Establishment of a hyper-secreting eukaryotic protein production system as alternative cell factory for biotherapeutics.

This project is offered within the framework of the International PhD Program „Biomolecular Technology of Proteins – BioToP” at BOKU - University of Natural Resources and Life Sciences, Vienna, Austria.

Project description

Recombinant therapeutic proteins are currently produced primarily in mammalian cell factories, specifically in Chinese Hamster Ovary cells. These cells, while highly flexible and able to produce safe and high quality proteins, also have a number of disadvantages. These include high genomic and phenotypic variation, instability of production, secretory bottlenecks and interclonal variation. These problems are not likely to be overcome by switching to any other mammalian cell system, as inherently, due to their large genomes and complex regulatory networks, these have the same issues of genomic instability and phenotypic variation.

The aim of this project is to evaluate different organisms and cell lines that might be used to replace current mammalian cell factories. The initial task will be to determine the maximum protein secretion rate of existing cell lines and cell factories as a quantitative background measure to evaluate novel candidates. In subsequent work, we will look into the mechanism underlying the higher yield of secreted protein in the best candidates: be it higher translation rates, better assembly or more efficient vesicular transport.
Subsequently, novel organisms and cell types will be evaluated for their potential as cell factories. Organisms of interest include insects, protists and small marine organisms. Selected candidates will be screened for natural protein secretion and then tested for maximum achievable transient protein secretion. Promising candidates will be further evaluated for growth, final cell density, available culture media, genome size, available selection systems and DNA transfectability.

The final outcome will be a list of candidate cell lines or organisms with optimized media, defined protocols for DNA transfection and an optimized selection system (if necessary engineered into the cells).

Required skills and qualifications

We are looking for a graduate student with a Master´s degree in Life Sciences, preferentially with experience in microbiology or cell culture and molecular biology.

For more detailed information about the project and the PhD program BioToP please visit http://biotop.boku.ac.at

Application

The PhD Program BioToP will only consider applications that are submitted using the official BioToP application forms. No other forms of applications will be accepted.

For application guidelines and download of forms please visit http://biotop.boku.ac.at.

Application Deadline: 09.01.2017