About the Project
New insights into the intracellular control of allergic effector cell function
University of Kent – Medway School of Pharmacy
A PhD position for 3 years is available starting in October 2016 within the School of Pharmacy, University of Kent in collaboration with Imperial College London. The candidate will be supervised by Dr Bernhard Gibbs (University of Kent; Main supervisor) and Dr Paul Turner (Imperial College London; Second supervisor).
The research aims of this project are to elucidate key intracellular signalling pathways involved in allergic responses that determine the degree of basophil reactivity to allergen provocation.
This project focusses on basophils, cells which crucially contribute to the symptoms of allergy by rapidly releasing histamine, eicosanoids and pro-inflammatory cytokines. The reactivity of these cells to allergen provocation closely correlates with the severity of allergic reactions, particularly in food allergies which can result in fatal anaphylactic shock. However, the mechanisms responsible for differential basophil activation are unclear and this has hampered attempts to predict symptom severity (resulting in considerable impact on patient quality of life). Project objectives include correlating mediator releases with the biochemical activity of stimulatory and inhibitory intracellular signalling pathways in purified human basophils obtained from healthy and allergic donors and stimulated with anti-IgE (which mimics allergen provocation). Further objectives include identifying biocompatible and non-toxic signal transduction modulators that could be considered for future anti-allergic therapy. This project could ultimately help identify intracellular signals that serve as predictors of allergy symptom severity and be used as potential therapeutic targets.
The project will involve purifying primary human basophils from blood by immunomagnetic selection, Western blot analysis, quantitative real-time PCR, ELISA, luminometric & fluorometric assays and FACS.
Funding Notes
Funding covers UK/European tuition fees and an annual stipend (£14,296). Applications will be considered from outstanding individuals with a background in a relevant discipline including biological or medical sciences. The equivalent of a first or upper second-class degree and basic research/laboratory experience is essential. Experience with human cell culture, FACS, RT-PCR and Western Blotting would be an advantage but not essential.
Applications should include a full CV, cover letter and the names/addresses of potential referees either emailed or sent to Dr Bernhard Gibbs, Medway School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, Kent, ME4 4TB.
Closing date: 31/03/2016
References
1) Gibbs BF, Gonçalves-Silva I, Prokhorov A, Abooali M, Yasinska I, Casely-Hayford M, Fasler-Kan E, Sumbayev V: Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via inhibition of the mTOR pathway and xanthine oxidase activity. Oncotarget, 6(30):28678-28692. doi: 10.18632/oncotarget.5212 (2015).
2) Mizrahi S, Gibbs BF, Karra L, Ben-Zimra M, Levi-Schaffer F: Siglec-7 is a Major Inhibitory Receptor on Human Mast Cells but not on Basophils. J. Allergy Clin. Immunol., May 5. pii: S0091-6749(14)00455-2. doi: 10.1016/j.jaci.2014.03.031 (2014).
3) Gibbs BF, Yasinska IM, Calzolai L, Gilliland D, Sumbayev VV: Highly Specific Targeting of Human Leukocytes using Gold Nanoparticle-Based Biologically Active Conjugates. J. Biomed. Nanotechnol. 10:1259-1266 (2014).
4) Gibbs BF, Sabato V, Bridts CH, Ebo DG, Ben-Zimra M, Levi-Schaffer F: Expressions and inhibitory functions of CD300a receptors on purified human peripheral blood basophils. Exp. Dermatol, 21:884-885 (2012).
5) Sumbayev, V. V., Nicholas, S. A., Streatfield, C. L., Gibbs, B. F. Involvement of Hypoxia-Inducible Factor-1 in IgE-Mediated Primary Human Basophil Responses. (2009) Eur. J. Immunol. 39, 3511-3519.
6) Gibbs BF, Papenfuss K, Falcone FH: A Rapid Two-Step Procedure for the Purification of Human Peripheral Blood Basophils to Near Homogeneity. Clin. Exp. Allergy, 38:480-485 (2008).
7) Gibbs BF, Räthling A, Zillikens D, Huber M, Haas H: Initial signal strength controls basophil Fc RI-mediated signaling which is down-regulated by SH2 domain-containing inositol 5-phosphatase. J. Allergy Clin. Immunol., 118: 1060-1067 (2006).
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