Integrated Calendar

How well are the changes in the levels of a protein over time explained by the changes in the corresponding mRNA? We compared the dynamics of 540 endogenously tagged proteins in human cancer cells to the dynamics of their mRNAs at high temporal resolution as the cells responded to an anti-cancer drug. We find dis-correlation, where most (65%) proteins show dynamics unrelated or even opposed to the dynamics of their mRNA. We next asked how post-transcriptional control, such as degradation or translation, might explain the observed protein dynamics. To address this we developed a novel non-perturbative method for measurements of protein degradation and translation rates called Bleach-chase. We find that the dis-correlation in the present condition is a result of two opposing global regulations: a time-dependent decrease in translation rates, and an increase in protein half-lives that is more pronounced the more stable the protein. The observed increase in half-life results primarily from reduced dilution due to cell growth-arrest. Overall, this study opens the way to understand how the dynamics of transcription, degradation and translation combine to produce proteome dynamics in living human cells.

``Population switching'' is a phenomenon involving a steep filling of a
narrow level in a quantum dot at the expense of a wide one as a common gate voltage is varied. This effect has been discussed in several contexts, including charge sensing by means of a current-carrying quantum point contact (QPC), as well as in relation with lapses of the transmission phase of a quantum dot. Is the switching involved abrupt, in which case one is facing a first order quantum phase transition? Mapping this problem onto a two-species Coulomb gas representation, we demonstrate that it is equivalent to an orbital Kondo model, and find that the switching is steep but continuous, in agreement with previous studies; however, when one tries to measure this behavior by electrostatically coupling one of the levels to a charge detecting QPC, one may render the switching abrupt. We show that this quantum phase transition is triggered by a change in physics from a Mahan exciton controlled dynamics to an Anderson orthogonality catastrophe controlled dynamics. Including the spin degree of freedom may lead to a realization of the SU(4) Kondo effect, as well as to quantum criticality of the two-impurity-Kondo type.