Postdoctoral Researcher in Computational Drug Design

PROJECT

This project aims at investigating machine-learning models able to identify drug-like molecules with previously unknown activity on a given cancer cell line. The most promising predictions will be experimentally validated by internal and external collaborators. The targets of the resulting phenotypic hits will be identified using existing molecular target prediction tools, including some developed in-house, to make an initial assessment of their efficacy and possible side-effects. A similar approach will be followed to identify synergetic drug combinations on a given cancer cell line. This project was funded by the competitive ANR Tremplin-ERC programme.

Further information (including how to apply): see PDF below

Master 2 Recherche "Oncologie" : Rôle de la synténine dans la progression de la leucémie

Responsable : Pascale Zimmermann – Encadrant : Raphael Leblanc

La Leucémie Myéloïde Aiguë (LAM) est liée à une prolifération anormale de blastes, des cellules hématopoïétiques devenues cancéreuses dans la moelle osseuse. Au sein de la niche leucémique, les cellules leucémiques et le micro-environnement interagissent de façon dynamique et bidirectionnelle afin de moduler la croissance et la survie de la LAM. Parmi les modes de communication intercellulaire, la sécrétion de nanovésicules, appelées exosomes, apparaît depuis quelques années comme un des acteurs majeurs de cette communication. Les exosomes permettent l’échange d’une information complexe entre les cellules qui influe grandement sur leur comportement. Bien que plusieurs études aient mis en évidence le rôle des exosomes dans la progression de la LAM, les mécanismes moléculaires associés restent peu connus. La synténine, une protéine intracellulaire découverte par notre laboratoire, contrôle la biologie d’une population d’exosomes. Elle est fortement exprimée au cours du développement précoce et ses niveaux protéiques sont anormalement élevés dans plusieurs types de cancers. Compte-tenu des évidences croissantes impliquant les exosomes dans la communication tumeur-micro-environnement, ce projet vise à clarifier le rôle méconnu de la synténine-tumorale dans la progression de la LAM, une maladie dans laquelle son rôle n'est ni étudié ni établi. La réalisation de ce projet permettra au candidat d’avoir un aperçu de l’expérimentation in vivo, mais surtout de se familiariser à différentes techniques in vitro de biologie moléculaire et cellulaire.

PhD thesis topic proposal: Ecole Doctorale 2017 - 2020 PhD fellowship call for applications

Form
Form

Title: Targeting of the PTK7 tyrosine kinase receptor in breast cancer

Despite undeniable therapeutic advances in recent decades, some breast cancers remain medical and scientific challenges. This is the case of triple negative breast cancers so called because of the lack of expression of HER2 and hormone receptors, making patients ineligible for targeted therapies. The search for therapeutic targets in these very aggressive cancers thus remains a priority.

The team of Jean-Paul Borg has shown that the PTK7 tyrosine kinase receptor belonging to the Wnt/planar cell polarity pathway is overexpressed in many cancers, including triple-negative breast cancers, and associated with poor prognosis and metastasis development. A characteristic of PTK7 is the absence of catalytic activity of its kinase domain, making the use of kinase inhibitors inaccessible. PTK7 is currently only targeted by an antibody-drug conjugate currently in early clinical development. This approach is interesting but does not clear PTK7 from the tumor cell. In this thesis project, the teams propose to target PTK7 by a recently described PROTAC (Proteolysis Targeting Chimera) approach promoting the degradation of proteins of interest by the proteasome. This technology has been shown to be effective in removing oncoproteins in tumor cells (BCR-ABL in acute myeloid leukemia). The project will consist first in the production and purification of the PTK7 kinase domain. Second, thanks to a screen of libraries developed by the Xavier Morelli/Yves Collette team expert in structural biology and chemistry and assays developed for drug design (isothermal titration calorimetry and thermal shift assay), the student will identify chemical compounds specific for PTK7 that will be functionalized to recruit an E3 ubiquitin ligase capable of degrading the receptor. Third, these compounds will be tested in vitro and in vivo using models of breast cancer cells developed at the CRCM.

Références de deux ou trois publications pour éclairer le doctorant sur le sujet proposé

Daulat A.M. and Borg J.-P. Wnt/Planar Cell Polarity signaling: new opportunities for cancer treatment. (2017) Trends in Cancer, 7: 113-125.

