PhD fellowship at the interface between Cancerology / Immunology / Vascular biology M/F

3 years full time PhD student position funded by LABEX TOUCAN: Laboratoire d’Excellence Toulouse Cancer

starting date: October 1st, 2021

is available in the Teams of Jean-Philippe GIRARD: IPBS, CNRS and University of Toulouse, France and Camille LAURENT: CRCT, Inserm and University of Toulouse

Project Title: SINGLE CELL MAPPING OF THE VASCULATURE IN AGGRESSIVE B LYMPHOMAS AND TOPOLOGICAL INTERACTIONS WITH CD8 T CELLS AND y8 T CELLS

Keywords: aggressive B lymphoma, high endothelial venule, endothelial cell, spatial transcriptomics, scRNA-seq, anti-tumor immunity)

Abstract: Immunity plays an important role in cancer control, notably with highly mutated tumours such as Diffuse Large B-cell Lymphoma (DLBCL), an aggressive (fast-growing) non-Hodgkin lymphoma that affects B cells. Indeed, CD8 T cells and γδ T cells display potent antitumour cytotoxicity and are specifically reactive to lymphomas. DLBCL often develops in the lymph nodes. High endothelial venules (HEVs) are specialized blood vessels for lymphocyte entry into lymph nodes. HEVs may thus play an important role in the recruitment of CD8 T cells and γδ T lymphocytes in DLBCL lymph nodes.

The major objective of the project is to perform single cell mapping and spatial transcriptomics (ST) to characterize the density, maturation and functional status of HEV endothelial cells (MECA-79+CD31+) and non-HEV endothelial cells (MECA-79-CD31+), and define their topological interactions with cytotoxic  γδ T cells and CD8 T cells in DLBCL patient’s biopsies. The project will greatly benefit from the expertise of:
– Jean-Philippe Girard’s team (IPBS) on HEV blood vessels, scRNASeq analyses of endothelial cells, and HEV-mediated lymphocyte recruitment in lymph nodes (Moussion and Girard, Nature 2011; Girard et al., Nat Rev Immunol 2012; Lafouresse et al., Blood 2015; Veerman et al., Cell Rep 2019), and
– Camille Laurent’s team (CRCT) on human B cell lymphomas (Laurent et al., Blood. 2020; Laurent et al., J Clin Oncol. 2017; Laurent et al., Blood. 2011), cytotoxic T cells, single cell RNA sequencing (scRNASeq, CITEseq) (Pizzolato et al., PNAS 2019; Pont et al., Nucleic Acids Res 2019) and spatial transcriptomics (transcriptomic hallmarks of all cells in a lymphoma biopsy in situ).

This study will deeply increase our knowledge about the distribution and functional status of HEV and non-HEV endothelial cells, γδ and other cytolytic T cells infiltrating human lymphomas. It may have important clinical consequences such as the identification of new predictive biomarkers, and guide T cell-based immunotherapies currently developed in Comprehensive Cancer Centers worldwide.

Requirement: Master in Cancerology, Immunology, Vascular Biology or Molecular Biology. Experience in scRNA-seq and/or bioinformatics will be a plus. We are looking for a creative and highly motivated PhD student strongly committed to research. Joint PhD supervisors: Drs Jean-Philippe Girard (IPBS) and Camille Laurent (CRCT).

Contract: 3 years full time PhD student position funded by LABEX TOUCAN (starting date: October 1st, 2021). The salary is in accordance with the French Ministry for Higher Education and Research salary scale. Social security and health benefits are included. Work context: research conducted at both IPBS and CRCT, two large Research Centers from CNRS, Inserm and University of Toulouse. All the necessary biological resources and research facilities, including state of the art technological facilities, will be available.

 

Deadline: the position will remain open until filled; only successful applicant will be contacted

How to apply: Please, send your application (in French or English, including a motivation letter, curriculum vitae, and rankings in University Licence/Master or Engineering school).

Research Scientist position to Study the Role of Metabolic Dialogues in Drug Resistance of Acute Myeloid Leukemia

Postdoc position

RESTORE lab, Toulouse, France
1 year – renewable twice; full time job

TITLE AND OBJECTIVE OF THE PROJECT

«Targeting metabolic dialogue in drug resistance of acute myeloid leukemia»Despite an improvement in the complete response rate obtained after conventional chemotherapy, overall survival of acute myeloid leukemia (AML) patients is still poor due to relapses caused by tumor regrowth initiated bydrug resistant leukemic clones.Theproject aims at elucidating how the metabolic dialogue between the stromal compartment and leukemic blasts can contribute to the onset of drug resistance and to identify metabolic targets to overcome it.

MISSIONS

The scientist will be involved in a highly collaborative project between the RESTORE (“Metabolic interplay and ageassociated loss of function”) and CRCT (“Onco metabolism and Drug Resistance in Acute Myeloid Leukemia”) teams. Using patient derived xenograft models wellhandled by the CRCT teamheaded by JeanEmmanuel Sarry, the candidate will behighly involved in the establishment of a precise cellular and metabolic mapping of stromal cells and AML blasts, not only in the bone marrow but also in several extramedullary organs. She/he will also be devoted to unravel the metabolic interactions existing between stromal cells including mesenchymal stromal cells and adipocytes, and blasts, and their role in the development of chemoresistance. Her/hiswork will be done in close collaboration with students and engineers working on the project, especially the bioinformatic engineer also recruited through the grant. General responsibilities include design, implement and interpret experiments, both independently and incollaboration, and communicate research and findings in a clear and concise manner. The candidate will present the progress of the project during bimonthly meetings between the two teams, as well asduringnationaland international conferences.

QUALIFICATIONS REQUIRED

  • A PhD degree preferably in biochemistry or cell biology and physiology
  • Expertise in the field of metabolism and stromal cell biology (in particular adipocytes and mesenchymal stromal cells) will be highly prioritized
  • Handson experience on in vivo (mice) experiments, confocal imaging, multicolor flow cytometry, oxygraphyand cell culture of mammalian primary cells
  • Experience in the interpretation of mass spectrometry data obtained from metabolomics and isotope (13Cmetabolites) tracing experiments is an asset
  • Knowledge in histology, quantitative PCR, and general lab protocols and methodologies used in the biological sciences
  • Computational expertise including experience with image analysis, FlowJo, Prism, and Excel. Mastery of R and Python would be a plus
  • High levels of initiative, autonomy and the ability to assume a high level of responsibility
  • Strong interpersonal and mentoring skills needed to effectively deal with students and people of the two collaborating groups
  • Good level in English is required as members of the teams are native English speakers

EMPLOYMENT

Starting on June2021, the job position is funded for 12months renewable twice.

The application should 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 (12 pages).

2. Curriculum vitae, including a description of relevant skills and experiences, as well as a full publication list.

3. Copy of PhD diploma.

4. Names, email addresses and telephone numbers to 23 references.

Apply before April 30th, 2021

CONTACT
Application should be sent to Audrey Carrière : audrey.carriere-pazat@inserm.fr and Isabelle Ader : isabelle.ader-perarnau@inserm.fr

PARTNER LABS

RESTORE Logo
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OUR tutorship