Bestämmande faktorer för effektiv syntes, veckning och målinriktning av proteiner i levande celler

Tidsperiod: 2020-01-01 till 2023-12-31

Projektledare: Magnus Johansson

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 3 520 000 SEK

Protein synthesis has been studied for decades, and we have a detailed picture of the process in vitro. However, when researchers aim to exploit the system, e.g. for recombinant protein production, or for the design of new antibiotic drugs, it becomes obvious that we have limited understanding of the dynamics of protein synthesis in its context, i.e. inside the busy crowded environment of the living cell. The aim of this project is to map the determinants of efficient protein synthesis, folding and targeting in living cells, and to study how these events are inhibited by antibiotic drugs. The project will be carried out primarily by a PhD student together with an experienced postdoc in the lab. To measure in vivo translation rates, we will develop new methodology based on our recently published system for live-cell single-molecule analysis of protein synthesis kinetics (years 1-2). Particularly, we will develop orthogonal translation systems to measure protein synthesis kinetics on defined mRNAs in an unperturbed cell background. Years 3-4 will then be devoted to data acquisition and refinement of quantitative models for protein synthesis dynamics. With an increasing demand for therapeutic proteins, such as monoclonal antibodies for cancer treatment, there is an urgent need for microbial-based systems for cost-effective production of recombinant proteins. With our unique experimental and analytical system, we have the opportunity and responsibility to aid in this development.