Lhoumeau A.-C., Arcangeli M.-L., Giordano M., Orsoni J.-C., Lembo F., Bardin F., Marchetto M., Aurrand-Lions M. and Borg J.-P. Ptk7 deficient mice have decreased hematopoietic stem cell pools as a result of deregulated proliferation and migration. (2016) J. Immunology, 196: 4367-77.

Lhoumeau A.-C., Prébet T., S. Martinez, and Borg J.-P. PTK7 tyrosine kinase receptor family. (2015) "The Receptor Tyrosine Kinase Handbook", Humana press 539-558.

Martinez S., Scerbo P., Giordano M., Daulat A.M., Lhoumeau A.-C., Thomé V., Kodjabachian L. and Borg J.-P. (2015) The PTK7 and ROR2 receptors interact in the vertebrate WNT/PCP pathway. J. Biol. Chem., 290: 30562-72.

Lhoumeau A.-C., Martinez S., Monges G., Castellano R., Poizat F., Saillard C., Viens P.,  Raoul J.-L., Prebet T.,  Aurrand-Lions M., Borg J.-P and Gonçalves A. Overexpression of the promigratory and prometastatic PTK7 receptor has an adverse clinical outcome in colorectal cancer. (2015) PLoS ONE, 10: e0123768.

Milhas S., et al. Protein-protein interaction inhibition (2P2I)-oriented chemical library accelerates hit discovery (2016). ACS Chem. Bio. Aug 19;11(8):2140-8.

Raux, B., et al. Exploring Selectivity of the First Bromo and Extra-Terminal (BET) Bromodomain Inhibition (2016). J.  Med. Chem. Feb 25;59(4):1634-41.

Basse, M.J., et al. 2P2Idb v2: update of a structural database dedicated to orthosteric modulation of protein–protein interactions (2016). Database Mar 15;2016. pii: baw007.

 

 The student will be involved in an interdisciplinary biology-chemistry program developed in close collaboration with academic (proteomics, drug design) and industrial (IPC drug discovery) platforms set up at CRCM and Institut Paoli-Calmettes.

Post-doctoral position in the Genome Dynamics and Recombination team

Applications are invited for a postdoctoral Research Fellow position based in the Cancer Research Centre of Marseille (CRCM), France, in the Genome Dynamics and Recombination team.

This is a 3 years ANR funded position to start during the first semester of 2017.

The CRCM is a one of the world's leading cancer research centre, located in the south of France. It combines basic, translational and clinical research at the heart of the Institute Paoli-Calmettes Cancer hospital in Marseille.

The appointed postdoc will be in charge to decipher the mechanism of Tel1/ATM-dependent control of meiotic DNA double-strand breaks formation in the yeast genetic model S. cerevisiae (Garcia et al, Nature 2015).The candidates must hold a PhD in molecular biology or relevant discipline and have an expertise or keen interest in the genome stability field. A previous experience in yeast genetics would be appreciated but is not mandatory, as excellence and motivation will be first criteria. Successful candidates will be self-motivated, enthousiastic, and able to perform/learn complex experiments.

Fluency in English and excellent communication skills (speaking and writing) are required.

To apply, please submit a copy of your CV (with contact information for three references) and a brief description of your research interests to  Valérie Garcia.

Deadline for application: January 31 st , 2017

 

 

    Ingénieur en biologie cellulaire et moléculaire

    L’ingénieur en techniques biologiques choisira, adaptera et mettra en œuvre les techniques de biologie dans le cadre des projets scientifiques de l’équipe de recherche. Sa mission principale sera la gestion des modèles animaux de l’équipe. Ce travail de recherche s’effectuera dans l’équipe de recherche du Dr. Patrice Dubreuil.

