We are seeking for highly motivated candidates with strong academic background in immunology, chemistry, biology or related area for a multidisciplinary PhD project focused on discovering novel glycan structures that are capable of modulating the function of human antigen presenting cells with potential applications in vaccination and drug delivery. The project will be co-supervised by Professors Amir Ghaemmaghami (Faculty of Medicine and Health Sciences) and Morgan Alexander (School of Pharmacy).
Background and aims:
Antigen presenting cells (APCs) such as macrophages and dendritic cells act as a bridge between innate and adaptive immune system play a crucial rule in orchestrating immune responses to pathogens. The activation status of APCs can determine the outcome of an immune response and instruct the differentiation of T cells towards distinct functional subsets such as Th1, Th2, Th17 and regulatory T cells. Under physiological conditions, these T cell subsets are essential for mounting successful immune responses against different pathogens (e.g. bacteria, helminthic parasites, fungi, viruses etc.) as well as maintaining peripheral tolerance. However under pathological conditions their uncontrolled activation can lead to pathologies associated with autoimmune and allergic diseases.
Immune modulatory properties of carbohydrates are well established. For examples, different carbohydrate structures on antigens (from pathogens or allergens) interact with antigen presenting cells (through specific receptors called lectins) and can determine the outcome of immune responses by modulating the function of antigen presenting cells. Depending on their structure and which receptors they bind to different carbohydrate can bias immune responses towards pro-inflammatory, anti-inflammatory or regulatory phenotypes. Therefore the overall aim of this project is to use a combination of cellular immunology and high throughput screening/characterisation strategies to identify novel carbohydrates that are able to modulate the phenotype of human antigen presenting cells towards distinct functional phenotypes (e.g. pro-inflammatory, anti-inflammatory or regulatory). Such carbohydrates will have clinical applications in vaccination (e.g. as novel adjuvants), drug delivery and immunotherapy amongst others.
The project provides excellent training opportunities in cellular immunology techniques (e.g. working with dendritic cells, T cell, developing co-cultures, flow cytometry), ELISA, PCR, confocal microscopy as well as a diverse range of high throughput screening strategies as well as analytical and surface characterisation techniques (e.g. ToF-SIMs and high throughput microscopy).
Requirements: Applicants should have a First or 2.1 BSc in biology, chemistry, immunology or related disciplines. Previous laboratory based experience in a relevant area will be advantageous. Overseas applicants should fulfil the University of Nottingham English Language Requirements.
This post is suitable for self-funded applicants and is available immediately.
Applicants can contact Professor Ghaemmaghami ([email protected]) for informal enquiries
1- Glycans in immune recognition and response. Amon R, Reuven EM, Leviatan Ben-Arye S, Padler-Karavani V. Carbohydr Res. 2014 May 7;389:115-22. doi: 10.1016/j.carres.2014.02.004.
2- The role of lectins in allergic sensitization and allergic disease.
Salazar F, Sewell HF, Shakib F, Ghaemmaghami AM. J Allergy Clin Immunol. 2013 Jul;132(1):27-36. doi: 10.1016/j.jaci.2013.02.001.
3- Surface characterization of carbohydrate microarrays. Scurr DJ, Horlacher T, Oberli MA, Werz DB, Kroeck L, Bufali S, Seeberger PH, Shard AG, Alexander MR. Langmuir. 2010 Nov 16;26(22):17143-55. doi: 10.1021/la1029933.
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