Assessing the Contributions of the Phase-Variable Sialic Acid and Phosphorylcholine Epitopes of Non-Typeable Haemophilus influenzae to Immunoevasion during Chronic Infections


   Department of Genetics and Genome Biology

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  Prof Chris Bayliss, Prof Chris Brightling, Dr Chris Holmes  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Additional Supervisor: Prof. Luisa Martinez-Pomares, University of Nottingham

Non-typeable Haemophilus influenzae (NTHi) significantly contribute to human disease including chronic obstructive pulmonary disorder (COPD). This complex disease involves numerous host immune modulators. Replication of NTHi bacteria in the diseased lung is associated with chronic disease but it is not clear how these bacteria survive host immune responses. Multiple NTHi genes undergo rapid ON and OFF switching, called phase variation (PV), due to hypermutable repetitive DNA tracts. Two phase-variable genes drive addition of negatively (sialic acid) and positively (phosphorylcholine) charged epitopes onto the lipooligosaccharide. These molecules influence bacterial interactions with host immune cells. This project focuses on investigating how PV affects immune evasion in model systems and clinical samples from chronic disease patients. Led by Prof. Chris Bayliss and Dr. Chris Holmes, molecular approaches will be utilized to monitor whether NTHi PV facilitates immune evasion. Immunological assays, such as resistance to neutrophils, will be developed during sessions at the University of Nottingham with Prof. Luisa Martinez-Pomares. Analysis of clinical COPD samples will be overseen by Prof. Chris Brightling. These studies will help explain the extent to which PV of surface molecules underlies elicitation of host immune responses and ability of NTHi to survive and cause inflammation in complex chronic diseases

Enquiries

Project Enquiries to [Email Address Removed]

Programme enquiries to [Email Address Removed]

To apply please refer to

https://more.bham.ac.uk/mrc-aim/phd-opportunities/


Biological Sciences (4) Chemistry (6) Engineering (12) Mathematics (25) Medicine (26)

Funding Notes

The competition funding provides students with:
4 years of stipend at UKRI rates
4 years of tuition fees at UK fee rates (Plus one award of a full overseas fee waiver to an international applicant)*
RTSG
Budget to help with the cost of purchasing a laptop
The University of Leicester will provide full overseas fee waivers for the duration of their study to all international students accepted at Leicester. The funder, UKRI, allows us to appoint up to 30% overseas students.

References

1. Moxon, Bayliss, Hood (2006) Annu Rev Genet 40: 307-333; 2. Identification of a bifunctional lipopolysaccharide sialyltransferase in Haemophilus influenzae: incorporation of disialic acid. Fox et al. (2006) J Biol Chem 281 p40024-32; 3. Bacterial exploitation of phosphorylcholine mimicry suppresses inflammation to promote airway infection. Hergott et al. (2015) 125 p3878-3890. 4. Serum IgM and C-Reactive Protein Binding to Phosphorylcholine of Nontypeable Haemophilus influenzae Increases Complement-Mediated Killing. Langereis et al. Infect Imm. 2019;87:e00299-19. 5. Relative contributions of lipooligosaccharide inner and outer core modifications to nontypeable Haemophilus influenzae pathogenesis. Morey et al. Infect Imm. 2013;81:4100-11.