REJOIGNEZ LE CRCT

­­Assistant(e) Ingénieur(e) en expérimentation et instrumentation biologiques

Equipe RADOPT – Elisabeth Cohen Jonathan Moyal, CRCT)

Mission et activités principales

La personne recrutée rejoindra le projet «MSrGB: Metabolic Shift in radioresistance of GlioBlastoma» qui concerne l’étude de l’implication d’un shift métabolique dans la radiorésistance des cellules souches de glioblastome. Ce projet intègre une validation in vitro sur des lignées primaires et des échantillons sanguins avec l’imagerie métabolique de patients traités pour un glioblastome en primo-diagnostic

La personne en charge de ce poste aura à réaliser, à partir de protocoles préalablement définis ou à mettre au point, des expériences qui regroupent toutes les techniques de biologie cellulaire, biochimie et biologie moléculaire utilisées dans le laboratoire. Ces différentes techniques pourront être utilisées sur des lignées cellulaires et des échantillons sanguins de patients. L’A.I. recruté.e travaillera au sein d’une équipe de 4 personnes sous la supervision directe d’une enseignant-chercheur et d’un doctorant.

Activités associées :

• Participer à la gestion des stocks et à la logistique du laboratoire
• Former, initier ou aider d’autres membres de l’équipe aux techniques utilisées

Postuler :

Consulter le profil de poste complet

• CDD de 24 mois Temps plein
• Date limite de candidature : 20 février 2023 (prise de fonction Mai 2023)

Envoyer CV , 1 lettre de motivation et 1 lettre de recommandation à anthony.lemarie@inserm.fr

­­Junior Post-Doctoral Position

Equipe MICROPANC – Corinne Bousquet, CRCT)

Research Project / Missions / Scientific context

A postdoctoral research fellow position is available for 3-years at CRCT (Toulouse Cancer Research Center) in Corinne Bousquet’s Research group « Microenvironment & Therapeutic Resistance in Pancreatic Neoplasms. »
The project aims at understanding pancreatic cancer heterogeneity in spatial cell positioning, focusing on the interplay between cancer cells, cancer-associated fibroblasts and immune cells, to understand immune cell exclusion within sub-tumor microenvironment areas. Within an European Consortium (Belgium, Spain, Italy & France), the role of specific guidance cues that may organize cell attraction or repulsion will be explored. To do so, multiplex RNA and protein immunohistofluorescence on pancreatic cancer tissue shall be developed, as well as functional assays using 3D cell co-cultures.
Toulouse is a dynamic research area located in south of France that comprises many internationally recognized laboratories (fundamental cell biology, pharmacology, cancerology, immunology, metabolism, agronomy…) and gives access to a network of high-level skills research platforms in life sciences (GENOTOUL – Un ensemble de ressources au service de la R&D, e.g. imaging, cytometry, bioinformatics, genomics & transcriptomics, biostatistics ; Metatoul – Home (inrae.fr), e.g. metabolomics & fluxomics; Toulouse Proteomics Infrastructure | IPBS, e.g. proteomics) making possible almost all research projects.
The Toulouse Cancer Research Center, accredited by INSERM, CNRS and Toulouse University, is internationally recognized and offers a productive scientific environment centered on basic, transdisciplinary (bioinformatics, mathematics & physics in close link with the Toulouse Laboratoire d’analyse et d’architecture des systèmes | LAAS-CNRS and Laboratoire de Physique et Chimie des Nano-objets (insa-toulouse.fr)), and clinical research (in close link with the IUCT Oncopole – Institut Universitaire du Cancer de Toulouse – Accueil (iuct-oncopole.fr)), to understand and treat cancers. CRCT brings together a total of >250 Researchers, MDs, University Professors, Technicians, Students and Post-docs of many nationalities. CRCT offers on-site state-of-the-art technological platforms with personalized project support, including single cell RNAseq (Le pôle technologique DU CRCT – Centre de Recherches en Cancérologie de Toulouse (crct-inserm.fr)).

