Anima Biotech is pioneering translation control therapeutics, a new class of drugs that specifically control protein translation as a novel strategy against hard and ‘undruggable’ targets in many diseases. Current programs are in Fibrosis, viral infections, oncology and Huntington’s disease. Anima has adapted the technology to high content screens, screening 100-200K libraries to identify translation modulators. A flexible and robust system is necessary to meet the current increasing demands in throughput. The final solution must meet the high-quality standards Anima demands of their screening assay.
Anima has developed a new method, Protein Synthesis Monitoring (PSM), which enables monitoring of the protein synthesis process, directly from the ribosomes inside cells, using fluorescent labeled tRNAs. In PSM, tRNAs labelled as FRET donors and acceptors are introduced into the cell. A FRET signal is generated when donor- and acceptor-labeled tRNAs come in close contact, as they do in active ribosomes. The intensity of the FRET signal correlates with the number of ribosomes containing the tRNA FRET pair, providing a cell-based assay for monitoring protein synthesis. PSM can monitor overall protein synthesis, using bulk tRNA, or the synthesis of a specific protein, using one or more specifically selected pairs of tRNA enriched in the protein’s sequence.
The PSM method was adapted for high throughput screening campaigns that consist of four separate stages. All stages are labor intensive with multiple incubation steps within the process, leading up to a long process time. The four separate stages are:
- Cell Seeding
- tRNA transfection
- Addition of compounds
- Fixation and Nuclei staining
Goals of the project
The main goal of the project is to have an automated solution, able to process up to 150 individual plates (384 well plates) per day. The first three stages of the total process will be included in the automation, the fourth and final stage will be performed separately from the automation.
The demands on the automated solution are:
- At least equal to current situation (outsourcing) in quality and throughput
- Flexible, increasing throughput demands in the future
- Robust, the solution must have low maintenance requirements and downtime
- Total integration of all the separate components, without manual intervention
- The system will be used dynamically, depending on workload
- Small footprint
The goal was to find a partner able to provide a single system containing all the equipment needed to run the assay flow through, according to the above specifications. Multiple vendors have been contacted, resulting in selection of the Bionex Hive platform.
Design of the solution
- BioNex Hive (including plate- and lid hotels and a HEPA filter)
- VWorks scheduling software
- BioNex BNX 1536
- Liconic STX 110 incubator
- Agilent Bravo
- Formulatrix Tempest
Result & conclusion
Anima Biotech has found a partner in GC biotech, who are able to create the right relationships and provide the correct resources to arrive at the final design of the solution, meeting all specified demands. The throughput demands are superseded with the current design to accommodate future needs.
Together with GC biotech, Anima biotech created a solution that increased the throughput to 150 plates per day, with room for growth. The method is broken up in the determined three stages, allowing Anima to approach their projects from a workload point of view and use the system as needed.
Results generated are equal in quality compared to the current situation. Detailed results of the experiments cannot be shown because of classified information.