All Scientific Activities

Working with screening systems

Biological samples can be difficult to examine and compare due to the heterogeneous nature of cells and tissues. The effects of chemical compounds or drugs on the shape and behavior of cells can be very subtle. The “high content” imaging system enables rapid and reproducible acquisition of high-resolution images of cells after treatment with chemical compounds.

This process can be repeated thousands of times a day during a high-content screen. The basis of this technology is a fluorescent wide-field microscope coupled with a high-resolution confocal microscope. Using the confocal ability increases the image resolution from multi-layer specimens, such as complex tissue cultures or organoids.

Our screening systems, installed in 2017, is enabling higher precision measurements and visualization of fluorescently tagged proteins. 

The freedom of academic research

We get projects requiring high-throughput screening of small molecules from a wide variety of areas. This reflects the eclectic nature of projects that the team has been working on. While cancer-related projects still represent about 40% of the unit’s work-load, some projects relates to inflammation, neurodegeneration, metabolic disease, and other areas.

This is typical of an academic environment, where free and unencumbered thinking allows scientists to tackle interesting basic research questions underlying disease mechanisms. Such research would be prohibitive in a biotech or Pharma environment, which has more constrained goals related to marketing and production. This is one reason Pharma turns to academia for fresh ideas in areas of unmet medical need.

 

New: robotics

Investments in state-of-the-art instrumentation enabled a more productive workflow in the lab.
In 2017, the addition of a second Echo 555 liquid handler, based on acoustic dispensing technology, resulted in the doubling of our capacity to deliver compounds into microtiter plates for screening and follow-up work. As a result, compound screening can be performed with greater precision, either in one concentration or arrayed in dose response.

In addition, a new vial-handling robot will be installed soon to streamline incorporation of new compounds synthesized in medicinal chemistry.

Identifying proteins in breast cancer

High-throughput drug discovery involves testing tiny amounts of different chemical and biochemical compounds – out of the 100,000 such compounds in the lab’s library – to see if any interact with particular proteins or other biological materials. These tests can involve all of the compounds in the library or any subset, and automated assay equipment can test them all in short order.

Read More about Identifying proteins in breast cancer

Searching for NF-kB inhibitors

The NF-kB family of transcription factors (TFs) plays key roles in immune and stress responses and its deregulation contributes to several diseases. Therefore, its modulation has become an important therapeutic target.

As part of the collaboration with Prof. Rivka Dikstein from the department of bimolecular sciences, the Wohl Drug Discovery unit performed a high throughput screening (HTS) campaign against the G-INCPM compound library to identify compounds that inhibit the dimerization of the NF-kB protein p65.

Read More about Searching for NF-kB inhibitors