28/10/2021
Marie Skłodowska-Curie Actions

EDUC8: Call for applications from Early Stage Researchers for 8 Doctoral (PhD) Training Positions in basic and translational immunology. High-throughput B-cell epitopes profiling


  • ORGANISATION/COMPANY
    INSERM 1138
  • RESEARCH FIELD
    Biological sciencesOther
  • RESEARCHER PROFILE
    First Stage Researcher (R1)
  • APPLICATION DEADLINE
    10/12/2021 23:00 - Europe/Brussels
  • LOCATION
    Italy › Milan
  • TYPE OF CONTRACT
    Temporary
  • JOB STATUS
    Full-time
  • HOURS PER WEEK
    40
  • OFFER STARTING DATE
    01/02/2022
  • 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, for Molecular Biology and for statistics and bioinformatics
  • 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 Italy 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 February 2022

Individual Projects details

ESR3: High-throughput B-cell epitopes profiling

Hosting Institution: University of Milan (Italy)

Supervisor Prof Flora Peyvandi and Roberta Palla

Email address for the applications flora.peyvandi@unimi.it; roberta.palla@unimi.it

Subject area: Bioinformatic applied to immunology

Project-specific selection criteria: • A master degree in Biomedical Sciences or related, with strong knowledge in Biology and Immunology, and experience in common techniques in Molecular Biology

• Background in statistics and good programming skills (R or Python).

• Good knowledge of Linux/Unix system.

• Preferred experience with the analysis of NGS data (e.g. RNA-seq, WES, WGS).

• Good problem-solving skills, strong attitude to develop novel analytical pipeline.

• Constructive attitude with the supervisor and the team, communication and strong organizational skills, flexibility and creativity.

Introduction: The anti-FVIII immune response is characterized by the production of polyclonal IgG directed against multiple epitopes located on the A2, A3-C1 and C2 domains of FVIII. UMIL documented that pre-existing anti-FVIII antibodies are an important risk factor for the development of FVIII inhibitors. A controversy has prevailed over the last two decades on the higher immunogenicity of therapeutic recombinant FVIII (rFVIII) as compared to plasma-derived FVIII (pdFVIII). The prospective randomized SIPPET study, substantiated by a recent observational open cohort, has shown that rFVIII concentrates are indeed associated with an 87% higher incidence of inhibitor development than pdFVIII products. Nonetheless, some cohort studies report contradictory results and the mechanisms underlying the higher immunogenicity of rFVIII over pdFVIII remain unknown. This task will investigate differences in epitope profiles between patients who have developed FVIII inhibitors under pdFVIII or rFVIII. Our preliminary data reveal distinct immuno-profiles in plasma obtained pre- and post-treatment from patients with or without inhibitors

Aims: ESR3 will exploit a high-throughput random peptide screening strategy (Mimotope Variation Analysis – MVA, developed by PROTOBIOS), which combines peptide display library and next-generation DNA sequencing. Using the MVA technique, ESR3 will compare the arrays of B-cell epitopes recognised by antibodies from HA patients before and after treatment with therapeutic FVIII, as function of their inhibitory status. ESR3 will also compare the arrays of B-cell epitopes recognised by antibodies from inhibitor-positive HA patients treated with plasma-derived or recombinant FVIII products. ESR3 will develop ELISA and exploit the SIPPET cohort to evaluate the predictive value on the development of FVIII inhibitors of the recognition of particular sets of peptides by antibodies in the plasma of naïve patients

Expected Results: The project will allow a fine mapping of the existing FVIII epitopes previously identified as targets for anti-FVIII alloantibodies as well as identification of new FVIII epitopes. It will highlight, for the first time, the differences in humoral responses to rFVIII and pdFVIII products. It will also provide the first detailed comparison of the base-line differences in IgG reactivities between patients that will or will not develop FVIII inhibitors, prior to exposure to FVIII. Interestingly, the results will identify immunogens other than FVIII that predispose patients to inhibitor development. Last, the project shall lead to the development of an ELISA kit to predict the development of FVIII inhibitor in naïve HA patients

Planned secondment: ESR3 will be allocated to P2 PB under the supervision of Prof Sergio Abrignani at Month 10 for 10 months to be trained on bioinformatics analysis of data and on RNA-seq and epitope mapping

Enrolment in Doctoral degree(s): ESR3 will be enrolled at the Doctoral School in Medicina Traslazionale (Translational Medicine) in the Department of Pathophysiology and Transplantation of the University of Milan.

Project-specific selection criteria:

• A master degree in Biomedical Sciences or related, with strong knowledge in biology and Immunology, and experience in common techniques in Molecular Biology

• Background in statistics and good programming skills (R or Python).

• Good knowledge of Linux/Unix system.

• Preferred experience with the analysis of NGS data (e.g. RNA-seq, WES, WGS).

• Good problem-solving skills, strong attitude to develop novel analytical pipeline.

• Constructive attitude with the supervisor and the team, communication and strong organizational skills, flexibility and creativity.

 

 

More Information

Benefits

ESR will be given an employment contract for 36 months by their host institution (24-month period will be covered by EC grant, the last 12 months 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, Molecular Biology and bioinformatics
  • 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, molecular biology and bioinformatics, 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 30 November 2021. Application documents should be sent by email to the relevant project supervisor flora.peyvandi@unimi.it and cc to roberta.palla@unimi.it

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 February 2022

Offer Requirements

Skills/Qualifications

A master degree Biomedical Sciences or related.

We are looking for a candidate with a background in Molecular biology and Immunology and basic information in bioinformatics, 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

Background in statistics and good programming skills (R or Python).

• Good knowledge of Linux/Unix system.

• Preferred experience with the analysis of NGS data (e.g. RNA-seq, WES, WGS).

• Good problem-solving skills, strong attitude to develop novel analytical pipeline.

• Constructive attitude with the supervisor and the team, communication and strong organizational skills, flexibility and creativity.

Map Information

Job Work Location Personal Assistance locations
Work location(s)
1 position(s) available at
University of Milan (Italy) UMIL
Italy
Milan

EURAXESS offer ID: 702381

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