PhD studentships for Early Stage Researchers (< 4 years experience)

• Medical University of Vienna - all vacancies filled
  
• University of Cambridge - all vacancies filled
  
• Trinity College Dublin - all vacancies filled
  
• Hycult Biotech, Uden, NL - vacancy filled
  

Medical University of Vienna - all vacancies filled

Project 1 - Anti-hlamp-2 antibodies and macrophages and DC function (Supervisor: Prof Andy Rees)

This project will characterize the effect of antibodies to LAMP-2 on macrophage and dendritic cell activation and function. Specific experiments will examine how anti-LAMP-2 antibodies influence (i) monocyte differentiation, DC maturation and macrophage activation; (ii) induction of autophagocytosis and susceptibility to apoptosis; and (iii) antigen presentation. Monocyte gene expression induced by anti-LAMP-2 antibodies in vitro will be compared to monocyte transcriptomic patterns of patients with AASV. These studies will determine whether antibodies to LAMP-2 activate macrophages and provide insight into the pathogenesis of AASV.  
Methodology: Cell culture, light, fluorescent and confocal microscopy; expression arrays; quantitation of cytokines; quantitative assessment of apoptosis and autophagocytosis.
Attachments/Collaborations:
(1) P3 - LUMC) to learn isolation and analysis of Dendritic Cells (Year 1);
(2) P2 - UCAM for comparative transcriptomics (Year 2).

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Project 2 - Endothelial cell death induced by antibodies to hLAMP-2 (Supervisor: Dr Renate Kain)

This project will characterize the mechanism by which antibodies to hLAMP-2 activate endothelial cells using an immortalized human glomerular endothelial cell line (GEnC) as a model. The ESR will quantify cellular uptake and subcellular distribution of anti-LAMP-2 antibodies and their effects on apoptosis and autophagy. These experiments will provide the foundation for analysing the effects of anti-LAMP-2 antibodies on angiogenesis using the ex vivo model systems developed by partner 6 (AstraZeneca). These experiments should provide an insight into the relation between anti-LAMP-2 antibodies and tissue injury in vasculitis.
Methodology: Cell culture; immunohistochemistry; transmission electron microscopy and immunoelectron microscopy; quantification of autophagocytosis/apoptosis; angiogenesis assays.
Attachments/Collaborations:
(1) P6 - AstraZeneca: learning and application of angiogenesis assays at the end of year 2.

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Project 3 - Lymphangiogenesis and the control of renal inflammation (Supervisor: Prof Dontscho Kerjaschki)

This project will undertake a systematic immunohistological analysis of CD4+ T cells within the tertiary lymphatic organs of human transplanted kidneys in order to determine:

(i) the frequency of activated FoxP3+ regulatory T cells within them;
(ii) their relationship to the lymphatic endothelium of donor origin; and
(iii) finally their interactions with renal dendritic cells and macrophages. This will provide the foundation collaborative experiments with H-J Gröne (Heidelberg) in which lymphangiogenesis will be studied in renal allografts in mice to determine the consequences of interruption of pathways responsible for lymphangiogenesis systematically.
Methodology: Immunohistochemistry, electron microscopy and immunoelectron microscopy. In vivo models of renal transplantation.
Attachments/Collaborations:
(1) P6 - AstraZeneca: learning and application of angiogenesis assays in year 2.
(2) (Heidelberg): renal allografts in mice.