Main missions :

• Multiplex imaging (RNAs & Proteins) and image analyses on pancreatic cancer tissues
• Set up of 3D co-cultures of patient-derived cancer-associated fibroblasts with cancer cells and immune cells
• Functional characterization of selected guidance cues using molecularly engineered 2D and 3D patient-derived cell models, and in vivo murine models of pancreatic cancer (orthotopically grafted with cancer cells).
• Experimental design & organization, Statistical analysis, Result interpretation & reporting (oral in english during Labmeetings; written for grant reporting & application, and manuscript preparation)
• Involvement in the tutoring of 1 to 2 Master/ PhD Students
• Strong interaction with other Lab members (help with experiment design, interpretation,…)

Contract :

• Type : CDD
• Length  : 36 months
• Salary : 2.856,02€ gross monthly depending on experience post-PhD.Salary will follow INSERM guidelines commensurate with training and experience
• Starting date Position  : starting in April 1rst, 2023, the latest

To Apply :

Please send a motivation letter explaining your interest in this job advertisement, CV and the names of three references to: corinne.bousquet@inserm.fr

Consulter le profil de poste complet(en anglais)

­­Assistant-e Ingénieur-e Expérimentations Biologiques

Equipe MICROPANC – Corinne Bousquet, CRCT)

Mission principale

Sous la direction scientifique du Dr Corinne BOUSQUET (DR2 INSERM U1037) : Développer des modèles cellulaires de cancer pancréatique, à partir desquels le dialogue entre cellules tumorales et du microenvironnement tumoral pourront être identifiés. Assurer la gestion de ces modèles et leur caractérisation fonctionnelle pour l’équipe. Etre responsable de tâches transversales au sein de l’équipe (immuno-pathologie, biologie moléculaire et biochimie, assistante à l’expérimentation sur petits modèles animaux).

Conditions du poste :

• CDD de 12 mois renouvelable
• Prise de fonction : 1er trimestre 2023
• Date limite de candidature : 22 janvier 2023

Candidature :

Envoyer CV et lettre de motivation par mail à Corinne Bousquet

Consulter le profil de poste complet

­­Post-doc Position in 2023: Targeting pre-leukemic stem cells in B-cell acute lymphoblastic leukemia

(Bastien GERBY, Cancer Research Center of Toulouse, France)

General problematic: The cell of origin of B-ALL

B-cell acute lymphoblastic leukemia (B-ALL) is a multi-step disease characterized by the acquisition of a first oncogenic event such as ETV6::RUNX1, BCR::ABL1 or TCF3::PBX1 fusion genes or specific PAX5 alterations (such as PAX5::ELN or P80R point mutation). Genome-wide analyses have been used to draw the genomic landscape and the gene expression profile of B-ALL patients leading to patient stratification and the discovery of new therapeutic opportunities. However, although chemotherapies are efficient at reducing the tumor load by targeting proliferating and metabolically active leukemic cells, the disease relapse, especially in adult B-ALL, points to the presence of resistant cells that escape treatment. Thus, the biological properties of the cell-of-origin of leukemia, including oncogene-induced reprogramming, cell plasticity, sustained self-renewal activity, cell-quiescence and drug-resistance, can affect the treatment and should be considered in the search for new targeted therapies (Fregona V et al., Cancers (Basel) Review, 2021).

Research Context: A unique murine model of B-ALL

In this context, our research focuses on the characterization and the targeting of pre-leukemic stem cells (pre-LSCs) in B-ALL. We develop cellular and animal models aiming to understand how a primary oncogene in B-ALL such as a chromosomal translocation, reprograms normal B-cells to pre-LSCs as demonstrated in our 2018 PNAS paper. Indeed, we generated the PAX5::ELN transgenic mouse model that recapitulates the multi-step process of B-ALL and that represents a prime tool to explore the pre-leukemic phase of the disease before the overt transformation (Jamrog L et al., PNAS, 2018). Our recent work indicates that pre-LSCs: (i) are restricted in the cell-cycle, (ii) are devoid of secondary mutations, (iii) are blocked in the B-cell differentiation, (iv) are resistant to chemotherapeutic agents, (v) up-regulate a stem cell-like molecular programs and (vi) sustain the leukemia initiation and transformation. Thus, our work indicates that PAX5::ELN reprograms stem cell-like properties in a subset of B-cell progenitors and converts them into quiescent pre-LSCs (Fregona V et al., submitted).

Proposed project: Targeting leukemia initiating activity

We recently designed a robust protocol for the screening of compounds targeting primary pre-LSC-enriched population. We screened a bank of 1040 natural and synthetic compounds and identified drug candidates that affect their viability. Using further investigations (counter screens on quiescent cells, dose-responses, synthetic lethality assays, RNA-sequencing, transplantation assays), the post-doc candidate will have in charge to identify the most relevant compound that affects the cell-quiescence/resistance, the self-renewal potential and the gene expression profile of PAX5-ELN pre-LSCs. In addition, the candidate will define whether targeting pre-LSC biological properties is relevant in other B-ALL models available in the lab (PAX5-P80R and TCF3::PBX1 mouse models or human B-ALL patient-derived-xenografts (PDXs)).