     

    Envoyer, lettre de motivation, C.V. et références à Patrice Dubreuil

      Offre de poste de post doc en bioinformatique de 18 mois

      Deadline 14 Novembre - voir version anglaise de l'annonce pour le détail du projet et des modalités de candidature

       

      Postdoctoral Researcher in Cancer Bioinformatics

      EMPLOYER Institut Paoli Calmettes

      FUNDED BY Cancéropôle PACA

      RESPONSIBLE TO Dr Pedro Ballester

      CONTRACT Full-time postdoctoral for 1.5 years in the first instance

      CLOSING DATE Monday 14 November 2016

      STARTING DATE January 2017

      Working environment The Cancer Research Center of Marseille (CRCM) is the basic science and translational research unit of the private cancer hospital Institut Paoli Calmettes (IPC). Also affiliated to INSERM, CNRS and Aix-Marseille University, the 270 researchers working at the CRCM form a strongly multi-disciplinary research environment characterized by frequent and close collaborations with IPC clinicians. IPC and CRCM form part of the comprehensive cancer centre Marseille SIRIC (http://www.siric-marseille.fr/Les-SIRICS.html). Further information available at http://crcm.marseille.inserm.fr/uploads/media/presentation_CRCM_2015_EN.pdf

      Project

      This project aims at identifying predictive markers of ex vivo drug sensitivity in Acute Myeloid Leukemia (AML). We have molecularly profiled over 100 AML tumours so far, each tested ex vivo against 73 selected drugs (150 new profiled tumours will be available to this project in the next two years). The successful candidate will investigate the application of a range of machine learning methods to predict which drugs are most effective for a given AML tumour exploiting in-house and public data resources. This research will require interacting closely with the oncologists, cancer biologists and in-house technological platforms acquiring and profiling these tumour samples (e.g. AML-specific somatic DNA mutations, cytogenetic features and methylation patterns in gene promoters). Occasional help with the primary and secondary analysis of molecular profiling data might be required. On the other hand, a number of publications are expected to arise soon from this project. Thus, the post holder is also expected to be proficient in writing this type of research for publication.

       

      Selection criteria –Essential  A PhD degree with a major focus on computational analysis of experimental data, preferably in an area directly relevant to the project.  Experienced in the application of machine learning to solve real-world problems in the context of biomedical research.  Skilled in the implementation of R or Python scripts for scientific data analysis.  Ability to undertake high quality scientific research as demonstrated by publications.  Ability to communicate effectively in English, both orally and in writing.

      Selection criteria – Desirable  A track record of publications in AML, modelling of cancer pharmacogenomics and/or biomarker discovery will be a strong advantage.  Experienced or trained in handling, integrating, processing and analysing NGS data (especially DNA-seq, RNA-seq and ChIP-seq).  Software engineering skills using C++, C and/or Python (numPy/SciPy/scikit-learn) including version control tools (e.g. git or mercurial).

      Working knowledge of open-source chemoinformatics toolkits (e.g. RDKit or OpenBabel) and medicinal chemistry databases (e.g. ChEMBL and ZINC).  Hands-on experience in the design and implementation of relational databases using MySQL and/or PostgreSQL as well as in web programming. What we offer The successful candidate will join the Ballester group at the CRCM. This is a recently created group, which will have nine members with the arrival of the post holder in January 2017 (group leader, three postdoctoral researchers, four PhD students and one master student). Thus, there will be opportunities for the post holder to collaborate with other team members. The post holder will receive a net monthly salary of €2,000. The contract will be for 1.5 years in the first instance, with possibility of extension. The successful candidate can be supported to apply for a permanent research scientist position (e.g. Inserm CR2 or CNRS CR2) to be held within the Ballester group. Currently, three CRCM candidates per year are successful in being awarded these permanent positions. In terms of quality of life, the CRCM is located in Marseille and thus the post holder will enjoy living in an exciting multi-cultural city right by the French Mediterranean coast.

       

      How to apply Candidates must send a CV including a list of peer-reviewed publications and a covering letter (maximum two pages) to pedro.ballester@inserm.fr with subject line “cancer bioinformatics position”. This letter will explain how they meet the essential selection criteria, which desirable selection criteria are also met and how this position would fit in their future career plans. This email must also state the names and emails of three scientists familiar with their research, who are willing to provide a reference. Please also mention in the letter where did you see this position advertised.

      PhD fellowships in cell and cancer biology

      The Cancer Research Center of Marseille (CRCM), France is pleased to announce that two PhD fellowships will be available from 1 January 2017 or as soon as possible thereafter. The application deadline is November 30th 2016.

