Russ Teichert and Drug Discovery at Scintillant Biosciences

Russ and his team at Scintillant Bioscience are experts in assays for therapeutics discovery and development.  Devinebio is proud to have them as a member of the Collective of Experts helping us uncover the therapeutics that treat Rare Disease. Russ has guided Scintillant to perform over 175 projects for 25 clients since company inception.

Here are some examples of their work:

Neurite Outgrowth Studies.  

Human iPSC-derived cortical neurons from wildtype vs patient-derived (mutant) iPSCs were plated at similar densities. Neurite outgrowth in the patient-derived variant was markedly reduced. Specifically, at a plating density of 2,500 cells/well in 96-well plates, the neurite extensions from the patient-derived neurons (test condition) were shorter and thinner when compared to wildtype iPSC-derived neurons (reference control). These results indicated that human iPSC-derived neurons can exhibit a defect in neurite outgrowth for genetic conditions causing neurodevelopmental disorders.

Wildtype iPSC-derived Neurons (reference control)

Patient iPSC-derived Neurons (test condition)

Inhibitor Screen for PARG.

DNA damage with methyl methanesulfonate (MMS) causes PAR polymerization which normally is cleared by PARG enzymatic activity.  Staining of PAR polymers allows the inhibition of PARG to be monitored. A test of 7 candidate PARG inhibitors as potential cancer therapeutics revealed compound #3 gave best response in two separate runs which allowed for robust determination of IC50 dosage.

Calcium Imaging in Neurons

Fluorescent reporter, Fura-2, can be used to monitor changes in cytosolic calcium concentration in neurons in response to a depolarization stimulus. In three replicates the response to stimulus was tested 3 times, which enabled measurement of baseline response.  Next, an inhibitor of voltage-gated ion channels was applied at three doses (low, medium and high) to allow the inhibitory activity on calcium release to be quantified.  This model system can easily be applied to quantify drug response in neurons derived from patient iPSCs or from primary neuronal cell cultures.

If you think these types of systems could be useful to you in your work, feel free to set a call at a time of your convenience, using the following scheduler:

 https://www.cloudhq.net/meeting/chris@devinebio.com