Montana Molecular - Signal Transduction & Covid-19 Research

Unique Fluorescent Biosensors Powering Basic Research on Cell Signaling in Health and Disease
NEW: Live-Cell Assays for COVID-19 Drug Screening

Benefits:

• Simple protocols, fast results, assays do not require specialized equipment or complex steps (e.g., the addition of an enzyme)
• Measure multiple second-messenger components of cell signaling pathways in real time and in relevant tissues & cell types
• Can be targeted to specific cells in mixed cultures or subcellular organelles
• Characterize signaling pathways activated by drugs, e.g., in pancreatic islets, neurons, cardiomyocytes, osteoblasts as well as in standard cell lines
• Multiplex GPCR Assays: Gs, Gq, Gi, Voltage
• Plate reader or microscope compatible – kinetics or dose response
• Benefits using the BacMam vector: controlled expression levels and low cell-to-cell variability, efficient expression in most mammalian cells including primary cells and iPSC cultures
• No cell lysis, single channel analysis, no FRET measurement (FRET based biosensors suffer from low signal-to-noise and usually are not compatible with automated plate reader detection)

"The best thing about Montana Molecular’s biosensors has been the ease of use"
(Vladlen Z. Slepak, PhD, University of Miami, School of Medicine)

Products:

COVID-19 Drug Screening / Pseudovirus Neutralization Assay

• Fluorescent SARS-CoV-2 cell entry assay based on two components: The first is a BacMam expression vector coding for human ACE2 to transform any cell into pseudo host cells. The second assay component is a SARS-CoV-2 Pseudovirus - a modified BacMam presenting the Spike protein on the surface of the BacMam capsid
• Identify therapeutic drugs that block Spike ACE2 binding
• No BSL-3 safety requirements
• Screen for neutralizing antibodies to SARS-CoV-2 spike and emerging spike variants
• BacMam is high-titer and more cost-effective to use than Lentivirus-based assays
• First cell based 3CLpro assay available on the market: Screen protease inhibitors in live cells; capture physiologically relevant dose response in living cells

GPCR Biology

• G-Protein Coupled Receptors (GPCRs) are one of the largest receptor families in the genome and are essential for the healthy function of nearly every organ in the body
• Detect kinetic Gs, Gi, and Gq mediated responses in living cells
• Combine multiple assays in the same cell population
• Express sensors and run assays in disease relevant cell types

Phosphodiesterase Biology

• Cyclic nucleotide phosphodiesterases (PDEs) are important drug targets with unique tissue distribution and functional properties
• This family of enzymes is key in the regulation of cyclic nucleotide second messenger levels because they degrade both cAMP and cGMP
• Detect changes in intracellular cAMP and cGMP
• Screen for PDE Inhibitors
• BacMam-mediated expression in disease relevant cell types

Cell Stress & Toxicity

• A robust, reversible biosensor for ER-stress and the Unfolded Protein Response (UPR)
• Ideal for use in primary cultures or iPSC-derived neurons or cardiomyocytes
• Combine with a red cADDis, GECO Ca2+, or DAG sensor to simultaneously monitor second messenger signaling

Neurodegeneration

• Examine ER stress, the UPR, and signaling biology in cells directly affected by neurodegenerative disease
• Identify and optimize therapeutic compounds and express mutant proteins related to neurodegeneration

Drug Discovery & Screening

• Optimize your leads, run second order screens, conduct SAR studies, and introduce drug targets to your cells
• Fluorescent assays and BacMam-packaged drug targets are powerful tools in the drug discovery process, particularly in secondary screens and lead optimization
• Single color, kinetic, fluorescence intensity-based assays (non-FRET) with high compatibility on fluorescent plate readers
• Capturing kinetic data in drug screening enables researchers to prioritize lead compounds by generating reliable metrics for potency, efficacy, partial and biased agonism

Optogenetics

Non-invasive manipulations of intracellular processes have recently appeared as an emerging research field. Now there are tools that enable you to use light to control cellular signaling as well as watch it. Montana Molecular provide an Optogenetic toolkit to optically elevate intracellular cAMP, measure changes in cAMP and calcium, and create excitable HEK cells.

Diabetes Research

• Gain insight into diabetes disease mechanisms and GLP-1 receptor pharmacology with bright fluorescent biosensor assays
• Examine biased agonism at the GLP-1 receptor in cell models and GPCR second messenger signaling in pancreatic islet cells

Custom BacMam Vectors

Many researchers are switching from plasmid transfection, stable cell lines and other viral vectors to using the BacMam system in their cells of choice because of its many benefits:

• BacMam is a BSL-1 modified baculovirus vector which efficiently transduces most mammalian cells – including primary cultures, cell lines, and iPSC derived cells
• BacMam has been used for years to transiently deliver target receptors, genetically-encoded biosensors and other constructs in cells of interest
• BacMam is silent in mammalian cells
• Consistent, titratable expression
• Simple workflow and versatility

iPSC-Derived Cell Assays

All Montana Molecular’s assays are compatible with use in iPSC-derived cells.

Resources