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

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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.

Looking for PhD candidates: Imaging cytoskeletal filament organization at the molecular scale

Looking for PhD candidates. Closing date April 10, 2017. "Imaging cytoskeletal filament organization at the molecular scale".

The project includes an internship in industry. Three-years-supported by the DOC2AMU program, Marie Skłodowska-Curie COFUND, A*MIDEX Foundation.

Cell division is a fundamental biological process that is essential for multiple aspects of animal physiology, including cell proliferation and differentiation, tissue growth and repair. Its dysfunction leads to several human pathologies, including tumour development and tissue degeneration. Cell division involves strong cell shape changes and thus heavily relies on the redistribution and cooperation of force-generating cytoskeletal filamentous proteins, notably actin filaments and microtubules. Little is known about the functional contribution of septins, a family of proteins which was recently recognized as a novel component of the animal cytoskeleton and which are essential for the successful completion of cell division. This project aims at developing optical and biological tools to decipher the organization of septins and their interaction with actin and microtubules during cell division. To this end, the student will implement dedicated optical imaging methods with the project co-supervisor at I. Fresnel with the goal to measure filament organization at high spatial resolution and potentially in real time. These measurements will be implemented using polarized fluorescence imaging, in which I. Fresnel has recognized expertise, on two systems: in vitro reconstituted cytoskeletal filaments from purified components, and dividing mammalian cells, with the cosupervisor at CRCM. In vitro studies will decipher the behaviour and local structure of single filaments and of filament assemblies, providing reference signatures for studies in cells. Functional studies in cells will then be performed at different stages of cell division. The molecular mechanisms at the origin of inter-filament organization will be investigated using septin mutants. The PhD student will work in co-supervision between Institut Fresnel (Doctoral School "Physics and Sciences of the Matter") and Centre de Recherche en Cancérologie de Marseille (CRCM) (Doctoral School "Health and Life Sciences"). The candidate is expected to be of biophysics background with knowledge in biology and a high interest in experimental optics. The work involving both optical instrumentation developments and biological sample preparation, the student will be involved in an interdisciplinary work where in vitro / cell sample developments, experimental imaging and data analysis will be equally important. A previous experience with interdisciplinarity during the master thesis is thus preferable, in particular involving optical microscopy. He/She should be motivated by the exploration of novel questions in biology. He/She should also be interested in the development of an instrument of interest for industry, since the detection device envisioned in this project can possibly lead to industrial development. The candidate will work for part of his/her time with an international collaborator and participate in several national and international conferences: he/she should therefore be capable of integration in international environments. To be eligible, the PhD candidate must not have resided or carried out their main activity (work, studies, etc.) in France for more than 12 months in the 3 years immediately prior to the start date (October 1st, 2017). For more information, please contact Sophie Brasselet (I. Fresnel) at sophie.brasselet@fresnel.fr or Pascal Verdier-Pinard (CRCM) at pascal.verdier-pinard@inserm.fr

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.