Protein homeostasis embodies a delicate balance between protein synthesis and breakdown, representing the dynamic cycle of protein “life and death.” About one-third of newly formed proteins undergo degradation. Consequently, the processes of protein translation and turnover are rigorously controlled to uphold cellular function and viability. Hence, regulating protein homeostasis in reaction to environmental cues has become a crucial strategy to manage disturbances spanning from aging to pathological conditions in both animals and plants. To allow rapid, versatile, and cost-efficient responses to sudden environmental changes, eukaryotes utilize reversible translational arrest caused by compartmentalization of transcripts in cytosolic membraneless aggregates formed by phase separation. One such type of aggregates are processing bodies (PBs), dynamic ribonucleoprotein aggregates conserved among eukaryotes. PBs are involved in translational arrest, mRNA decay and both RNA and protein quality control and regulate several developmental processes and responses to abiotic stresses. However, our knowledge of how and under which conditions PBs are formed as well as if PBs are hijacked by pathogens to manipulate protein translation is unknown.
Our team aims to delve deeper into how pathogens disrupt this mechanism. Through the generous support of approximately 565,000 euros from the Boehringer Ingelheim Foundation, as part of the “Rise Up!” funding program, the project is set to commence on August 1, 2024, and span a duration of three years.
Human pathogens like salmonella or legionella, as well as viruses, have been demonstrated to impact protein synthesis. Initial investigations led the Üstün lab indicate that plant pathogenic bacteria similarly influence protein synthesis, with this alteration being implicated in disease progression. In our upcoming project titled “Manipulation of protein translation as a virulence strategy of pathogenic bacteria,” we aim to further explore this phenomenon. To this end we have advertised a Postdoc and a PhD position. The postdoc will focus on how PBs are hijacked by bacterial infection to alter global protein translation and what mRNAs are sequestered and repressed in translation. The PhD candidate will address how bacterial effectors induce the formation of PBs to understand the mechanism of PB assembly and analyse the composition of PBs during infection. More details about the positions, requirements and deadlines for application can be found in the job adverts. Apply if you are interested in proteostasis and would like to work in an international, innovative and inclusive team!
All in all, through this endeavor, we anticipate elucidating the comprehensive understanding of how proteostasis, specifically at the level of protein translation, governs immune responses and is consequently manipulated by pathogenic bacteria. Grasping the underlying molecular intricacies of translation modulation in disease settings will pave the way for innovative approaches to tackling diseases and environmental adversities.