       

      Applications are invited for the three-year fellowship from applicants who hold or expect to hold a master´s degree in a field relevant to the following PhD projects: A. PDZ-mediated syndecan-phosphoinositide networks in trafficking and signaling; B. PDZ network associated with Vangl and Scribble cell polarity proteins and implication in cancer.

       

      Project description

      PDZ proteins co-evolved with multicellularity and control various aspects of receptor signaling and trafficking, both known to be deregulated during cancer progression. The two present projects aim to address how PDZ-supported networks impact on cell-cell communication (including via exosomes), and on cell polarity. This work should contribute our understanding of the role of PDZ-networks in physiology and systemic diseases like cancer.

       

      Project A aims at providing a comprehensive map of interactions between syndecans, PDZ domain proteins and phospholipids, and investigating their role in subcellular membrane trafficking, exosome secretion and the signaling of various receptors (in part with Systasy).

       

      Project B aims at elucidating the role of PDZ interactions of Vangl on the trafficking of the receptor and thereby to gain fundamental insight into how Vangl trafficking is involved in breast cancer. We expect to develop peptide inhibitors of the PDZ domains of Scribble and establish the functional consequences of inhibiting the Vangl-Scribble interaction in cancer models.

       

      These PhD fellowships are part of the EU-funded project, PDZnet, which is an ambitious inter- and multidisciplinary European Training Network under the H2020 Marie Skłodowska-Curie Actions (www.pdznet.eu) offering training for 14 PhD fellows. The PDZnet consortium contains 12 different partners in 6 EU countries (Denmark, Sweden, Germany, France, Italy, Portugal). The PDZnet training program involves a range of network wide training activities.

       

      Required qualifications

      The successful candidate must:

      ·         hold a Master´s degree in a relevant subject area prior to the starting date

      ·         be fluent in English and have excellent communication skills

       

      Preferred qualifications

      We are looking for a highly motivated individual with a background in molecular, biochemical, cellular and/or cancer biology, ideally with some experience in microscopy, cell fractionation and/or exosome purification.

       

      Supervisors

      Project A. Prof Pascale ZIMMERMANN, pascale.zimmermann(at)inserm(dot)fr, Team ”Spatio-temporal regulation of cell signaling”

      Project B. Prof Jean-paul BORG, jean-paul.borg(at)inserm(dot)fr, Team “Cell polarity, signaling and cancer”

       

      General job description

      Your key tasks as a PhD fellow at Cancer Center of Marseille are to:

      ·         manage and carry through your research project

      ·         take PhD courses

      ·         write scientific articles and your PhD thesis

      ·         participate in national and international congresses and scientific meetings

      ·         stay at an external research institution, preferably abroad

      ·         teach and disseminate your research

       

      Key criteria for the assessment of applicants

      ·         Professional qualifications relevant to the PhD programme

      ·         Relevant work experience

      ·         Previous publications

      ·         The grade point average achieved

      ·         Other professional activities

      ·         Language skills

      ·         The successful applicant is also required to be enterprising and to possess good interpersonal skills

       

      Formal requirements

      The position is available for a three-year period for applicants holding a relevant master´s degree.

       

      The candidate should have less than 4 years of research experience and must not have resided or carried out his/her main activity in France for more than 12 months during the last 3 years immediately prior to the recruitment.

       

      The successful applicant will be requested to formally apply for enrolment as a PhD student at Aix-Marseille University.

       

      The PhD student is expected to be affiliated to the graduate programme of Aix-Marseille University.

       

      Questions

      For further information, applicants may contact the supervisors Pascale Zimmerman and/or Jean-Paul Borg.

       

      How to apply

      Send CV, motivation letter and the coordinates of 2 referees by email to Pascale Zimmerman and/or Jean-Paul Borg.

      Deadline for applications: 30 November 2016.

      An answer as to the granting of the fellowship can be expected approx. 4 weeks after application deadline.

       

      The Cancer Research Center of Marseille wishes to encourage everyone interested in this post to apply, regardless of personal background.

