I will discuss recent results dealing with the assembly of the WASH complex in centrosomes and how WASH primes the formation of branched actin networks at the surface of endosomes through the uncapping of Dynactin.

Maintaining protein homeostasis (proteostasis) is key to resisting cellular stress and to promoting healthy aging and lifespan. Proteostasis is maintained by an integrated network of physiological mechanisms and stress response pathways that dynamically coordinate protein synthesis, folding, trafficking and degradation to regulate proteome content and quality. Recent studies have revealed that components of the proteostasis network play a critical role in regulating hematopoietic stem cell (HSC) maintenance and function during homeostasis and in response to stress. Strikingly, many of these pathways, despite being highly-conserved, exhibit exquisite cell-type specificity, and often function differently in HSCs than in restricted progenitors. In this seminar, I will present our data demonstrating that multiple components of the proteostasis network, including protein synthesis, protein degradation and the heat shock response, regulate multiple unique aspects of HSC biology, including their self-renewal potential, quiescence, regenerative activity and metabolism.

Drug resistance dissemination by horizontal gene transfer remains poorly understood at the cellular scale. Using live-cell microscopy, we reveal the dynamics of resistance acquisition by transfer of the F conjugative plasmid encoding the tetracycline-efflux pump TetA. We show that the entry of the ssDNA plasmid into the recipient cell is rapidly followed by complementary strand synthesis and expression of newly acquired genes. TetA production is enhanced by zygotic induction resulting in the optimized establishment of resistance. In the presence of protein synthesis-inhibiting antibiotics, acquisition of resistance becomes strictly dependent on AcrAB-TolC multidrug efflux pump. We demonstrate that AcrAB-TolC is required for maintenance of protein synthesis activity and therefore TetA production following plasmid acquisition. This work uncovers a novel essential role of multidrug efflux systems in the acquisition of drug-specific resistance by horizontal gene transfer and helps to understand the dissemination of antibiotic resistance in bacteria.