Objetivo
Cells growing in identical environments can display substantial phenotypic heterogeneity within a population. This is partly due to changes in genetic information that in turn cause systematic changes in expression rates. It has also recently been shown that even genetically identical cells behave differently because many cellular processes involve molecules present in small numbers which causes significant cell-to-cell fluctuations. Genetic and non-genetic sources of heterogeneity may be connected through fluctuations in DNA repair enzymes such as the RecBCD protein of Escherichia coli and its functional analogue AddAB in Bacillus subtilis. RecBCD/AddAB is essential for DNA double-strand breaks repair and stimulates genetic exchanges. It is expressed at low levels, thus raising the question of how bacterial cells cope with potentially large cell-to-cell fluctuations in this complex. The objective of the project is to characterize the single cell heterogeneity of DNA repair in bacteria and to evaluate its impact on cell survival. We will (i) quantify fluctuations in RecBCD protein. (ii) Manipulate fluctuation levels to measure their impact on cell survival. (iii) Interface the experimental analysis with mathematical modelling to gain a better understanding of the system. (iv) Test the generality of the system by applying the above analysis to AddAB in B. subtilis. The results will shed light on a crucial cell process where fluctuations are expected to be substantial for physiological reasons, and of great selective consequence. The project will be developed the laboratories of Prof. Paulsson (Systems Biology Department, Harvard Medical School, Boston USA) and Dr. Noirot (MICALIS institute, INRA, Jouy en Josas, France). It will give the opportunity to the applicant to be trained in a world leading group and to come back to develop her independent group in a major Systems Biology research laboratory in Europe.
Ámbito científico
Convocatoria de propuestas
FP7-PEOPLE-2009-IOF
Consulte otros proyectos de esta convocatoria
Régimen de financiación
MC-IOF - International Outgoing Fellowships (IOF)Coordinador
EH8 9YL Edinburgh
Reino Unido