciences provides PhD and MPhil (research degree) programmes in subjects ranging from basic biochemistry, molecular genetics and cancer research, to agricultural science, marine ecology and the economic evaluation of ecosystem services and food retailing. If you have a topic or research question in mind, please use the Find a Supervisor link (see Apply tab) to identify the most appropriate member of staff to support your idea. If not, don't worry, we regularly advertise funded projects and there is no harm in browsing our academic staff profiles for inspiration and then contacting whoever seems best: we are very open to applications from suitably qualified people interested in scientific research. In every case, a PhD or MPhil course provides the means of being part of a cutting edge scientific research team and contributing to genuine new discoveries or the development of new methods for practical use. If you cannot study full time, we offer pro-rata part time research degree programmes as well.

There are three broad themes to research at the School:

- Agri-Food Systems and Human Nutrition
- Understanding Health and Disease
- Sustaining Ecosystems and Biodiversity

Agri-Food Systems and Human Nutrition:

This theme focuses on how Agri-Food systems can be better positioned to provide safe, authentic and healthy diets with high-quality plant, livestock, and aquaculture products, whilst supporting human and animal health in a way that is sustainable and resilient to climactic changes.

Underpinning these goals, the disciplinary expertise of the theme integrates basic and applied research from animal health and welfare, nutrition, performance, and environmental and social impact (e.g. greenhouse gas emissions from livestock) to chemical contaminant and natural toxin detection, food microbiology, food fraud detection, and food systems traceability and transparency, integrated into a holistic total systems approach.

Supporting by underpinning expertise in cutting-edge molecular, genomic, transcriptomic, proteomic, and metabolomic technologies, artificial intelligence and simulation modelling, the goal of the theme is to support the transformation of global Agri-Food systems. This is with the purpose of maximising the benefits both to animal and human nutrition and health, while simultaneously reducing environmental impact, protecting ecological resources, supporting livelihoods and access to affordable safe foods, and upholding social, cultural, and ethical values. A system based on the principles of measurable integrity and impact.

Understanding Health and Disease:

The Understanding Health and Disease research theme covers humans, plants, and animals with research strengths in prevention, diagnostics, surveillance, epidemiology, and treatments. We study how health can be improved through food and nutrition and how diseases can be tackled by understanding their fundamental molecular mechanisms, including those underpinning the biology of pathogens and parasites. Our researchers work in human cancer and genetic diseases, in infections caused by bacteria, fungi, viruses, and parasites, and in how global health and disease will be affected by global warming and climate change.

We recognize that the only way to tackle the problems we face as a society is to take an interdisciplinary approach to our research. This means we have expertise in broad areas including molecular biology, biochemistry, bioinformatics, genomics, transcriptomics, modelling, bioanalytical chemistry, proteomics, metabolomics, microbiology, parasitology, and plant biology. We work internationally with researchers and partners in universities, charities, non-governmental organisations, industry, and government agencies to tackle local and global challenges.

Sustaining Ecosystems and Biodiversity:

This theme covers research in biodiversity and ecosystem services for environments ranging from tropical forests to deep oceans, using field techniques and skills such as wildlife tracking, taxonomy, geostatistics, molecular and genetic ecology, environmental microbiology, microbial ecology, food web analysis, microcosm and mesocosm experiments, and mathematical/computational methods. Within this theme we also study the behaviour and temperament of wild, agricultural or domestic animals and their implications for welfare and ability to respond to environmental change.

Potential research projects include phylogenetic analysis of rare and newly discovered species, examination of ecological interactions in tropical systems, agricultural soils, or marine communities, using state-of-the-art genetic analysis, surveys using drones or satellite tagging, or experiments in tanks and field plots, including careful and ethical examinations of animal behaviour. Projects range from theoretical analysis of stability in ecosystems, through discovery of new species and mechanisms of interaction, or responses to climate change, to the assessment of agri-environment schemes, development of new methods for commercial fisheries management and economic evaluations of conservation measures. Projects very often have an international dimension and include collaboration with other researchers worldwide.

