Research

The endoplasmic reticulum (ER) is the key organelle for folding and processing of secretory proteins. Inefficient folding and secretion are a major challenge in production of recombinant proteins needed as biopharmaceuticals or for securing future food requirements. In most non-mammalian cells, the ER is spatially limiting these processes. SynthER aims to go beyond mere physical ER expansion by tailoring functionality through orthogonal and combinatorial expression of synthetic ER shaping proteins in yeast and plant cells. Inspired by professional secretory mammalian cells, SynthER envisages to biomimic their ER architecture in yeast and plants. The new morphologies will be monitored by a wide range of microscopic methods and quantitative image analyses, and their impact on the quality and quantity of secreted recombinant proteins will be determined. Furthermore, synthetic ER exit vesicles (SERV) will be designed to deliver their protein cargo directly to the plasma membrane, bypassing the often adverse functions of the Golgi and vacuole. SERVs shall be programmable synthetic circuits, that can be expressed on demand. Taken together, SynthER will develop novel cell factory concepts that represent a significant advance to the state of the art. Synthetic endomembrane engineering addresses a timely research topic through a pioneering synthetic biology approach with significant potential for advancing both the scientific understanding of secretory pathway plasticity and impacting technological applications, thus benefiting medicine and biotechnology. Our ground-breaking interdisciplinary combination of cross-kingdom molecular and cell biology in microbes and whole plants together with advanced microscopy and engineering unlocks new scientific opportunities and expands the toolkit of synthetic cellular design.

Upcycling is the process of transforming by-products or waste materials into new materials or products of greater quality. In its mission towards a circular bioeconomy, the PhD project PectiUp - funded by the Christian Doppler Research Association under the thematic call "Energy transition and Circular economy" - will develop strategies, technological innovations and microbial (yeast) strains for transforming food-industry waste into value-added proteins required in food production.

Microbial cell factories like specialized bacteria, yeast and fungi, are used to produce relevant compounds and engineered biomolecules such as commodities, fine chemicals, food ingredients and biopharmaceuticals. Tailor-made robust microorganisms displaying novel biological behaviors produce these products in a non-chemical way utilizing nature’s toolset, in general using renewable inputs such as glucose or industrial side streams. C1 feedstocks, such as methane, methanol, formate, CO2 and CO, have important advantages over traditional organic carbon sources like glucose. They are cheap, can be obtained from CO2 in a renewable way, do not compete as food or animal feed and do not require extensive pre-processing from complex agricultural side-streams. Implementing C1 substrates in microbial cell factories would ensure a circular carbon economy that is inherently sustainable. However, due to the relative novelty of this approach, further work will be required to have abiotic C1 substrates compete with biological feedstocks. The CiTrY project will contribute to this goal by investigating and improving transport mechanisms of the C1 substrates over outer and organelle membranes of the microbial cell factories. Underexplored proteins and proteins families will be investigated, advanced protein engineering strategies and high-throughput screening will be conducted, and a novel organelle membrane targeting approach will be developed.