Igg4-Treat R10: Development Of A Novel Igg4-Specific Immunoadsorption Therapy For Commercial Exploitation (Msca Doctoral Network)

27 Oct 2023

Job Information

Organisation/Company

IgG4-TREAT (Tzartos Neurodianostics, Hellenic Pasteur Institute, National & Kapodistrian University of Athens)

Research Field

Biological sciences

Medical sciences

Researcher Profile

First Stage Researcher (R1)

Country

Greece

Application Deadline

31 Jan 2024 - 23:59 (Europe/Vienna)

Type of Contract

Temporary

Job Status

Full-time

Hours Per Week

40

Is the job funded through the EU Research Framework Programme?

HE / MSCA

Marie Curie Grant Agreement Number

101119457

Is the Job related to staff position within a Research Infrastructure?

No

Offer Description

Short overview of the program:

IgG4-TREAT consortium is l ooking for highly motivated and talented PhD students to contribute to groundbreaking research in the field of IgG4-autoimmune diseases (IgG4-AID). The PhD researchers will have the opportunity to participate in a comprehensive training programme in academic and industry setup. Next to their transferable skills training, the IgG4-TREAT PhD students will pursue 10 individual, multidisciplinary research projects (organised into four scientific work packages) aimed to advance our understanding of IgG4-AID.

PhD candidates will become part of a network of 9 host laboratories and 7 associated partners from 7 different European countries. Funding for these projects has been provided by the EU under the competitive MSCA Doctoral Networks 2022 program (Grant Agreement No. 101119457). For more information on IgG4-TREAT visit our website: https: // www. igg4-treat.eu/.

Project R10: Development of a novel IgG4-specific immunoadsorption therapy for commercial exploitation

Hosting lab + location:

Tzartos NeuroDiagnostics (TND), Athens, Greece. (PI and Co-supervisor: Socrates Tzartos)

Department of Immunology, Hellenic Pasteur Institute (HPI), Athens, Greece. (PI and Co-supervisor: Konstantinos Lazaridis)

Second Neurology Department, University of Athens (NKUA), Athens, Greece. (PI and Co-supervisor: John Tzartos)

Research project description:

Development of a novel IgG4 removal therapy for commercial exploitation

To develop a new approach for specific treatment of all IgG4-mediated autoimmune disease (AID) by removing the IgG4 Abs from the patients' circulation. IgG4-AID disease severity correlates with IgG4 titers, while removal of IgG through plasmapheresis in the majority of IgG4-AID patients results in fast improvement of the patient's symptoms. The Ph.D. student R10 (with the supervision of the three PIs) will develop and optimize the IgG4 removal approach. The various parameters that may affect treatment efficiency will be examined (e.g. efficiency and speed of IgG4 removal etc.), and the therapeutic potency of the method will be assessed. The major advantages of the proposed therapy are that a. it is relatively specific and yet it aims to the whole group of IgG4-diseases, b. it should be feasible and not too expensive because the IgG4 is a small Ig fraction (~1/20 of the whole human Ig) c. Selective IgG4 removal will not significantly deplete the patients from their protective immunoglobulins.

Main objectives :

We will determine the IgG4 removal efficiency, speed and capacity of the system for IgG4 Abs in vitro. Then (during a secondment to the Istanbul University), the approach's therapeutic potential will be assessed in vitro by testing the effect of whole serum or following IgG4 removal in cell cultures by disruption of AChR clustering in C2C12 cells in the case of MuSK Abs, or neuronal toxicity in the case of LGI1 Abs. Additionally, the calcium status of neurons will be assessed by the Ca++-imaging method. We will determine the therapeutic potency in vivo using passive transfer animal models induced by injection of patient sera in rats for MuSK-MG and autoimmune encephalitis (LGI1 and CASPR2 Abs) and by injection of cloned CASPR2 Abs. These will confirm the therapeutic potential of the approach in conditions similar to the clinical setting.

