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Metagenomics to investigate the role of bacteria and antibiotic resistance in respiratory disease


Department of Genetics and Genome Biology

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Dr J Morrissey , Prof S Siddiqui , Dr N Greening No more applications being accepted Funded PhD Project (European/UK Students Only)
Leicester United Kingdom Bioinformatics Immunology Microbiology Molecular Genetics

About the Project

The aim of this project is to identify causative pathogens and microbiome changes in clinical samples, using metagenomics to reduce antimicrobial resistance and to differentiate between the different causes of acute breathlessness (AB) to enable accurate personal treatment regimes.

This is an exciting interdisciplinary project combining highly successful clinical, metagenomics, metabolomics, molecular microbiology, computational biology and diagnostics research. The project can involve data analysis and laboratory-based research and can be flexible to the interests and expertise of the student.

Acute Breathlessness is a common life-threatening feature of community acquired pneumonia, asthma and COPD exacerbations. It is known that these illnesses are complex and can include imbalance of the natural microbial community (microbiome) and infection by a variety of different organisms.

Understanding of the role of microbes in AB is very limited, but alterations within the microbiome, or growth of pathogens, are believed to cause COPD exacerbations. In community acquired pneumonia, the actual microbial agent is unidentified in 30-65% of cases. In both these illnesses identification of indicative microbiome changes or a causative agent, is crucial for optimal patient care and reducing antibiotic resistance.

The samples for this project come from the EMBER research programme (Ibrahim et al 2020) which has gathered full clinical data, including breath volatile organic compounds (VOCs), in addition to a series of clinical samples. Samples were obtained from patients with AB within 24 hours of acute admission. Metagenomics of the samples from these patients will identify infectious pathogens, and imbalance of the microbiome, whereas metabolomics will identify VOC signals associated with COPD and pneumonia. The novelty of this study is to compare these two different signals to increase understanding of respiratory disease.

The cause and effect on patient treatment responses of these changes in the microbial community and the impact on the metabolome signal are not understood and need to be further investigated with greater computational analysis and complementary mechanistic studies, and is the aim of this project.

Objectives are to:

  1. Determine differences in microbial diversity associated with different causes of acute breathlessness.
  2. Identify infectious agents, virulence and antimicrobial genes associated with COPD or community acquired pneumonia.
  3. Determine the association between metagenomic and metabolomic signal and patient.

Expected outcomes and training

This is a highly innovative and unique project based on clinical research of pneumonia, COPD and acute care, and microbial research on the interactions between the environment, bacteria and the host.

The student will be supervised by a clinical (Siddiqui, Greening) and non-clinical (Morrissey) and biostatistical/bioinformatics (Richardson) supervisory team and be well-provided with all the necessary training and facilities.

The student will have access to training in molecular microbiology, computational biology (e.g. bioinformatics) and clinical research. The student will also benefit from being part of large inter-disciplinary projects on air pollution and bacteria, and clinical research on COPD and asthma. Regular research meetings between the clinical and discovery science groups will greatly support the student.

Metagenomics combined with metabolomics will dramatically increase our understanding of how the microbiome and pathogens are involved in causing these acute respiratory diseases as well as inform on virulence factors and antibiotic resistance. This project has the potential for high impact in diagnostics, clinical research, and molecular microbiology.

Entry requirements:

Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better, or overseas equivalent in a relevant subject. 

The University of Leicester English language requirements apply where applicable.

Application advice:

To apply please refer to: https://le.ac.uk/study/research-degrees/funded-opportunities/lemid-morrissey-2021

Project enquiries: Professor Julie Morrissey ([Email Address Removed])

Application enquiries to [Email Address Removed]


Funding Notes

This 3-year PhD studentship provides:
• UK/EU tuition fee waiver
• Annual stipend at UKRI rates (£15,609 for 2021/22)
• Research Training Support Grant of £5,000 per annum

References

Ibrahim W, et al. Thorax 2021;0:1–8. doi:10.1136/thoraxjnl-2020-215667


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