Research objectives and content
Depending on environmental conditions, Schizosaccharomyces pombe can enter either pre-mitotic or premiotic DNA synthesis or remain in stationary phase. This decision point is called START. The MBF complex (pgsedololp72resllp73res2) is required for exit from START: it is responsible for the transcription of several genes necessary for entry into the S phase of the cell cycle. However the mechanisms that regulates the complex remain unknown. The main objective of this research project is to determine the contribution of the MBF complex to the cell cycle progression. Further, since cells lacking functional p85cdcl 0 or p73res2 are unable to undergo meiosis, we wish to determine the role of the components of the MBF complex in differentiation. In mamrnalian cells, the complex of the E2F/DP proteins induces the expression of several genes required for S-phase progression. In fact, the E2F/DP and the MBF complexes activate the expression of similar genes, such as ribonucleotide reductase and S-phase cyclins. Thus, even though they lack homology at the molecular level, they can be considered functional homologues. The E2F/DP complex is negatively regulated by the RB family of tumor suppressors. Loss of this regulation leads to premature cell cycle entry that may lead to tumor formation. The characterization of the molecular events that regulate S phase entry in a genetically manipulatable system such as S. pombe may lead to further insights into the regulation of this important cell cycle checkpoint in mammalian cells.
Training content (objective, benefit and expected impact)
During my Ph.D. in Barcelona University and my first postdoctoral experience at the Dana Farber Cancer Institute (Harvard Medical School) I have acquired a strong background in Biochemistry as well as in Molecular Biology. My goal now is to learn Cell Biology and Genetics of yeast, which will help me in the near future at the time of setting my own laboratory. And, to the best of my knowledge, this training can be best achieved at the laboratory of Paul Nurse, which is worldwide known for its excellence in the field of control of the cell cycle in yeast.
Links with industry / industrial relevance (22)