Methods used in the project: Antibody production, Heterologous protein production, Affinity chromatography, Cell-based assays, Radioimmunoassay, Antibody function on cell cultures, Ca++-imaging method, SIMOA (Single molecule array) technology, Induction of experimental IgG4-disease in animal models, Rodent handling and surgical techniques.

In vivo studies in experimental animals are a part of the project. Therefore, the applicant will be required to handle and perform procedures (surgical and other) on experimental animals (small rodents), subject to approval from regulatory bodies.

Project duration: 36 months (40 h/week)

Should extra time be needed, the hosts will try to cover the student expenses for 1-2 years until completion of the study

Hosting labs descriptions:

The PhD candidate will work in 3 intimately collaborating places in Athens: the research and diagnosis laboratory Tzartos NeuroDiagnostics (PI and Co- supervisor: Socrates Tzartos), the Immunology Department of the Hellenic Pasteur Institute (PI and Co-supervisor: Konstantinos Lazaridis) and the 2nd Neurology Department of the School of Medicine, National & Kapodistrian University of Athens, NKUA (PI and Co-supervisor: John Tzartos). The collaborating groups have extensive and documented relevant expertise in the research topic and in PhD supervising.

Tzartos NeuroDiagnostics (TND) is a major private laboratory in Greece specializing in research and diagnosis of neuroimmune diseases, created in 2013. Some of its diagnostics are unique in Europe and it serves several European labs/clinics. It is also very active in research, discovering new antibodies and developing new diagnostics. The personnel of the lab includes 2 MDs, 2 post-docs (biologist and chemist), 2 Ph.D. students, 3 biologists with Masters' degrees and 4 technicians. TND is fully equipped with all needed instrumentation, including a complete cell culture facility, fluorescent microscope, the high-tech SIMOA HD-X instrument, Fluostar Omega, Lumipulse automatic analyzer, recombinant protein production unit with all needed instrumentation radioimmunoassay facilities with multichannel gamma counters, etc. In addition, it has easy access to the instrumentation of nearby research establishments.

The Hellenic Pasteur Institute (HPI) is the oldest biomedical research institute in Greece. It has a well-established expertise in neuroimmune and autoimmune diseases, offering a vibrant research environment supporting young researchers. HPI has core bio-imaging and animal facilities equipped with behavioural and microsurgery units, enabling the execution of advanced studies in animal models. In addition, the host laboratory is fully equipped (e.g. tissue culture, radioactivity work-space, ELISA readers) for the proposed experiments. Konstantinos Lazaridis has expertise in the development of new animal models of autoimmune diseases, in vivo preclinical studies for testing the therapeutic efficacy of novel treatments (including antibody aphaeresis) and in vitro characterization of antibody aphaeresis methods as treatment.

The University of Athens (NKUA) is the oldest and major Greek University. It teaches many disciplines. Its Medical School is also the oldest and major Greek Medical School. Its B' Neurology Department, part of the large University hospital "Attico", serves patients from almost half the Athens/Attica area (~2 million people). It has a strong clinical and research interest in neuroimmune diseases, the main expertise of the PI, including the IgG4-related ones. The contribution of John Tzartos will be mostly on clinical aspects on which the B' Neurology Dep. has extensive expertise and is fully equipped. In addition, laboratory infrastructure and instrumentation are available both at the clinic's laboratory and at the collaborating laboratories of the Atticon Hospital.

Foreseen mobility: Secondment is planned in:

Istanbul University (supervised by V. Yilmaz and E. Tüzün, Turkey): Analyze pathogenicity of depleted sera in primary rat hippocampal neurons.

Requirements

Research Field

Biological sciences

Education Level

Master Degree or equivalent

Research Field

Medical sciences

Education Level

Master Degree or equivalent

Skills/Qualifications

The PhD candidate will be enrolled in the School of Medicine, National & Kapodistrian University of Athens (NKUA). Enrolment requires a Master's degree (students with MD degree do not need Master's).

English language proficiency is required. This may be proved by appropriate degrees, studies in English programmes or during the interviews or a combination of these alternatives.