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Project 4 - Immunity to LAMP-2 and other glomerular antigens (Supervisor: Prof Andy Rees)

This project will analyze the relations between immunity to LAMP-2 and immunity to other glomerular targets in causing injury in FNGN both in vivo. The ESR will perform specific experiments to determine whether active or passive immunity to LAMP-2 synergistically increases injury caused by sub-nephritogenic levels of immunity to the MPO or the GBM. When appropriate, mechanisms of the interaction will be elucidated using reagents developed by collaborators within and without the network. The results will provide a deeper insight into injury in FNGN and should provide a platform for new therapeutic approaches.
Methodology: Generation of recombinant antigens and purification of native and recombinant antigens; tissue culture; induction and analysis of rodent models of FNGN.
Attachments/Collaborations:
(1) P3 analysis of leukocyte infiltrates;
(2) P4 testing novel inhibitors;

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Contact: Gertrude Krainz; email: gertrude.krainz[at]meduniwien.ac.at

University of Cambridge - all vacancies filled

Project 1 - Predicting the response in inflammatory vascular disease (Supervisor: Prof Ken Smith)

This project will determine whether transcriptomic analysis of peripheral blood mononuclear cells predicts the response to immunosuppressive therapy in patients with systemic autoimmune disease. The ESR will compare transcriptomic data at presentation and after three months therapy and relate the results to clinical response of patients. Novel bioinformatics tools will be used to search for transcriptomic patterns that correlate with disease outcome of in patients with various types of small vessel vasculitis and to determine whether they can be used to guide therapy.
Methodology: Human peripheral blood cell separations; RNA extraction; processing microarrays arrays; bioinformatics.
Attachments/Collaborations:
(1) P1 - MUW: comparison of peripheral blood and renal microarray data in AASV.
(2) (EMBL-EBI, Hinxton, UK): microarray informatics.

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Project 2 - Transcriptomics to predict renal transplantation rejection (Supervisor: Prof Ken Smith)  

This project will examine an identified transcriptomic signature that correlates with frequent relapse in small vessel vasculitis also predicts outcome in renal transplantation. Leucocyte subset specific transcriptomic analysis will be performed on peripheral blood mononuclear cells taken from transplant recipients before and six days after transplantation. The transcriptomic data will be correlated with allograft rejection rate and other clinical parameters using novel bio-informatic tools and to determine whether the results can be used to guide immunosuppressive therapy.
Methodology: Study design, magnetic cell separation, RNA preparation, microarray hybridization, array informatics, RT-PCR validation, immune phenotyping using flow cytometry and in vitro lymphocyte function assays.
Attachments/Collaborations:
(1) Collaboration on microarray informatics with (EMBL-EBI, Hinxton, UK).

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Contact: Dr Paul Lyons; email: pal34[at]cam.ac.uk

 

Trinity College Dublin - all vacancies filled

Project 1 - Modulation of miRNA-21 by TLR in inflammation (Supervisor: Prof Luke O´Neill)

This project will characterize the naturally expressed microRNA, miR-21, as a target for toll-like receptor (TLR) signaling in vascular inflammation. The ESR will quantify miR21 induction after TLR ligation and map the signaling pathways responsible. Target mRNAs for miR21 will be identified and the importance of miR21 in vivo will be determined using in models of vascular inflammation in genetically deficient mice.
Methodology: Biochemical and cell biological analysis of intracellular signaling; assessment of gene expression; and the techniques for the functional analysis of miRNA.
Attachments/Collaborations:
(1) P3 - LUMC: In vivo experiments to test with effects of miR21 deficiency on models of vascular inflammation.  

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Contact: Ms Cait Donoghue; email: cdonoghu[at]tcd.ie

Hycult Biotech, Uden, NL - vacancy filled

Project 1 - Assessing biomarkers for vascular inflammatory disease (Supervisor: Dr Helma Rutjes)

This project will develop and characterize monoclonal antibodies against mouse complement proteins and use them to develop and standardize novel methods for analyzing of mouse complement activity. The assays will then be used quantify differences in levels of specific complement pathways in different mouse strains and to analyze complement activation in models of vascular inflammation. The results will provide a much needed link between murine models and clinical disease.
Methodology: Cell culture, ELISA, Western blotting, Recombinant protein technologies, Flow cytometry, PCR, Antibody generation, purification and modification.
Attachments/Collaborations:
(1) P3 -LUMC joint supervision and collaboration. 

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Contact: Dr Helma Rutjes; email: h.rutjes[at]hycultbiotech.com