Biological Sciences Highlights
Industry Links
  • The School has a wide range of strong, international links with governments, academia and industry, into which postgraduate research students are integrated.
World Class Facilities
  • Research students will have access to laboratory space as required (in our state-of-the-art research laboratories) and where relevant, also a range of field study sites and equipment (e.g. remote sensing drone equipment). They also have access to local and campus-wide high performance computing facilities and the full strength of our world-class library. Many students also benefit from the strong collaboration network maintained by our academic staff, which could result in working in the laboratories of partner organisations in industry and government as well as in the University, under specific arrangements.
  • Students studying in the Food Safety and Nutrition programme will gain excellent practical experience of advanced technology and bioanalytical techniques for food safety analysis and monitoring, including:

    1. GC, HPLC and UPLC separation platforms;
    2. ICP, IR, qToF and QqQ mass spectrometers;
    3. Microbiological research facilities;
    4. Antibody production and biomolecule binder development;
    5. Cell culture suite and bioanalytical assay detection systems;
    6. NMR, NIR and Raman spectrometers;
    7. Proteomic and metabolomic profiling tools RT-PCR;
    8. Transcriptomic profiling;
    9. Next-generation sequencing;
    10. Multiplex biosensor platforms and LFD development.
Internationally Renowned Experts
  • Research at Institute for Global Food Security and the School of Biological Sciences was rated 1st in the UK in the latest Research Exercise Framework (REF) – an independent assessment of research quality, impact and environment at UK universities.

    IGFS/Biological Sciences topped the national league table for Agriculture, Veterinary and Food Science, with 94% of research in those areas deemed “world-leading” or “internationally excellent”.

    Additionally, the research environment at IGFS/SBS scored a phenomenal 100%.
Key Facts

  • Most of the critical problems facing humanity - disease, climate change and food security - require biological understanding to solve them.

Course content

Research Information

PhD Supervisors
Information on the research interests and activities of academics in Biological Sciences can be accessed via the School website and the Find a Supervisor facility (see Apply tab).

Career Prospects

Introduction
Queen's postgraduates reap exceptional benefits. Unique initiatives, such as Degree Plus and Researcher Plus bolster our commitment to employability, while innovative leadership and executive programmes alongside sterling integration with business experts helps our students gain key leadership positions both nationally and internationally. Career prospects in the biological sciences are exceptionally good. To some extent it depends on the specific topic, of course, but laboratory-based and especially quantitative skills and the proven innovation of a PhD or MPhil are highly sought after. Degrees are very much in demand, both in commercial science and public sector research and development (e.g. drug discovery and development, crop and animal improvements and welfare, sustainable agriculture and resource use, human nutrition and health, animal health, ecological management, food safety and technology, scientific communications, regulation, and many more fields).

Employment after the Course
Graduates have gone on to be professional research scientists, consultants, or hold technical and junior executive positions in commerce and government.

People teaching you

Dr Gareth Arnott
Postgraduate Research Director
School of Biological Sciences
For a PhD you will have a principal and second supervisor who advise your independent studies and will be supported by a wider team from the academic staff - who they are, of course, depends on your project. For further details on any aspect of postgraduate research degrees within the School of Biological Sciences, contact: biosciences-pg@qub.ac.uk. Research degrees are overseen by the School of Biological Sciences Director of Postgraduate Research, who currently is Dr Gareth Arnott.

Learning Outcomes
A postgraduate research degree involves the undertaking of independent research under the guidance of a professional academic supervisory team, typically using the laboratory facilities on offer in one or more of the teams' labs. The student will be expected to develop their own ideas and learn the methods needed to test them empirically and theoretically. This usually involves learning and practising both laboratory (and or field) skills as well as developing a strong theoretical background in the relevant subject.

As well as practical work, all the activities of independent academic scholarship, such as literature searching and critical appraisal, written and verbal communications and academic networking will be developed during a research degree. Independence and innovation will be strongly encouraged, but the student will be supported by regular supervisory guidance and a wide range of courses will also be on offer, both in subject specific skills and generic skills, especially supported by the Graduate School (https://www.qub.ac.uk/graduate-school/).

Students are encouraged to interact with one another and with members of academic staff and postdoctoral scientists to build confidence and informal learning, through a range of ‘research culture’ activities, including peer groups where students get together to discuss topical research papers, or methods, or just chat about their interests.
Course structure
Research degrees vary in length, but typically for a PhD they are three or four years long (full-time) and double that for part-time studies. They follow an annual cycle of progress with formal panel-based appraisals of the progress, the outcome of which is typically practical and academic advice about how to overcome problems encountered and how to move to the next stage. During each year, students are expected to supplement their studies with some tailored courses, ranging from highly specific (e.g. learning to use a piece of apparatus or technique) to generic (e.g. developing oral presentation or leadership skills). Every stage is supported by the supervisory team, augmented by an independent panel of progress monitors as well as the full support of the Graduate School.
Assessment

Assessment processes for the Research Degree differ from taught degrees. Students will be expected to present drafts of their work at regular intervals to their supervisor who will provide written and oral feedback; a formal assessment process takes place annually.

This Annual Progress Review requires students to present their work in writing and orally to a panel of academics from within the School. Successful completion of this process will allow students to register for the next academic year.

The final assessment of the doctoral degree is both oral and written. Students will submit their thesis to an internal and external examining team who will review the written thesis before inviting the student to orally defend their work at a Viva Voce.