Languages

ENGLISH

Level

Excellent

Additional Information

Benefits

The funding is guaranteed for 36 months and will include:

a monthly living allowance of 3,400 EUR/month (gross salary will be adjusted through the application of a country correction coefficient for the country in which the researcher is recruited; as indicated in Table 1 of the MSCA Work Programme)

a monthly mobility allowance of 600 EUR/month;

a monthly family allowance (if applicable), of 660 EUR/month.

Allowances are gross amounts , which means that all compulsory social security contributions, direct taxes, and any other compulsory deductions under national legislation will be deducted from these amounts.

Eligibility criteria

Applicants must not have resided or carried out their main activity (work, studies, etc.) in the host country for more than 12 months in the 36 months immediately preceding the starting date of the PhD (earliest starting date: 31/03/2024) ( MSCA Mobility Rule ).

At the time of the deadline, applicants must not be in possession of a doctoral degree or have successfully defended their doctoral thesis awaiting formal notification.

At the time of enrolment, applicants must be eligible for enrolment for PhD studies at the hosting institution.

Selection process

How to apply:

Interested candidates can find more information on the consortium website. Candidates can apply for up to three positions and should indicate their preferences in the application form. To apply, please send the following application documents as a single PDF file to [email protected]. As the subject of your email, please use IgG4-TREAT application-your last name.

Application Form (available for download on the consortium website https: // www. igg4-treat.eu/apply)

CV (in Europass or ORCID format) including any publications, prizes/grants obtained, and international experience. The candidates are asked to highlight any extra-professional activities to measure leadership, creativity, communication abilities, etc. as well as their hobbies.

Motivation letter : 1 page highlighting the main expertise of the applicant, career plans and motivations for the program.

Copy of transcripts and diploma(s) for the obtained degree(s). If the degree is imminent, but not yet obtained, a letter from the University delivering the degree must be included.

Contact details (e-mail address and phone number) to possible referees - direct research supervisor(s) at current (or last) university at the time of enrolment.

Copy of an ID or Passport

All documents need to be provided in English. We aim for a maximum level of inclusiveness in our recruitment, and to reduce the risk of any bias, we ask that candidates focus only on their academic qualifications and make sure that no information on biological sex, gender identity, age, ethnicity, or sexual orientation is included in the application documents (with the exception of the application form).

Recruitment procedure:

The selection procedure will be open, transparent, merit-based, and in line with the Code of Conduct for the Recruitment of Researchers. All the network institutions are equal opportunity employers and seek a workforce diverse in age, culture, nationality and gender.

The application process will start in October 2023. The deadline for applications is 31/01/2024. The individual projects are set to start between 31/03/2024 and 01/09/2024.

The selection process will consist of several steps. First, we will check if the applications are complete and if the applicants fulfill the eligibility criteria. Then, each eligible application will be evaluated by the prospective supervisors, according to project preferences indicated by the applicant. Shortlisted candidates will be invited for the next steps of the application process including several rounds of online interviews with prospective supervisors and other supervisors from the network. Successful candidates will be informed within a few weeks after the interviews.

Website for additional job details

https: // www. igg4-treat.eu/apply/

Work Location(s)

Number of offers available

1

Company/Institute

Immunology Department of the Hellenic Pasteur Institute, Athens, Greece

Country

Greece

City

Athens

Postal Code

115 21

Street

127 Vas. Sofias Av

Number of offers available

1

Company/Institute

Tzartos Neurodiagnostics

Country

Greece

City

Athens

Postal Code

11523

Street

3 Eslin str

Geofield

Number of offers available

1

Company/Institute

2nd Department of Neurology "Attikon" Hospital of the School of Medicine, National & Kapodistrian University of Athens, Greece

Country

Greece

City

Athens

Postal Code

124 62

Street

1 Rimini Str.

Geofield

Where to apply

Website

https: // www. igg4-treat.eu/apply/

Contact

City

Athens

Website

https: // www. igg4-treat.eu/

E-Mail

[email protected]

STATUS: EXPIRED