25/03/2021
Marie Skłodowska-Curie Actions

EDUC8 : Call for applications from Early Stage Researchers for 1 Doctoral (PhD) Training Position in basic and translational immunology. Induction of tolerance to therapeutic FVIII by harnessing the tolerogenic potency of the liver


  • ORGANISATION/COMPANY
    Stichting Sanquin Bloedvoorziening-Sanquin (The Netherlands)
  • RESEARCH FIELD
    Biological sciencesBiology
    Medical sciencesOther
  • RESEARCHER PROFILE
    First Stage Researcher (R1)
  • APPLICATION DEADLINE
    30/04/2021 23:00 - Europe/Brussels
  • LOCATION
    Netherlands › Amsterdam
  • TYPE OF CONTRACT
    Temporary
  • JOB STATUS
    Full-time
  • HOURS PER WEEK
    40
  • OFFER STARTING DATE
    01/06/2021
  • EU RESEARCH FRAMEWORK PROGRAMME
    H2020 / Marie Skłodowska-Curie Actions
  • MARIE CURIE GRANT AGREEMENT NUMBER
    859974

OFFER DESCRIPTION

EDUC8 is an Innovative Training Network (ITN) funded by the European Union Horizon 2020 Programme. The EDUC8 training network represents a novel, pioneering platform for studying the immunogenicity of therapeutic pro-coagulant factor VIII (FVIII) in patients with haemophilia A (HA). It includes leading scientists from academia and industry. The EDUC8 training network offers doctoral research projects (PhD projects) for eight early stage researchers (ESRs). The research topics range from fundamental to translational science, and aim at identifying drug- and patient-related risk factors for the development of neutralizing anti-FVIII antibodies, and at developing innovative protocols for inducing tolerance to FVIII. The successful applicants will receive training in basic immunology, haemostasis research and bioinformatic approaches, clinical haemostasis, project management, entrepreneurship, healthcare economics, ethics and marketing. The interaction between biologists, clinical experts, healthcare professionals, industry and patients’ organizations is central to EDUC8. It will expose ESR to complex issues in bench-to-bedside research from different perspectives. Graduates from EDUC8 will be highly skilled, entrepreneurial and broadly-trained experts, equipped with innovative and beyond state-of-the-art proficiency on the exponentially expanding area of “immunogenicity of biotherapeutics”.

Participating in EDUC8 offers early stage researchers many unique opportunities, including:

  • A project as Marie Skłodowska Curie trainee in one of the participating institutions with the intention of receiving a doctoral degree (PhD).
  • State-of-the art, exciting research in an international consortium with highly integrated research projects.
  • Expert training in basic and translational immunology.
  • At least three months of research training in the lab of another consortium member, mostly in a different EU country than the country where most of the project will take place.
  • Training in both academic and commercial research environments.
  • Salary according to EU guidelines for Marie Skłodowska Curie trainees, including mobility payments and family allowances where applicable.

Eligible candidates must:

  • hold a Master’s degree or equivalent in a field of science relevant to their chosen project (see below)
  • demonstrate a history of academic excellence
  • demonstrate an affinity for Basic Immunology and Translational Immunology, Haemostasis or Translational Research
  • speak and write fluently in English
  • have less than 4-years previous research experience and not hold a doctoral (PhD) title
  • have not been resident in the Netherlands where the host institution is located for more than 12 months in the 3 years before recruitment
  • be available to start the project no later than 1st June 2021

Individual Projects details

ESR7 Induction of tolerance to therapeutic FVIII by harnessing the tolerogenic potency of the liver

Hosting Institution: Stichting Sanquin Bloedvoorziening-Sanquin (The Netherlands)

Supervisors Prof Jan Voorberg

Email address for the applications j.voorberg@sanquin.nl

Subject area: Targeting technology and basic immunology

Project-specific selection criteria: Strong knowledge in nanomedicine-based targeting technologies and basic immunology. Hands-on experience in bioconjugation techniques, nanoparticle and compound synthesis. Experience in immunological techniques is a plus. Excellent team spirit, communication and strong organizational skills, flexibility and creativity

Introduction: Liver sinusoidal endothelial cells (LSEC) have the potential to regulate CD4+ and CD8+ T cell responses. LSECs can be targeted by intravenous injection of specialized peptide-coupled nanoparticles and other bio carriers. After uptake by LSECs, the peptides are released from the nanoparticles and bio carriers and presented by MHCII, resulting in peptide-specific tolerization of CD4+ T cells. Based on proofs of concept of tolerance induction in preclinical T cell- and antibody-mediated diseases we aim to develop in close collaboration with our industry partner Topas developed tolerizing particles (TP) to which various disease-relevant antigenic peptides can be coupled (TPC), that foster antigen-specific tolerance. In parallel we will explore bio-conjugated peptides linked to other tolerogenic with the ultimate goal of restoring tolerance in haemophilia A

Patients with anti-drug antibodies.

