Research Field: Physics
Researcher Profile: First Stage Researcher (R1)
Application Deadline: 30/09/2022 23:59 - Europe/Brussels
Location: France › STRASBOURG
Type Of Contract: Temporary
Job Status: Full-time
Hours Per Week: 35
Offer Starting Date: 01/04/2023
- In vitro and in vivo analyses of an immune response in cellular and animal
tumor models treated by different schemes of dual therapy including proton
radiations and oncolytic virus infections.
- Exchange, share with and present on the occasion of joint meetings or
conferences your results, to the German group and the scientific society.
- (Co)writting papers presenting results of in vitro and in vivo activation
of an anticancer immune response by dual or triple-agent therapies including
proton radiations and/or oncolytic virus infections.
In the context of DRHIM (Department of Radiobiology, Hadrontherapy and
Molecular Imaging) the post-doctoral fellow will contribute to the
development and building up of a new research project. The project consists in
the pre-clinical characterization of the immunostimulatory and oncosuppressive
activities triggered by combinatorial treatments involving proton irradiation
schemes and infections with oncolytic viruses. The aim is to identify and
develop innovative treatments against brain and pancreatic tumours.
For this purpose, the post-doctoral fellow will evaluate on human and rodent
brain (glioblastoma; GBM) and pancreatic (pancreatic ductal adenocarcinoma;
PDAC) tumor models (cell cultures, syngeneic animal models and human
biopsies), the ability of innovative dual and/or triple-agent combinations,
to stimulate, in vitro and in vivo, an innate and an adaptive immune response
significantly exceeding those potentially triggered by each single agent.
Combinatorial treatments consist in specific proton beam irradiation protocols
(fractionated, hypo-fractionated, or single irradiation) delivered by the
Cyrcé plateform using the Cyclotron Cyrcé located in the department and in
oncolytic virus (OV) infections using wild-type or mutant viruses, including
parvoviruses (PV) MVMp and H-1PV as well as vaccine strain-derived Measles
viruses (MeV), belonging to the BSL2 microorganism family. The position is
part of an ANR PRCI project (Protovec) funded in 2021 involving two research
groups. The first one, led by Dr. Laurent Daeffler, comprises several members
of the DRHIM at IPHC in Strasbourg. The second group is constituted by members
of the national center for tumor diseases (NCT) located in Heidelberg,
Germany, and led by Dr. Guy Ungerechts, Deputy Director of the Medical
Oncology Department at the NCT Heidelberg and head of the Clinical Cooperation
Unit Virotherapy at DKFZ (German cancer research center).
The main in vitro objectives of the project consist in assessing the ability
of the previously mentioned dual or triple-agent combinations to stimulate the
OV life cycle in treated GBM and PDAC cells, spheroids and patient explants,
and concomitantly to synergize in modulating positively or negatively the
innate immune machinery (e.g. cGAS-Sting and RIG-I pathways). This will be
performed among others by assessing the capacity of these treatments to induce
or prevent a type-I interferon (IFN) and ensuing ISGs expression as well as
to sustain, or at least not to prevent, virus replication and multiplication
in human an rodent tumor models compared to single virus infections only
(controls). In vivo, the main objectives will consist in assessing their
ability to eradicate orthotopic (GBM; GL261) and ectopic (PDAC xenografts)
implanted mouse syngeneic tumors in immunocompetent mice (C57BL/6 mice), and
to induce a memory anticancer immune response by attraction of immune cells in
the tumor microenvironment.
The IPHC, a joint research unit under the co-supervision of CNRS and
Strasbourg University (UMR7178), is a pluridisciplinary laboratory where
research groups from various scientific fields (ecology, physiology and
ethology, chemistry and subatomic physics) develop high level research
program with a strong instrumentation basement. IPHC is composed of 4
departments and counts a total number of 393 agents including 257 permanent
position (119 researchers, assistant professors and professors and 138
engineers and technicians), 46 fixed term contracts.
The Institut Pluridisciplinaire Hubert Curien (IPHC) at Strasbourg is
opening a 24-month postdoctoral position in Biology/Immunology/Virology
focused on the search for innovative and alternative therapies against brain
and pancreatic cancers. This research activity will be carried out in the
frame of an ANR PRCI project termed Protovec.
The appealing new project developed at DRHIM is aiming at identifying new
therapeutic protocols able to achieve a decisive break through in the
treatment of extremely aggressive cancers, namely GBM and PDAC that are so far
resistant to all known anticancer therapies. Thereby, patients diagnosed for
these diseases are still today left with a poor prognosis. The group focuses
its research on the combination of radiotherapy protocols and oncolytic virus
infections to achieve this aim since several results andsuggest that these
therapeutic options could synergies in evoking a most effective anticancer
response at least in both latter tumor models. Altogether, the Protovec
program is centered on the identification of treatment combination that could
trigger a most efficient anticancer immune response thus allowing the
development of alternative and innovative immunotherapeutic protocols for the
cure of cancers.
The National Center for Tumor Diseases (NCT) in Heidelberg was founded in
2004 as an exceptional alliance between the German Cancer Research Center
(DKFZ), Heidelberg University Hospital, the Heidelberg Medical Faculty, and
German Cancer Aid (Deutsche Krebshilfe).
The DRHIM department is composed of 6 permanent scientists, (Researchers,
Professors and Assistant professors), 2 PhD students, 1 post-doc and many
engineers and technicians.
The group participating to the Protovec project at DRHIM is composed of 4
permanent researchers, 2 engineers, 2 technicians and is supported
experimentally by the Cyrcé plate-form hosting among others a 24 Mev
cyclotron, an animal facility (BSL2), an irradiation line (PRECy) and a
biological plate-form for cell culture and molecular biology (BSL2).
- Good knowledge in virology and antiviral innate immune mechanisms.
- Good knowledge in molecular and cellular biology.
- Good knowledge in cell culture, qPCR and RT-qPCR, Western blotting, ELISA
and Immunofluorescence experiments.
- Good experience in handling and working with infectious viruses as well as
in BSL2 working conditions and safety.
- Experience in handling and working with laboratory animals (mice)
following the European and French guidelines for laboratory animal care and
- Team working ability, open-minded, working precisely and with
- Level of English at least B2 according to the Common European Framework of
Reference for Languages.
Web site for additional job details
https: // emploi.cnrs.fr/Offres/CDD/UMR7178-REGSOM-125/Default.aspx
Required Research Experiences
YEARS OF RESEARCH EXPERIENCE
REQUIRED EDUCATION LEVEL
Physics: PhD or equivalent
Department: Institut Pluridisciplinaire Hubert Curien
Organisation Type: Public Research Institution
Website: https:// www. iphc.cnrs.fr