Download Anti-food polysaccharide antibody formation in Inflammatory

FMH-SF-13-01
Faculty of Medicine and Health Sciences Graduate School
School of study: Norwich Medical School
Department or Group: Department of Medicine/Gut Biology
Title: Anti-food polysaccharide antibody formation in Inflammatory Bowel
Diseases
Application Deadline: 15 November 2013
Interview Date: 19 December 2013
Start Date: 1 April 2014
Supervisory Team:
Primary: Professor Alastair Watson
Secondary: Dr Norihito Kawasake
Abstract of PhD project
Inflammatory bowel disease (IBD) is a chronic inflammatory disease affecting approximately 400
people per 100K populations in UK, which burdens the NHS with £720 million per annum (British
Society of Gastroenterology, 2009). It has been shown that IBD patients produce an abnormally
high level of antibodies against yeast polysaccharide such as ß-glucans. These antibodies may be
a factor triggering gut inflammation through over-activation of the gut immune system in IBD
patients.
In this project, we hypothesise IBD patients develop antibodies against other food polysaccharides
(anti-food polysaccharide antibody; AFPA). We suggest that disease exacerbation may occur by
eating food containing polysaccharide epitopes that stimulate antibody production. The student will
assess AFPA levels in serum samples from IBD patients using an ELISA-based assay.
Subsequent correlation study of the AFPA levels with IBD pathology will give insight to the
potential utility of AFPAs for IBD therapy, diagnosis, and prognosis.
We also aim to address the mechanism of the antibody formation. We hypothesize that the
immune cell lectins specific to the yeast polysaccharides initiate the antibody formation. The
hypothesis stems from the fact that binding of polysacchrides to the lectin partner results in
activation of the gut immune system (Sancho D et al, Annu Rev immunol, 2012). To prove our
hypothesis, the student will focus on Dectin-1, a ß -glucan binding lectin. Dectin-1 is expressed on
dendritic cells (DCs) and play key mediator roles in gut inflammatory response (Taylor PR et al,
Nat Immunol, 2007). The student will investigate the role of Dectin-1 in ß-glucan antibody
formation by using a mouse model (in vivo) and cellular models (in vitro).
References
1] Nycholat CM et al, In silico-aided design of a glycan ligand of sialoadhesin for in vivo targeting
of macrophages, J Am Chem Soc, 2012
[2] Moussata D et al, Confocal laser endomicroscopy is a new imaging modality for recognition of
intramucosal bacteria in inflammatory bowel disease in vivo, Gut, 2011
[3] Pfrengle F et al, Co-presentation of antigen and ligands of Siglec-G induces B cell tolerance
independent of CD22, J. Immunol., 2013
FMH-SF-13-01
[4] Kawasaki N, Rademacher C, Paulson JC, CD22 regulates adaptive and innate response of B
cells, Journal of innate immunity, 2011
Entry Requirements
Applicants should hold a 2:1 degree or above or a master's degree in biology or equivalent
Those applicants whose first language is not English must demonstrate evidence of appropriate
English language proficiency, normally defined as a minimum IELTS score of 6.5 (Overall Band
Score) with 6.0 in all elements or equivalent.
Funding:
This project is open to applicants who are self-funded or have external sponsorship to cover fees,
living costs and annual project costs of £5,000 per annum associated with the project. Overseas
applicants may be eligible for an international bursary of £5,000 to £15,000 per annum
Making Your Application:
Please apply via the University’s online application system.
To discuss the application process, please contact the: Admissions Office, email:
[email protected] or telephone +44 (0)1603 591709.
To discuss the specific project, please contact the primary or secondary supervisors via their
email.