Host
Dr. Kostas Stamatopoulos / Dr. Anastasia Hadzidimitriou
Institute of Applied Biosciences | INAB (http://inab.certh.gr)
Centre for Research and Technology Hellas | CERTH (http://certh.gr)
6th km Charilaou-Thermis, 57001 Thermi, Thessaloniki
Greece
Duration 36 months
 
Functional implications of affinity maturation for the ontogeny and evolution of B cell lymphomas through combined NGS immunogenetics and 3D analysis
 
Background
B cell non-Hodgkin lymphomas (B-NHL) comprise a heterogeneous group of tumors deriving from the neoplastic transformation of mature, differentiated B cells. Therefore, not paradoxically, the neoplastic cells retain several attributes of their normal counterparts, including the dependence on microenvironmental stimuli for their survival and proliferation. In normal B cells, such stimuli are delivered through various receptors, amongst which perhaps the most critical role is played by the B cell receptor (BcR), a a multimeric complex composed of surface immunoglobulin (sIG) and the noncovalently bound heterodimer Igα/Igβ (CD79a/CD79b). The IG mediates the recognition of and selection by specific antigen(s) that orchestrates the maturation and terminal differentiation of B cells.
Interestingly, the BcR IG is also retained in the majority of mature B-NHL with ample evidence suggesting indicating that B cell lymphomagenesis may represent the trade-off for antigen-induced stimulation and proliferation of mature B cells at different stages along their differentiation pathway, critically including the germinal center (GC) reaction, which is the focus of the COSMIC Consortium.
The PhD candidate at CERTH will employ high-throughput immunoprofiling of the BcR IG gene repertoire from different types of BCL of different postulated cell(s) of origin, focusing on chronic lymphocytic leukemia (CLL), mantle cell diffuse large B cell lymphoma and splenic marginal-zone lymphoma. Particular attention will be given also to pre-lymphomatous conditions and/or early stages of BCL (e.g. CLL-like monoclonal B lymphocytosis, in situ follicular neoplasia, clonal lymphocytosis of marginal-zone origin). These studies will be complemented by structural analysis for assessing and/or predicting in silico (3D models) the impact of somatic hypermutation (SHM) occurring as part of the GC reaction on IG structure, especially focusing on the relevance of synergistic (closely positioned) SHMs and on building the “ancestor” IG sequence-molecule (reconstructing immune lineages in BCL). Finally, in selected cases, actual crystals of recombinant clonotypic BcR IG from different lymphomas will be investigated to explore whether higher-order clustering based on immunogenetic profiles is possible in BCL.
 
Our research team
INAB | CERTH is specializing in the immunogenetic study of the BcR IG using high throughput sequencing technologies, focusing on diversity, sequence and structural patterns, in different clinical scenarios, ranging from infections to autoimmunity, allergy and, particularly, mature BCL.
More recently, INAB | CERTH has been active in characterizing BcR IG 3D structures in B cell lymphomas through integrated crystallographic and biochemical analysis, revealing novel processes underlying their development and evolution.
 
Your experience
  • Candidates should have a Master’s degree or equivalent in Molecular biology, or Immunology. 
  • Excellent higher education track record and strong scientific curiosity.
  • Fluent spoken and written English skills
We seek a highly motivated scientist who enjoys an interdisciplinary environment and an interdisciplinary project, able to work independently but also as part of a team.
 
Our offer
This 3-year PhD position is funded by the  Marie Skłodowska-Curie actions of the European Union's Horizon 2020 research and innovation program under grant agreement No 765158.  You will be appointed as fulltime PhD for 3 years with INAB | CERTH and the affiliated Aristotle University of Thessaloniki, Thessaloniki, Greece. Under recruitment procedure the general MC salary description is detailed. Due to local law and differences in family situation, the exact salary will be determined in the host institution upon recruitment.
 
Your application
See recruitment procedure. However, due to the fact this is the last position availble, you can must apply directly to Dr. Kostas Stamatopoulos (kostas.stamatopoulos@certh.gr) AND (in cc) our project manager Dr. Laurian Jongejan (l.zuidmeer@amc.uva.nl)! Clearly indicate in the mail how many years of research experience you have had since your last (MD/Masters) degree, and if and for how long you have worked in Greece in the past 3 years (when applicable). Deadline: 10th of September 2018!
 
For more information about the position you can contact Dr. Kostas Stamatopoulos (kostas.stamatopoulos@certh.gr, +30.2310.498271) or Dr. Anastasia Hadzidimitriou (achatzidimitriou@certh.gr, +30.2310.498474).
 
INAB | CERTH
The Institute of Applied Biosciences (INAB) at CERTH, the Centre for Research and Technology Hellas (CERTH), is the flagship Institute for Biomolecular research in Northern Greece, one of the four nodes of the Greek Precision Medicine Network. Its mission is to carry out basic and applied research in the fields of Molecular Medicine and Bioinformatics. Also relevant to mention, CERTH has a mission to implement horizontal actions related to Researchers Career & Mobility in Greece and the ERA. Inline to these objectives, CERTH is represented in relevant European Networks: (i) Euraxess - Researchers in Motion Network: CERTH is the coordinator of the Greek Euraxess Network; (ii) Horizon 2020 Marie Skłodowska-Curie Actions: CERTH is the National Contact Point for Marie Skłodowska-Curie Actions.

 

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