        Ingénieur en biologie cellulaire et moléculaire (Éq. Y. Collette)

        Conception et mise en œuvre des méthodes et technologies de biologie moléculaire, biochimie, et biologie cellulaire, associées aux projets de recherche de l’équipe de recherche des docteurs Yves COLLETTE et Xavier MORELLI. Cette équipe s’intéresse aux interactions protéiques en oncologie et à leur modulation par des petites molécules.

        Contact: Yves Collette

          Master & PhD Offers

          Join the Team "Homologous Recombination, NHEJ and Maintenance of Genomic Integrity"

          Our general interest is in deciphering the protein-DNA transactions at the heart of genomic integrity maintenance mechanisms – precisely, at the molecular level. We are addressing challenging questions about biological systems that can only be answered by multidisciplinary approaches.

          Whether your background is in biological or medical sciences, physics, nanotechnologies, materials engineering or computer science - whether you are a Master student (M2), a prospective Ph.D. student, a CR (Chargé de Recherche), IR (Ingénieur de Recherche) or are looking for a post-doctoral training, your creativity and ideas are of interest to us.

          We are applying for new research grants that could support you but we can also work together to try to get your own Fellowships at ARC, EMBO, HFSP, La Ligue contre le Cancer, European Commission or any other sponsor.

          Join the team "Molecular mechanisms of tumor cell migration"

          Masters 1 & 2 and PhD

          Masters 1 and Masters 2 students are welcome to join our team within the frame of the école doctorale des Sciences de la Vie et de la Santé of Aix-Marseille University. Students willing to pursue with a PhD thesis are invited to apply to the école doctorale for a fellowship.

          PhD students can also directly apply to join the lab at the thesis level, provided they pass the entry exam of the école doctorale and obtain a grant.

          Candidate post doctoral fellows are invited to contact the lab in order to write a proposal and submit a grant proposal.

          PostDoc Offers

          Two Funded Postdoctoral Positions in the team “Structure-Specific endonucleases and genome stability"

          Our laboratory focuses on understanding how structure-specific DNA endonucleases (SSEs) are controlled and how the SLX4 tumor suppressor contributes to genome stability in ways that rely or not on SSEs.

          Available projects will require extensive use of molecular biology techniques, cell culture work and will involve the development of cellular and biochemical functional assays.

          The successful candidates are expected to have obtained a Ph.D. in biology, biochemistry or related fields, published at least one first author publication in peer reviewed well established international journal and acquired training in the areas of DNA repair and/or cell-cycle control combined with solid experience in tissue culture and in cell biology and/or biochemistry.

          Funding is initially proposed for 12 months during which the candidate will be encouraged to apply for independent funding. Contingent upon job performance, we will offer an extension to the initial 12 months contract if no independent funding is obtained during the first year.

          Applicants should send a detailed CV, along with contact information of three references, to

          Join the team "Signaling, Hematopoiesis and Mechanism of Oncogenesis"

          We are looking for postdocs to join and lead our ongoing research projects. Our laboratory is studying protein tyrosine kinases as well as other therapeutic targets invoved in cell identity and cell transformation. The thematic of our research include hematological malignancies, melanoma, cell signaling, epigenetics, kinase inhibitors and, original mouse animal models derived in our laboratory.

          Our lab is staffed with senior and junior scientist, students and technicians. Whether a young or experienced postdoc, our lab and our Research Institute provide a favorable work environment to develop research projects.

          Patrice Dubreuil or Paulo de Sepulveda

          Join the Team "Homologous Recombination, NHEJ and Maintenance of Genomic Integrity"

          Our general interest is in deciphering the protein-DNA transactions at the heart of genomic integrity maintenance mechanisms – precisely, at the molecular level. We are addressing challenging questions about biological systems that can only be answered by multidisciplinary approaches.

          Whether your background is in biological or medical sciences, physics, nanotechnologies, materials engineering or computer science - whether you are a Master student (M2), a prospective Ph.D. student, a CR (Chargé de Recherche), IR (Ingénieur de Recherche) or are looking for a post-doctoral training, your creativity and ideas are of interest to us.

          We are applying for new research grants that could support you but we can also work together to try to get your own Fellowships at ARC, EMBO, HFSP, La Ligue contre le Cancer, European Commission or any other sponsor.

          Miscellaneous jobs

          No open position

          The CRCM is always searching for dedicated and motivated staff.

          Do not hesitate to contact us.