Candidate profile and application

We are seeking a dynamic and proactive post doc. The candidate should have good experience in mouse models, flow cytometry, as well as in culture of primary cells. Skills in hematopoiesis and in bioinformatics would be very welcome. With our strong help and support, the selected candidate will have to apply in 2023 for a Postdoctoral Fellowship from different institutions (Fondation ARC, Fondation pour la Recherche Médicale, Fondation de France,…). The applicant is invited to send a CV with list of publications, research experiences and referees to Bastien Gerby (bastien.gerby@inserm.fr).

Situation & scientific environment

Our team “Impact of genetic alterations on leukemia development” led by Pr. Eric Delabesse is located at the Cancer Research Center of Toulouse (CRCT, UMR1037, CNRS UMR5071). The team is composed of 16 people including two PU-PH, three researchers, four engineers, two technicians and five students at the MSc and PhD levels. The laboratory promotes multidisciplinary approaches allowing an efficient investigation and deeper understanding of normal and aberrant hematopoiesis. Combined with clinical studies and genetic profiling of leukemia patients, the development in our team of cellular and animal models aims to define and target the biological mechanisms by which genetic alterations lead to leukemia development. The projects are supported by grants from INCa, ANR, ARC Foundation, Ligue Contre le Cancer and from the associations “Laurette Fugain”, “111 des arts”, “Cassandra” and “Constance la petite guerrière astronaute”.

As a post-doc, you will have a full access to facilities available in the CRCT (https://www.crct-inserm.fr/en/the-technology-cluster-of-the-crct/) including flow cytometry/cell sorting, bioinformatics, vectorology and genomics platforms.

Webpages of the team:

https://www.crct-inserm.fr/en/characterization-and-targeting-of-pre-leukemic-stem-cells-from-b-acute-lymphoblastic-leukemia/
https://www.crct-inserm.fr/en/igaald_en/
https://www.crct-inserm.fr/en/axis-1-oncogenic-pathways-in-cancer-from-modelization-towards-targeted-therapy/ 

Contacts:

Project leader: Dr. Bastien Gerby: bastien.gerby@inserm.fr Team leader: Pr. Eric Delabesse: delabesse.e@chu-toulouse.fr

Selected references:

• Fregona V et al. Cell quiescence and reprogramming are distinctive features of pre-leukemic stem cells in B-cell acute lymphoblastic leukemia. Submitted.
• Fregona V et al. Oncogene-Induced Reprogramming in Acute Lymphoblastic Leukemia: Towards Targeted Therapy of Leukemia Initiating Cells. Cancers (Basel) Review, 2021 Nov 2, 13(21):5511.
• Duployez N et al. Germline PAX5 mutation predisposes to familial B acute lymphoblastic leukemia. Blood, 2021 Mar 11;137(10):1424-1428.
• Jamrog L et al. PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice. Proc Natl Acad Sci USA. 2018 Oct 9;115(41):10357-62.
• Cresson C et al. PAX5A and PAX5B isoforms are both efficient to drive B-cell differentiation. Oncotarget. 2018 Aug 28;9(67):32841-54.
• Gerby B et al. High-throughput screening in niche-based assay identifies compounds to target pre-leukemic stem cells. J Clin Invest. 2016 Dec 1;126(12):4569-84.
• Gerby B et al. The SCL, LMO1 and Notch1 oncogenes reprogram T-lymphocyte progenitors into self-renewing cells. PloS Genetics. 2014 Dec 18;10(12).

­­Postdoctoral position (M/F; 1 yr, renewal 3 yrs)​

PROJECT

IRONAML53 – Uncovering and targeting metabolic vulnerabilities of acute myeloid leukemia harboring TP53 mutations, promoting Darwinian advantages in leukemic evolution and drug resistance

The postdoctoral fellow will be implicated in a highly collaborative project between the CRCT (JE Sarry,Toulouse), METATOUL (JC Portais, Toulouse), IRCM (L Le Cam, Montpellier) and Cochin (C Peysonneaux, Paris). The postdoctoral fellow will establish unique PDX models (well handled by the
CRCT) and novel GEMMs and will study cellular and metabolic mapping of TP53 mutant leukemic blasts and their microenvironment in those models. He/she will be devoted to unravel the role of host iron in the development of selective advantage and chemoresistance of distinct TP53 clones. Her/his work will be done in close collaboration with PhD students and engineers working on the multidisicplianry project. General responsibilities include design, implement and interpret experiments, both independently and in collaboration, and communicate research and findings in a clear and concise
manner. The postdoctoral fellow will present the progress of the project during bi-monthly meetings between the different teams, as well as during national and international conferences.