Aims: The general objective of this project is to develop nanoparticle-based approach to induce preventive or therapeutic antigen-specific tolerance to therapeutic FVIII. ESR7 will chemically couple immunogenic FVIII peptides to nanoparticles and other tolerogenic carriers. ESR7 will characterize these tolerogenic particles by multiple analytical methods.. ESR7 will perform in vitro tests to analyse the presentation of the released peptide(s) after nanoparticle uptake by APCs and the subsequent stimulation of T cells. ESR7 will be involved in establishing an in vitro assay able to predict the regulatory effect of peptide-coupled tolerogenic carriers. ESR7 will then test the tolerogenic effect of peptide-coupled carriers in pre-clinical models of severe HA. ESR7 will validate the targeting of LSECs and other tolerogenic cells by FVIII-peptide –containing biocarriersusing classical in vivo imaging approaches. ESR7 will then investigate the in vivo tolerogenic effect of FVIII-peptide coupled carriers with Partner B1 and with Partner B4 in relevant animal models.

Expected Results: The results will validate the hypotheses i) that the generation of antidrug antibodies that develop in preclinical models of HA in response to the intravenous injection of therapeutic FVIII can be prevented upon intravenous injection of selected FVIII-peptides coupled to tolerogenic carriers, and ii) that ongoing anti-FVIII immune response may be abrogated using FVIII-peptides coupled to nanoparticles or other tolerogenic carriers.

Planned secondment: ESR7 will be seconded at partner B1 for 5 months from M29 (INSERM, FVIII-KO mice) under the supervision of Dr Sébastien Lacroix-Desmazes. Secondments will have the following objectives: i) injection of FVIII-peptide conjugates to relevant animal models and validation of tolerance induction to therapeutic FVIII by ii) analysis of the antidrug antibody levels in plasma iii) functional coagulation assays iv) immunological studies including T and B cell phenotyping and functional assays

Enrolment in Doctoral degree(s): ESR7 will be registered at (P7 and P9) at Graduate School of the AMC (P7) at the University of Amsterdam (P9), The Netherlands

Project-specific selection criteria: Strong knowledge in nanotechnology and basic immunology. Hands-on experience in bioconjugation techniques, compound design, nanoparticle synthesis and characterization. Experience in immunological techniques is a plus. Excellent team spirit, communication and strong organizational skills, flexibility and creativity.

Recommended reading: [1] Horst AK et al. 2016. Cellular & Molecular Immunology 13, 1–16. [2] Carambia et al. 2015. Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice. J Hepatology 62: 1349-1356. [3] Bargheer et al. 2015. The distribution and degradation of radiolabeled superparamagnetic iron oxide nanoparticles and quantum dots in mice. Beilstein J Nanotechnol 6:111-123. [4] Scott DW et al. 2019. Factor VIII: Perspectives on Immunogenicity and Tolerogenic Strategies. Frontiers in immunology 10: 3078.

 

More Information

Benefits

ESR will be given an employment contract for 48 months by the host institution (33-month period will be covered by EC grant, the remaining period  will be paid with external funds sources)  ESR will be entitled to full employee benefits and inclusion in social security schemes of the host nation. ESR will be compensated according to the general conditions of the EC MSCA and specifically those conditions relating to ESR participating in ITN.

 

Eligibility criteria

Experience eligibility requirement:

Eligible applicants must:

  • hold a Master’s degree or equivalent in a field of science relevant to their chosen project
  • demonstrate a history of academic excellence
  • demonstrate an affinity for Immunology and Molecular Biology
  • speak and write fluently in English
  • have less than 4 years’ previous research experience and not hold a doctoral (PhD) title

Mobility eligibility requirement: The fellow must not have resided in the country where the research training activities will take place for more than 12 months in the 3 years immediately prior to the recruitment date (and not have carried out their main activity (work, studies, etc.) in that country).

Other requirements:

  • In addition to basic and practical knowledge in immunology, the fellows must demonstrate team spirit, sense of commitment, creativity and passion, and excellent communication skills in English (both written and verbal)
  • Despite all European and Third Countries are eligible to apply for this position, we require only the application from EU countries due to VISA issues related to the nature of hosting institution.

Selection process

EDUC8 will select ESR through a 2-step recruitment process.

Candidates should submit their application for their top two preferred research projects. Applications (in English) should include:

1) an updated CV

2) a letter of motivation for the position;

3) at least 1 reference letter (in English) from one former supervisor

4) the scan of the degree (usually the Master Degree) which would formally entitle him/her to embark on a doctorate

5) transcripts of records

The closing date for applications is 16th April 2021. Application documents should be sent by email to the relevant project supervisor( j.voorberg@sanquin.nl)

The candidates will be evaluated on the basis of the received documents and the best 8 candidates will be invited for a Skype interview and ranked.

The 2 top candidates will be invited for a second virtual interview and the final decision will be communicated shortly.

The selected candidate should be available to start his/her project no later than 1st June 2021

Offer Requirements

Skills/Qualifications

A master degree Biomedical Sciences or related.

We are looking for a candidate with a strong background in Molecular and Cellular Immunology, well-developed analytical and technical skills in English (both written and verbal) , a creative thinker, a team-player with excellent communication skills. We offer a highly innovative, stimulatory research environment with an excellent research-infrastructure in a highly ambitious team composed of international researchers.

 

 

Specific Requirements

Strong knowledge in nanotechnology and basic immunology. Hands-on experience in bioconjugation techniques, compound design, nanoparticle synthesis and characterization. Experience in immunological techniques is a plus. Excellent team spirit, communication and strong organizational skills, flexibility and creativity.

Map Information

Job Work Location Personal Assistance locations
Work location(s)
1 position(s) available at
Stichting Sanquin Bloedvoorziening-Sanquin
Netherlands
Netherlands
Amsterdam
1006 AN
Plesmanlaan 125,

EURAXESS offer ID: 619951

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