Metasensors · Metabolic sensor proteins that couple essential cellular processes and primary metabolism

Metabolic sensor proteins that couple essential cellular processes and primary metabolism

The large focus of METASENSORS is to understand the fundamental question of how essential bacterial cell processes are regulated at the protein level, in particular in response to metabolism. Within the last 20 years, bacteria have progressed from "bags of proteins" to "highly organized machines". It is now clear that bacterial processes including morphogenesis, division and chromosome dynamics are highly coordinated and involve molecular machines that are spatially and temporally regulated along the cell cycle. Along the same lines, these essential processes respond to metabolism because under different nutritional conditions, synthesis of precursors and macromolecules may vary. An emerging mechanism that cells employ to compensate these differences is to directly regulate the activity of key proteins involved in the cellular processes via so called metabolic sensor proteins. My research efforts are aimed at identifying and characterizing new regulatory proteins that either intrinsically participate in morphogenesis, division and chromosome dynamics or serve as metabolic sensor proteins coupling these processes to metabolism. In order to indentify these regulatory proteins, we have undertaken two complementary approaches: 1) a candidate approach to understand the function of the GluP rhomboid intramembrane protease. In general, rhomboids cleave their substrate within the membrane to activate proteins or signals. They are ubiquitous, play important biological functions in eukaryotes, yet their function is very poorly understood in bacteria. We used GluP as a model rhomboid in the Gram positive bacterium B. subtilis because it was initially described that GluP may be involved in both cell division and glucose transport. In departure from that report, our results support the idea that GluP is part of a complex degradation machinery in which it serves to destabilize membrane proteins, a mechanism akin to reticulum endoplasmic associated membrane protein degradation. In addition, that complex is likely involved in intracellular pH homeostasis. 2) a systematic genomic scale approach based on an innovative high-throughput fluorescence microscopy system. Mutant library screening at the "single-cell resolution" allowed us to identify 5 novel proteins involved in morphogenesis, cell division or chromosome dynamics. Some are necessary only under specific metabolic conditions. For example, our results support the idea that one protein participates in chromosome structure during slow DNA replication (slower metabolism). Furthermore, we provide evidence that the CmmB protein is a new cofactor of the essential cell-wall synthesis machinery. Thus, the characterization of these proteins significantly extends our understanding of several essential bacterial processes and how they respond to metabolic variations. The IRG fellowship has provided most of the funding required. Moreover, it allowed me to create a small team within a larger group. These stories will soon be the purpose of three articles (2015, 2016), obviously conditioning the possibilities offered for more independence in my career.

Data: CORDIS, © European Union