Host
Dr. Martin Turner
Babraham Institute, Cambridge
Duration 36 months
 
Molecular mechanisms of selection in the germinal center
 
Background
The fundamental biology of the germinal center (GC) reaction, which is one focus of the COSMIC Consortium, underpins pathologies including B-cell neoplasia and rheumatoid arthritis, which are the disease focus areas of COSMIC.  It is the goal of the Turner lab to understand the molecular mechanisms that promote the positive selection of B cells in the GC.  By using mouse models we can identify rare positively selected cells and profile their gene expression programmes.  The effects of specific gene mutations on positive selection and on gene expression can then be used to identify pathways and mechanisms. We are particularly interested in how gene expression is regulated through alternative RNA processing mechanisms, such as alternative splicing and polyadenylation.  The PhD candidate will apply state of the art next generation sequencing technologies (e.g. Oxford Nanopore sequencing) to identify changes in alternative splicing and polyadenylation that occur in B cells in response to positive selection signals. By using mutant mouse models (see references below) they will gain a deeper insight into how T cell help is interpreted by B cells and how these processes may lead to disease. 

Selected Reading:
Monzón-Casanova E., Screen M., Diaz-Munoz M.D., Bell S.E., Lamers G., Curk T., Ule J., Solimena M., Black D.L., Smith C. and Turner M. (2018) The RNA binding protein PTBP1 is necessary for B cell selection in germinal centres. Nature Immunology (In press).
Diaz-Muñoz., M. D., Bell, S.E., Fairfax, K., Monzon-Casanova, E., Cunningham, A.F. Gonzalez-Porta, M., Andrews, S.R., Bunik, V. I., Zarnack, K., Curk, T., Ward A. Heggermont, W.A., Heymans, S., Gibson, G.E., Kontoyiannis, D. L., Ule, J., and TurnerM.  (2015) HuR-dependent regulation of mRNA splicing is essential for the B cell antibody response. Nature Immunology (4):415-25. PMID: 25706746
 
Our Department
The laboratory of Lymphocyte Signaling and Development has a long history of contribution to our understanding of mechanistic insights into lymphocyte biology. 
The Turner group has strengths in the understanding of gene expression regulation including the integration of signaling with transcriptional and post-transcriptional regulatory mechanisms.  We provide an excellent training environment for ESRs who will be member of the University of Cambridge.
 
Your experience
  • A Master’s degree or equivalent in Molecular biology or Immunology. 
  • A desire to learn experimental and computational approaches
  • Excellent higher education track record 
  • Fluent spoken and written English skills
  • Outstanding communication skills
  • Well-developed critical thinking skills
Our offer
This 3-year position is funded by the Marie Skłodowska-Curie actions of the European Union's Horizon 2020 research and innovation programme under grant agreement No 765158. The student will be registered for the PhD degree at the University of Cambridge. 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. You can apply using the online application form. For more information about the position you can contact Dr. Martin Turner.

 

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