The Largest Maxprep Liquid Handler Installation Ever: Kigali Rwanda, 2022

“It was just a sea of Promega everywhere,” says Rebecca Roberts, a Promega Field Applications Scientist. “Floor to ceiling, piled up with Maxwell instruments, Maxprep Liquid Handlers, all the accessories and consumables…”

In her role on the Field Application Scientists team, Rebecca travels the United States installing the Maxprep Liquid Handler in customer labs and training scientists to operate the system and incorporate it into their workflow. This instrument automates the pre- and post-processing steps in a nucleic acid purification workflow. It’s a large and sophisticated instrument that takes up roughly four feet of lab bench space and weighs up to 220 pounds. It is intended for research use only, but during the COVID-19 pandemic, the Maxprep Liquid Handler, Maxwell RSC 48 Instrument, and several Maxwell purification kits were recommended for nucleic acid extraction protocols in the CDC 2019-Novel Coronavirus Real-Time RT-PCR Diagnostic Panel Emergency Use Authorization (EUA).  

When an instrument is sold, Rebecca and a Service Engineer spend three days on-site installing it and training a small group of staff to use it. One Maxprep instrument at a time is typical. On rare occasions, Rebecca might install two on a single trip. However, in 2022, Rebecca joined a multinational team of Promega scientists and engineers in Kigali, Rwanda for an order that was anything but typical.

Promega field applications scientists install a Maxprep Liquid Handler in a small room that already holds two more liquid handlers.
Field Application Scientists Rebecca Roberts, Ben Cooley and Lucy Swithenbank install a Maxprep Liquid Handler in Kigali, Rwanda

“We knew a large order from this customer was a possibility,” Rebecca says, “But I certainly wasn’t expecting an order of ten.”

This was the largest installation of Maxprep instruments Promega has ever seen from a single order. The customer also had a hard deadline that required delivery, installation and training to be complete in only six weeks – half the time usually quoted for a single instrument.

In the end, ten Maxprep instruments were installed at the National Reference Laboratory in Kigali, and more than twenty people were trained to use the systems for RNA extraction to support COVID-19 testing at a major international meeting. The order was a success, but that six week journey was a wild ride that depended on the hard work and dedication of Promega teams on both sides of the Atlantic.

And the impact of this work is still growing.

Continue reading “The Largest Maxprep Liquid Handler Installation Ever: Kigali Rwanda, 2022”

Targeted Protein Degradation: A Bright Future for Drug Discovery

targeted protein degradation and protacs

Our cells have evolved multiple mechanisms for “taking out the trash”—breaking down and disposing of cellular components that are defective, damaged or no longer required. Within a cell, these processes are balanced by the synthesis of new components, so that DNA, RNA and proteins are constantly undergoing turnover.

Proteins are degraded by two major components of the cellular machinery. The discovery of the lysosome in the mid-1950s provided considerable insight into the first of these degradation mechanisms for extracellular and cytosolic proteins. Over the next several decades, details of a second protein degradation mechanism emerged: the ubiquitin-proteasome system (UPS). Ubiquitin is a small, highly conserved polypeptide that is used to selectively tag proteins for degradation within the cell. Multiple ubiquitin tags are generally attached to a single targeted protein. This ill-fated, ubiquitinated protein is then recognized by the proteasome, a large protein complex with proteolytic activity. Ubiquitination is a multistep process, involving several specialized enzymes. The final step in the process is mediated by a family of ubiquitin ligases, known as E3.

Continue reading “Targeted Protein Degradation: A Bright Future for Drug Discovery”

Screening for Antiviral Compounds under Level 4 Containment Conditions

Working with bacteria and viruses that cause life-threatening diseases with no currently available treatment options takes guts. Most scientists are familiar with the routine requirements of good aseptic technique, are highly aware of laboratory safety requirements, and are more than familiar with autoclaves and sterilization issues, but if we make a mistake the consequences are usually only lost time or a spoiled experiment—not a lost life.

Scientists working with highly virulent organisms deal with a whole other level of risk that requires adherence to the strictest of safety regulations, and these containment regulations can sometimes place constraints on the type of experiment that can be performed with dangerous pathogens. A paper published in the April 2014 issue of Assay and Drug Development Technologies brought this to my attention and reminded me of the serious issues some scientists face on a daily basis as they research ways to combat infectious diseases.

Continue reading “Screening for Antiviral Compounds under Level 4 Containment Conditions”

Screening for Drug-Drug Interactions with PXR and CYP450 3A4 Activation

The pregnane X receptor (PXR) is a nuclear receptor known to regulate expression of cytochrome P450 (CYP450) drug-metabolizing enzymes (1). PXR has even been designated the “master xenosensor” due to its ability to upregulate cellular levels of a variety of drug-metabolizing enzymes in response to drugs and foreign chemicals. Elevated levels of CYP450 enzymes can elicit alterations in the pharmacokinetics of co-administered drugs, which can result in adverse drug-drug interactions (DDI) or diminished bioavailability. By assessing PXR activation and CYP450 enzyme induction early in the drug development process, many companies hope to reduce late-stage clinical failures and minimize the high costs associated with bringing a new drug to market.

Proportion of drugs metabolized by different CYPs

A paper by Shukla et al. (2) examined over 2,800 clinically used drugs for their ability to activate human PXR (hPXR) and rat PXR (rPXR), induce human cytochrome P450 3A4 enzyme (CYP3A4) at the cellular level, and bind hPXR at the protein level. Several studies have identified PXR as playing a key role in regulating the expression of CYP3A4, an enzyme involved in the metabolism of more than 50% of all drugs prescribed in humans. Since PXR activation and CYP3A4 induction have an impact on drug metabolism and pharmacokinetics, the authors wanted to obtain data that would be valuable in understanding structure-activity relationships (SARs), the connection between chemical structure and biological activity, when prioritizing new molecular entities (NMEs) for further in vitro and in vivo studies.

Continue reading “Screening for Drug-Drug Interactions with PXR and CYP450 3A4 Activation”