A bioassay is an analytical method to determine the concentration or potency of a substance by examining its effect on living cells or tissues. In the field of drug discovery, screening assays are performed to discover compounds with a specific biological activity, such as an enzyme or a transporting protein with an inhibitory or activating effect on a certain biological system. For example, in the Screening, Profiling and Analytical Facility (SPAF) of the NCCR TransCure, we performed a screening assay to find small-molecule inhibitors of a cellular sodium channel called TRPM4. We assessed the activity of TRPM4 in vitro by generating a recombinant cell line expressing TRPM4. The cells of the assay, loaded with a fluorescent dye specific for sodium, expressed a fluorescent signal that was recorded in real-time on our FLIPR Tetra fluorimeter. Using this assay, we explored dose-response relationships of the inhibitors to TRPM4. The same assay was then used for a larger screening of more than 8,000 compounds at Novartis in Basel. The resulting hits were subsequently validated at the SPAF and the new tool compounds will be used to further characterise TRPM4 e.g., by electrophysiology.

Another type of screening assay is used to find individuals in a population who have antibodies against a certain virus. The recent COVID-19 outbreak can be taken as an example. In this case, a general strategy is to incubate immobilised virus proteins with the serum of the individuals and, following several washing steps, to detect the specific binding of the antibodies from the serum to the virus proteins. Using such an approach, it is possible to find individuals who were in contact with the virus causing COVID-19.

Simon Singer
NCCR TransCure technician (Gertsch group)