The role of the IgM receptor FcmuR in malaria

Fcmu receptors binds to IgM and are expressed on B and T cell but their function is poorly understood. Several proteins encoded by Plasmodium falciparum bind to IgM and reduce binding of IgM to the Fcmu receptor. The candidate will investigate the role of the Fcmu receptor for B- and T cell function and how parasite proteins interfere with it.

Where does this project lie in the translational pathway

T1 – Basic Research in Medecine

 

 

 

The project will address a basic immunological question and utilise the acquired knowledge to understand how P. falciparum undermines the function of the Fcmu receptor. While it is too early to predict whether the outcomes of the research have any clinical application, they are likely to contribute to our knowledge on immune-evasion by P. falciparum and how this affects different disease outcomes.

 

Methodological aspects of the PhD project

The project offers a variety of laboratory techniques including cellular immunology, cell culture, recombinant protein production. Transcriptomic analysis of B and T cell modified by P. falciparum IgM-binding proteins will form part of the project with the aim to inform the development of vaccines or diagnostic tools targeting these proteins.

 

Expected outputs of the PhD project

Publications, further funding likely since the role of IgM and its receptors are relevant for other infections aside from malaria

 

External industry links or training opportunities available for the student

MRes project rotation with Absolute Antibodies  (to be confirmed)

 

Required skills/experience/aptitudes

Basic immunology

 

Key publications that relate to this proposed project

1.

Lloyd KA, Wang J, Urban BC, Czajkowsky DM, Pleass RJ (2017) Glycan-independent binding and internalization of human IgM to FCMR, its cognate cellular receptor.  Sci Rep. 7:42989. PMC53222398

2.

Crosnier C1, Iqbal Z2, Knuepfer E3, Maciuca S2, Perrin AJ1, Kamuyu G4, Goulding D5, Bustamante LY4, Miles A6, Moore SC7, Dougan G5, Holder AA3, Kwiatkowski DP6, Rayner JC4, Pleass RJ8, Wright GJ9 (2016) Binding of Plasmodium falciparum Merozoite Surface Proteins DBLMSP and DBLMSP2 to Human Immunoglobulin M Is Conserved among Broadly Diverged Sequence Variants. J Biol Chem. 2016 Jul 1;291(27):14285-99. doi: 10.1074/jbc.M116.722074. Epub 2016 May 12.

3.

Pleass RJ, Moore SC, Stevenson L, Hviid L.(2016) Immunoglobulin M: Restrainer of Inflammation and Mediator of Immune Evasion by Plasmodium falciparum Malaria. Trends Parasitol. 2016 Feb;32(2):108-19. doi: 10.1016/j.pt.2015.09.007. Epub 2015 Nov 18. Review.

4.

Muema, D.M, Macharia, G.N., Hassan, A.S., Mwaringa, S.M., Fegan, G.W., Berkley, J.A., Nduati, E.W., Urban, B.C. 2015. Control of viraemia enables acquisition of resting memory B cells with age and normalization of activated B cell phenotypes in HIV-infected children. Journal of Immunology 195, 1082-1091

5.

Gitau, E., Tuju, J., Karanja, H., Stevenson, L., Kimani, E., Olotu, A., Kimani, D.,Marsh, K., Urban, B.C. 2014. CD4+ T-cell responses to the Plasmodium falciparum Erythrocyte Membrane Protein 1 in children with mild malaria. Journal of Immunology 192, 1753-1761.

 

The deadline for applications is 23:59 on Tuesday 2nd January 2018. More information on this programme can be found here.

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