EMPLOYMENT

Starting beginning of 2023, the job position is funded by an INCA-HRHG grant.
The application should be written in English and include:
1. Letter of motivation with a short description of the applicant’s previous research and why
the applicant considers her/himself a good match for the position (1-2 pages).
2. Curriculum vitae, including a description of relevant skills and experiences, as well as a full
publication list.
3. Names, e-mail addresses and telephone numbers to 2-3 references.

CONTACT

Application should be sent to Jean-Emmanuel Sarry (jean-emmanuel.sarry@inserm.fr).

More information >>>

­­Décrypter la complexité des cancers du sein agressif pour améliorer leur survie

Le Centre de Recherches en Cancérologie de Toulouse (CRCT, Inserm / CNRS / Université Toulouse III Paul Sabatier), conjointement avec la Fondation Toulouse Cancer Santé et l’Institut Claudius Regaud (Centre de Lutte Contre le Cancer), lancent un appel à projets pour recruter une équipe de recherche travaillant dans le domaine du cancer du sein triple négatif (TNBC, Triple Negative Breast Cancer).

Le cancer du sein triple négatif (TNBC) est un néoplasme très hétérogène et cliniquement agressif qui représente 15 à 20 % des cancers du sein avec le taux de mortalité le plus élevé de tous les sous-types de cancer du sein.

Le TNBC est défini par un état peu différencié, l’absence d’expression du récepteur d’œstrogène (ER) ou du récepteur de progestérone (PR), et sans surexpression/amplification du HER2 humain. Contrairement au cancer du sein à récepteurs hormonaux positifs, qui est généralement traité par hormonothérapie, ou au cancer du sein HER2 positif, qui peut être traité par des anticorps thérapeutiques (par exemple, le trastuzumab), la gestion du TNBC ne bénéficie pas jusqu’à présent d’une thérapie ciblée efficace, et la chimiothérapie conventionnelle reste la norme de soins pour les patients, avec un impact clinique limité. En outre, la biologie moléculaire de ce type de cancer est encore mal comprise. Par conséquent, une meilleure connaissance de l’oncogenèse et l’identification de nouvelles cibles thérapeutiques pourrait grandement bénéficier aux patients atteints de TNBC.

L’objectif de cette chaire est de mieux comprendre la génétique, la biologie et le microenvironnement du TNBC, en se basant sur des technologies innovantes telles que l’analyse moléculaire de cellules uniques, comme source de nouvelles cibles et de stratégies thérapeutiques.

Cette chaire s’adresse à des chercheuses et chercheurs de classe mondiale. La lauréate ou le lauréat bénéficiera d’un financement correspondant à un équivalent ERC Starting, soit 1,5 millions d’euros pour une durée de 5 ans. Les modalités du financement seront négociées avec la lauréate ou le lauréat.

Cette chaire s’inscrit dans les priorités scientifiques du CRCT et bénéficiera du soutien des équipes cliniques et biocliniques de l’IUCT-Oncopole qui étudient actuellement le paysage génomique et les caractéristiques du TNBC métastatique. La lauréate ou le lauréat mènera des recherches de niveau international en utilisant des plateformes technologiques de pointe, partagée entre le CRCT et l’IUCT-Oncopole, pour l’exploration moléculaire des tissus des patients.

Les candidatures doivent impérativement comprendre :

• Un résumé du projet, non confidentiel et grand public (1 page maximum, police Calibri 10)
• Le projet scientifique complet, incluant les objectifs scientifiques du projet, la méthodologie et les techniques, ainsi que les résultats attendus (5 pages maximum hors figures, police Calibri 10).
• Le CV complet de la candidate ou du candidat.
• La liste complète des publications de la candidate ou du candidat.
• Une proposition de budget prévisionnel

L’évaluation des projets sera faite sur site par un jury externe international au printemps 2023, avec une prise de poste attendue à l’automne 2023. Le calendrier exact sera précisé ultérieurement aux candidats.

Les candidatures sont à transmettre avant le 31 mars 2023 à sebastien.guibert@inserm.fr