about   CII home   shop   checkout
 
February 26, 2020
11 am to 12 pm EST
 
Biosensor Development Using CRISPR to Quantify Endogenous Protein Modulated by Targeted Protein Degraders  

 

Preview:

 
Webinar Description:

 

An assay platform that robustly and sensitively quantifies the kinetics of endogenous protein turnover is crucial for discovery of disease-relevant therapeutic agents. This need is particularly relevant for a new class of therapeutics known as targeted protein degraders. One example of such a molecule is the PROTAC, a bifunctional molecule that targets a specific disease-relevant protein for degradation by the cellular ubiquitin-proteasome system. The ideal platform should be sensitive, easy to use, and amenable to medium to high throughput screens.

In this webinar, we will describe how Eurofins DiscoverX has combined CRISPR/Cas9 technology with our well-established Enzyme Fragment Complementation (EFC) system in physiologically relevant cell backgrounds to quantify modulation of endogenous protein levels in response to therapeutic agents. To illustrate the approach, we will share a case study for development of biosensor cell lines in several cancer cell lines, including a blood cancer line, to study molecules that target BRD4. Inhibition of BRD4 with small molecules leads to reduction in c-Myc expression in several cancer models (MM and CML), and PROTACs targeting BRD4 have also shown promise in pre-clinical models. We will present results from several biosensor lines generated with a panel of PROTACs and small molecules that target BRD4. Comparison of data from the biosensor lines to a phenotypic assay (e.g. proliferation) will also be presented, and advantages of using an endogenous biosensor cell line over phenotypic readouts will be discussed.

Learning Objectives:

  • Strategy for biosensor development to quantify turnover of endogenous proteins
  • Performance of biosensor lines relative to phenotypic readouts
  • Ease-of-use and quantitative nature of biosensor

Speaker:

John Chevillet

Chao-Tsung Yang, Ph.D.
Principal Scientist, R&D Department
Eurofins DiscoverX

Dr. Yang obtained his doctoral degree of Developmental Genetics from Washington University School of Medicine and completed his post-doctoral training at immune response to bacterial infection at University of Washington. He started developing transgenetic tools using cutting-edge technologies at Janelia HHMI at Janelia Research Campus. Currently, he is a Principal Scientist at R&D DiscoverX Eurofins, leading genome engineering on cell assay development.

 

Cost: No Cost!