James A. Wells, along with fellow innovators Haian Fu of Emory University and Mary Ellen Digan of Novartis, are doing just that.
That seemingly simple overall sentiment has stemmed a robust career for Digan
, who has come at the question from different angles, vantage points and methods.
Trained as a Drosophila geneticist in molecular, cellular and developmental biology, she went on to work in the yeast, Pichia pastoris, on its genetics and protein expression before landing at the Novartis Institutes for Biomedical Research (NIBR).
"It is an exciting time not only for the understanding of basic biology but also for high-throughput screening where people are starting to move toward more complex cellular models," she
"Our understanding of all the previous years of work has built to where we're now able to work in a more complex world."
At the Center for Proteomic Chemistry
(CPC) at NIBR
designs screens and cell-based assays to discover low molecular weight inhibitors of different protein-protein interactions of therapeutic importance.
collaborates closely with all of NIBR's
departments, applying the suitable combination of lead finding approaches to each drug discovery project.
These include high- and medium-throughput screening, structural biology, fragment-based drug discovery, biophysics and various in silico approaches.
is the steward of the Novartis
Compound Bank, a collection of over one million chemical compounds.
In the SLAS Webinar, Digan
will share basic information on various methods to interrogate protein-protein interactions in cells and then hone in on specific examples from Novartis
will continue discussion of these methods with an in-depth example of assays employing BacMam, which uses viral insect particles to deliver and express genes in mammalian cells with minimum effort and toxicity.
"BacMam vectors don't replicate or integrate in mammalian cells so, in general, they are biosafety level 1," Digan states.
"That's really handy because screening labs are full of moving parts and people so if you can lower biosafety, that's good.
BacMam vectors also offer the ability to titrate expression and maximize sensitivity of BRET2 assays.
"It is my hope that cell biologists, or anyone interested in pathway biology or protein-protein interactions, will start to think about all of the things you can do with BRET2 and consider BacMam a versatile tool for many cell-based assays in addition to protein-protein interactions," Digan
Mary Ellen Digan, Ph.D.
Senior Research Investigator I
Center for Proteomic Chemistry