Feedback

Supervisors will offer feedback on draft work at regular intervals throughout the period of registration on the degree.

Facilities

Full-time research students will have access to a desk in a shared office space.

Entrance requirements

Graduate
The minimum academic requirement for admission to a research degree programme is normally an Upper Second Class Honours degree in a relevant subject from a UK or ROI HE provider, or an equivalent qualification acceptable to the University. Further information can be obtained by contacting the School.

International Students

For information on international qualification equivalents, please check the specific information for your country.

English Language Requirements

Evidence of an IELTS* score of 6.5, with not less than 5.5 in any component, or an equivalent qualification acceptable to the University is required (*taken within the last 2 years).

International students wishing to apply to Queen's University Belfast (and for whom English is not their first language), must be able to demonstrate their proficiency in English in order to benefit fully from their course of study or research. Non-EEA nationals must also satisfy UK Visas and Immigration (UKVI) immigration requirements for English language for visa purposes.

For more information on English Language requirements for EEA and non-EEA nationals see: www.qub.ac.uk/EnglishLanguageReqs.

If you need to improve your English language skills before you enter this degree programme, INTO Queen's University Belfast offers a range of English language courses. These intensive and flexible courses are designed to improve your English ability for admission to this degree.

Tuition Fees

Northern Ireland (NI) 1 TBC
Republic of Ireland (ROI) 2 TBC
England, Scotland or Wales (GB) 1 TBC
EU Other 3 £25,600
International £25,600

1 EU citizens in the EU Settlement Scheme, with settled or pre-settled status, are expected to be charged the NI or GB tuition fee based on where they are ordinarily resident, however this is provisional and subject to the publication of the Northern Ireland Assembly Student Fees Regulations. Students who are ROI nationals resident in GB are expected to be charged the GB fee, however this is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.

2 It is expected that EU students who are ROI nationals resident in ROI will be eligible for NI tuition fees. The tuition fee set out above is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.

3 EU Other students (excludes Republic of Ireland nationals living in GB, NI or ROI) are charged tuition fees in line with international fees.

All tuition fees quoted are for the academic year 2021-22, and relate to a single year of study unless stated otherwise. Tuition fees will be subject to an annual inflationary increase, unless explicitly stated otherwise.

More information on postgraduate tuition fees.

Biological Sciences costs

Students may incur additional costs for small items of clothing and/or equipment necessary for lab or field work

Additional course costs

All Students

Depending on the programme of study, there may also be other extra costs which are not covered by tuition fees, which students will need to consider when planning their studies . Students can borrow books and access online learning resources from any Queen's library. If students wish to purchase recommended texts, rather than borrow them from the University Library, prices per text can range from £30 to £100. Students should also budget between £30 to £100 per year for photocopying, memory sticks and printing charges. Students may wish to consider purchasing an electronic device; costs will vary depending on the specification of the model chosen. There are also additional charges for graduation ceremonies, and library fines. In undertaking a research project students may incur costs associated with transport and/or materials, and there will also be additional costs for printing and binding the thesis. There may also be individually tailored research project expenses and students should consult directly with the School for further information.

Bench fees

Some research programmes incur an additional annual charge on top of the tuition fees, often referred to as a bench fee. Bench fees are charged when a programme (or a specific project) incurs extra costs such as those involved with specialist laboratory or field work. If you are required to pay bench fees they will be detailed on your offer letter. If you have any questions about Bench Fees these should be raised with your School at the application stage. Please note that, if you are being funded you will need to ensure your sponsor is aware of and has agreed to fund these additional costs before accepting your place.

How do I fund my study?

1.PhD Opportunities

Find PhD opportunities and funded studentships by subject area.

2.Funded Doctoral Training Programmes

We offer numerous opportunities for funded doctoral study in a world-class research environment. Our centres and partnerships, aim to seek out and nurture outstanding postgraduate research students, and provide targeted training and skills development.

3.PhD loans

The Government offers doctoral loans of up to £26,445 for PhDs and equivalent postgraduate research programmes for English- or Welsh-resident UK and EU students.

4.International Scholarships

Information on Postgraduate Research scholarships for international students.

Funding and Scholarships

The Funding & Scholarship Finder helps prospective and current students find funding to help cover costs towards a whole range of study related expenses.

How to Apply

Apply using our online Postgraduate Applications Portal and follow the step-by-step instructions on how to apply.

Find a supervisor

If you're interested in a particular project, we suggest you contact the relevant academic before you apply, to introduce yourself and ask questions.

To find a potential supervisor aligned with your area of interest, or if you are unsure of who to contact, look through the staff profiles linked here.

You might be asked to provide a short outline of your proposal to help us identify potential supervisors.

Download Postgraduate Prospectus