Early Stage Researcher - (3 years, renewable each year)

The INTEGRATA network –“Integrating chemical and biological approaches to target NAD production and signaling in cancer” – aims at providing a group of early stage researchers (ESRs) with a highly interdisciplinary and intersectoral training in drug discovery, focusing specifically on NAD production and on NAD/nucleotide signaling as targets for the development of new cancer therapeutics. INTEGRATA will train 14 PhD students in an overarching training programme involving training-by-research, joint courses of technical, scientific and transferrable skills, participation to public scientific events, and an intense intersectoral networking exchange plan (secondments). The INTEGRATA consortium encompasses academic institutions, research centers, and SMEs, all with proven experience in higher education and training, and state-of-the art scientific and technical expertise and infrastructures.

We are looking for an Early Stage Researcher for the Central Laboratory of Hematology - PhD fellowship in the Marie Sktodowska-Curie ITN European Training Network INTEGRATA on “Preclinical pharmacology studies with the discovered NAMPT inhibitors.”

DépartementDpt des laboratoires (DL)Code emploiAssistant Doctorant - 0131NiveauHors DECFODate d'entrée souhaitée03-06-2019Type de contratCDDCatégorie professionnelleMédico-techniquesLieuLausanneTaux d'activité100%Date de début de publication31-01-2019Date de fin de postulation28-02-2019Référence03887-MT-210-2019

Mission

The research activities implemented in INTEGRATA have the following objectives:

• To develop new agents for interfering with NAD biosynthesis in cancer cells [NAMPT, NAPRT, inhibitors and Ab drug conjugates (ADCs) to target NAMPT inhibitors to multiple myeloma (MM), B-cell lymphoma and AML cells], neutralizing monoclonal antibodies (mAb) against eNAMPT and eNAPRT and NAD/nucleotide signaling inhibitors (SIRT6, NUDT5, CD73, and TRPM2 inhibitors).


• To perform an extensive testing of the newly generated NAD biosynthesis and NAD/nucleotide-signaling inhibitors (and of inhibitors that have been recently developed by partners from the Consortium) in cultured cells and in in vivo cancer models, including models for assessing angiogenesis and cancer cells’ metastatic spread.


• To conduct pre-formulation/fingerprinting, formulation and pharmacokinetics (PK) studies with the newly produced NAD biosynthesis and NAD/nucleotide-signaling inhibitors.


• To define anticancer activity and potential toxicities of the newly generated agents, as well as of a dietary approach based on a NA-free diet w/ or w/o antibiotics (to reduce NAPRT activity) in relevant in vivo cancer models.

Each of the 14 ESRs will be enrolled in the PhD programme of the beneficiary’s organization (the beneficiaries which do not award PhD will establish agreements with local and international universities that can provide the degree) and will participate in the network’s training activities and work placements at the laboratories of the participating academic and industrial partners. In addition, the training programme of the recruited ESRs will be implemented with regular meetings and workshops within the INTEGRATA network.

The project offered by the University Hospital of Lausanne consists in conducting biochemical studies of the most active FK866 analogues (nicotinamide phosphoribosyltransferase/NAMPT inhibitors) already discovered) to determine their actual IC50s and using cell-based assays to determine their ability to induce apoptosis vs. autophagic cell death in acute myeloid leukemia, multiple myeloma, and B-cell lymphoma cell lines. Subsequent studies will be directed at defining the preclinical pharmacology profile of these molecule, including pre-formulation, formulation and PK studies (the latter to be conducted with up to four candidate NAMPT inhibitors). The aim shall be to identify NAMPT inhibitors with an improved PK profile compared to FK866 or CHS 828. Studies of biodistribution (NAMPT inhibitor concentration within xenografts of haematological malignancies) will be conducted with the candidate compounds. This programme will be completed by studies of anticancer activity of candidate new NAMPT inhibitors in AML, B-cell lymphoma and MM xenografts (including measurements of NAD levels in the xenografts). Since in vitro, a marked potentiation of FK866’s activity by the NAPRT inhibitor 2-HNA could be detected in numerous NAPRT-expressing AML and B-CLL samples (P4 and P1a), the selected, new NAMPT inhibitors will also be studied in combination with 2-HNA (a NAPRT inhibitor).

The ESR will be enrolled in the Doctoral School of the University of Lausanne.

Profil

• Master Degree or equivalent in biology


• A background in mammalian cell culture and animal (mouse) handling will be appreciated


• In case of equal qualification, candidates with background in cancer cell biology and highly motivated to work in an interdisciplinary group working at the interface of tumor microenvironment and metabolism will be preferred

Specific requirements :

Mobility eligibility requirement: The fellow must not have resided in the country where the research training activities will take place for more than 12 months in the 3 years immediately prior to the recruitment date (and not have carried out their main activity (work, studies, etc.) in that country).

Exceptions International Organisations: Eligible researchers must not have spent more than 12 months in the 3 years immediately prior to the date of selection in the same appointing international organisation.

Experience eligibility requirement: Eligible applicants must be in the first 4 years of their research careers (full-time equivalent research experience) at the signature of the contract (measured from the time the Master’s degree has been obtained)

Eligible applicants must not hold a PhD yet.

Contact et envoi de candidature

Please click on "Postuler" button to send the following documents until February 28th 2019

• an updated CV; the CV must be without gaps, in order to easily check the mobility and experience requirements. CVs that either do not clearly show the applicant’s past experience, or have gaps, will be considered ineligible.


• a letter giving reason for his/her motivation for the position;


• at least 1 reference letter (in English) from one former supervisor and/or lecturer;


• the scan of the degree (usually the Master Degree) which would formally entitle him/her to embark on a doctorate. In case the degree has not been obtained yet, it is necessary to send a declaration of the university stating that the degree will be obtained before the expected starting date;


• transcripts of records (document indicating their ranking and marks within their last year at their Master Degree as well as the courses/modules they have followed).

Applications must be in English.

For more information, please contact Dr. Aimable Nahimana, Research manager, Central Laboratory of Hematology : +41 21 314 42 58.